Seamless Phase I/II Study of Stereotactic Lung Radiotherapy (SBRT) for Early Stage, Centrally Located, Non-Small Cell Lung Cancer (NSCLC) in Medically Inoperable Patients
OBJECTIVES:
Primary
- To determine the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT)
in medically inoperable patients with centrally located stage I non-small cell lung
cancer. (Phase I)
- To estimate the local control rate of SBRT at the MTD in these patients. (Phase II)
Secondary
- To estimate the rates of adverse events (other than dose-limiting toxicity) of ≥ grade 3
that is possibly, probably, or definitely related to treatment and that occurs within 1
year after the start of SBRT in these patients.
- To estimate the rates of late adverse events (i.e., occurs > 1 year after the start of
SBRT) in these patients.
- To estimate the local control and progression-free and overall survival rates in
patients treated with this regimen.
OUTLINE: This is a multicenter study.
Patients undergo stereotactic body radiotherapy every 2 days over 1½-2 weeks [total of 5
fractions (FX)] in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed every 3 months for 2 years, then
every 6 months for 2 years, then annually.
A Phase III Study of Postoperative Radiation Therapy (IMRT) +/- Cetuximab for Locally-Advanced Resected Head and Neck Cancer
OBJECTIVES:
Primary
- Determine whether the addition of cetuximab to postoperative intensity-modulated
radiotherapy (IMRT) will improve overall survival (OS) in patients with locally advanced
squamous cell carcinoma of the head and neck at intermediate risk following surgery.
Secondary
- Assess the impact of the addition of cetuximab to postoperative IMRT on disease-free
survival (DFS) of these patients.
- Assess the impact of the addition of cetuximab to postoperative IMRT on acute and late
dysphagia, xerostomia, skin toxicity, and other toxicities according to common Toxicity
Criteria for Adverse Effects (CTCAE), v. 4 and their relationships with patient-reported
outcomes at 3, 12, and 24 months.
- Analyze tumor for epidermal growth factor receptor (EGFR), specifically the extent of
EGFR overexpression by immuno-histochemistry (IHC) and FISH analysis, EGFRvIII
expression, as well as the association of these assay data with OS and DFS.
- Analyze tumor for human papillomavirus (HPV) infection (as defined by in situ
hybridization), specifically, within the cohort of patients with oropharynx cancer, to
perform an exploratory analysis of the impact of HPV on DFS and OS of this patient
subset.
- Analyze tumor DNA for TP53 mutations as a predictor of response to cetuximab and
prognosis.
- Analyze germline DNA of polymorphic variants in EGFR intron repeats as a predictor of
response to cetuximab.
Tertiary
- Assess the impact of the addition of cetuximab to postoperative IMRT on loco-regional
control.
- Assess the impact of the addition of cetuximab to postoperative IMRT on patient-reported
quality of life, swallowing, xerostomia, and skin toxicity based on head and neck
specific instruments, including the Performance Status Scale for Head and Neck Cancer
(PSS-HN), the Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N), the
University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS), and the
Dermatology Life Quality Index (DLQI).
- Assess the impact of the addition of cetuximab to postoperative IMRT on cost-utility
analysis using the EuroQol (EQ-5D).
- Evaluate the utility of image-guided radiotherapy (IGRT) as a means of enhancing the
efficacy (i.e., loco-regional control) of IMRT while reducing the acute and/or late
toxicity (particularly xerostomia) and improving patient-reported outcomes (particularly
XeQOLS scores).
- Retrospectively compare the loco-regional control rate in patients treated with IMRT
alone (no IGRT or cetuximab) with similar patients treated with external beam
radiotherapy alone in the postoperative clinical trial Radiation Therapy Oncology Group
(RTOG)-95 01.
OUTLINE: This is a multicenter study. Patients are stratified according to clinical stage
(T2-3 vs T4a), EGFR expression (high [≥ 80% of cells staining positive] vs low [< 80% of
cells staining positive] vs not evaluable), primary site of disease (oral cavity vs larynx vs
oropharynx p16+ vs oropharynx p16- vs oropharynx, p16 not evaluable), and use of image-guided
radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week
for 6 weeks in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients undergo IMRT as in arm I. Patients also receive cetuximab IV over 1-2
hours once weekly beginning at least 5 days prior to the start of IMRT and continuing
for 4 weeks after the completion of IMRT (for a total of 11 doses) in the absence of
disease progression or unacceptable toxicity.
Quality of life is assessed at baseline and at 3, 12, and 24 months.
Tissue samples are collected periodically for further laboratory analysis.
After completion of study treatment, patients are followed up at 1 and 3 months, every 3
months for 2 years, every 6 months for 3 years, and then annually thereafter.
A Phase III Trial of Accelerated Whole Breast Irradiation With Hypofractionation Plus Concurrent Boost Versus Standard Whole Breast Irradiation Plus Sequential Boost for Early-Stage Breast Cancer
OBJECTIVES:
Primary
- To determine whether an accelerated course of hypofractionated whole-breast irradiation
(WBI) including a concomitant boost to the tumor bed in 15 fractions following
lumpectomy will prove to be non-inferior in local control to a regimen of standard WBI
with a sequential boost following lumpectomy for early-stage breast cancer patients.
Secondary
- To determine whether breast-related symptoms and cosmesis from accelerated WBI that is
hypofractionated (in only 3 weeks) with a concomitant boost is non-inferior to standard
WBI with sequential boost.
- To determine whether the risk of late cardiac toxicity in patients with left-sided
breast cancer treated with hypofractionation will be non-inferior to conventional
fractionated radiation therapy (RT) based upon analysis of radiation dosimetry from
CT-based treatment planning and normal tissue complication probability (NTCP)
calculations.
- To determine whether CT-based conformal methods intensity-modulated radiation therapy
(IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for WBI are feasible in a
multi-institutional setting following lumpectomy in early-stage breast cancer patients
and whether dose-volume analyses can be established to assess treatment adequacy and
likelihood of toxicity.
- To determine that cosmetic results and breast-related symptoms 3 years after
hypofractionated breast radiation with concomitant boost will not be inferior to that
obtained 3 years after WBI with sequential boost.
- To determine whether future correlative studies can identify individual gene expressions
and biological host factors associated with toxicity and/or local recurrence from
standard and hypofractionated WBI.
- If shown to be non-inferior, to then determine if accelerated course of hypofractionated
WBI including a concomitant boost to the tumor bed in 15 fractions following lumpectomy
will prove to be superior in local control to a regimen of standard WBI with a
sequential boost following lumpectomy for early-stage breast cancer patients.
- To determine whether treatment costs for hypofractionated WBI with concomitant boost are
not higher than WBI with sequential boost.
OUTLINE: This is a multicenter study. Patients are stratified according to age (< 50 vs. ≥ 50
years), prior chemotherapy (yes vs. no), estrogen-receptor status (+ vs. -), and histology
grade (1-2 vs. 3). Patients are randomized to 1 of 2 treatment arms. Treatment begins within
9 weeks of last surgery or chemotherapy delivery.
After completion of study therapy, patients are followed at 1 month, at 6 months, and then
yearly.
A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma
PRIMARY OBJECTIVES:
l. To determine if trastuzumab increases disease-free survival when combined with trimodality
treatment (radiation plus chemotherapy followed by surgery) for patients with human epidermal
growth factor receptor 2 (HER2)-overexpressing esophageal adenocarcinoma.
SECONDARY OBJECTIVES:
I. To evaluate if the addition of trastuzumab to trimodality treatment increases the
pathologic complete response rate and overall survival for patients with HER2-overexpressing
esophageal adenocarcinoma.
II. To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal
adenocarcinoma.
III. To determine molecular correlates of complete pathologic response, disease-free
survival, and overall survival for patients with HER2-overexpressing esophageal
adenocarcinoma treated with neoadjuvant and maintenance trastuzumab.
IV. To evaluate predictors of cardiotoxicity in patients with esophageal cancer treated with
trastuzumab and chemoradiation.
V. To evaluate adverse events associated with the addition of trastuzumab to trimodality
treatment for patients with non-metastatic esophageal adenocarcinoma.
PATIENT-REPORTED QUALITY OF LIFE OBJECTIVES:
I. To determine if the addition of trastuzumab to trimodality treatment improves the
patient-reported Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E)
Esophageal Cancer Subscale (ECS) score.
II. To determine if an improvement in the FACT-E ECS score at 6-8 weeks post completion of
neoadjuvant chemoradiation correlates with pathologic complete response.
III. To determine if pathologic complete response correlates with the FACT-E ECS score at 1
year and/or 2 years from the start of chemoradiation.
IV. To determine if the addition of trastuzumab to trimodality treatment improves the Swallow
Index and Eating Index Subscale scores of the FACT-E.
V. To determine if the addition of trastuzumab to paclitaxel, carboplatin, and radiation
impacts quality-adjusted survival.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also
receive trastuzumab intravenously (IV) over 30-90 minutes on days 1, 8, 15, 22, 29, 36, and
57 and paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15,
22, 29, and 36. Beginning 21-56 days after surgery, patients receive trastuzumab IV over
30-90 minutes. Treatment repeats every 21 days for 13 courses in the absence of disease
progression or unacceptable toxicity.
ARM II: Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Patients also
receive paclitaxel IV over 60 minutes and carboplatin IV over 30-60 minutes on days 1, 8, 15,
22, 29, and 36.
Within 5-8 weeks after completion of radiotherapy, all patients undergo surgery.
After completion of study therapy, patients are followed up every 4 months for 2 years and
then yearly thereafter.
Phase III Trial of Radiotherapy Plus Cetuximab Versus Chemoradiotherapy in HPV-Associated Oropharynx Cancer
OBJECTIVES:
Primary
- To determine whether substitution of cisplatin with cetuximab will result in comparable
5-year overall survival.
Secondary
- To monitor and compare progression-free survival for "safety".
- To compare patterns of failure (locoregional vs distant).
- To compare acute toxicity profiles (and overall toxicity burden).
- To compare overall quality of life (QOL) short-term (< 6 months) and long-term (1 year).
- To compare QOL Swallowing Domains short-term and long-term.
- To compare clinician-reported versus patient-reported CTCAE toxicity events.
- To explore differences in the cost effectiveness of cetuximab as compared to cisplatin.
- To explore differences in work status and time to return to work.
- To compare patient-reported changes in hearing.
- To compare CTCAE v. 4 late toxicity at 1, 2, and 5 years.
- To evaluate the effect of tobacco exposure (and other exposures) as measured by
standardized computer-assisted self interview (CASI) on overall survival and
progression-free survival.
- To pilot CASI collection of patient reported outcomes in a cooperative group setting.
- To determine whether specific molecular profiles are associated with overall or
progression-free survival.
- To investigate associations between changes in serum biomarkers or human papilloma virus
(HPV)-specific cellular immune responses measured at baseline and three months with
overall or progression-free survival.
OUTLINE: This is a multicenter study. Patients are stratified according to T stage (T1-2 vs T
3-4), N stage (N0-2a vs N2b-3), Zubrod performance status (0 vs 1), and smoking history (≤ 10
pack-years vs > 10 pack-years). Patients are randomized to 1 of 2 treatment arms.
Patients may complete quality-of-life questionnaires and risk factors for head and neck
cancer surveys at baseline, periodically during study, and at follow-up for 1 year.
After completion of study therapy, patients are followed up at 1-3 months, every 3 months for
2 years, every 6 months for 3 years, and then annually thereafter.
Phase II Double-Blinded Placebo-Controlled Study of Bevacizumab With or Without AMG 386 in Patients With Recurrent Glioblastoma or Gliosarcoma
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of AMG 386 (trebananib) 15 mg/kg weekly in
combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1). (closed to accrual 10/2/12)
II. To assess the efficacy of AMG 386 in combination with bevacizumab 10 mg/kg every 2 weeks
compared to bevacizumab monotherapy in bevacizumab-naïve patients, as measured by 6-month
progression-free survival (PFS6) (Cohort 2).
SECONDARY OBJECTIVES:
I. To further assess the toxicity profile (Cohorts 1 and 2). II. To assess feasibility of
AMG 386 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1
[closed to accrual 10/2/12]), as measured by the percentage of patients requiring dose
reduction/interruption or discontinuation in the first 2 and subsequent cycles.
III. To determine the radiographic response rate (RR), median progression-free survival
(PFS), and overall survival (OS) in bevacizumab-naïve patients (Cohort 2).
IV. To assess the efficacy of AMG 386 15 mg/kg weekly in combination with bevacizumab 10
mg/kg every 2 weeks in patients who have progressed while on bevacizumab, as measured by
overall survival (OS) (cross-over from placebo arm of Cohort 2).
V. To correlate outcome to treatment with tumor genotype, expression profile, and
circulating angiogenesis biomarkers in tumor specimens (Cohort 2).
VI. To determine the RR, PFS6, and PFS in patients who have progressed while on bevacizumab
therapy and receive AMG 386 in combination with bevacizumab (cross-over from placebo arm of
Cohort 2).
VII. To determine the serum pharmacokinetics of AMG 386 in patients receiving bevacizumab
(Cohort 1 and cross-over from placebo arm of Cohort 2).
OUTLINE: This is a safety study (cohort 1 [closed to accrual 10/2/12]) followed by a
randomized study (cohort 2).
Cohort 1: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and
15 and trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28
days in the absence of disease progression or unacceptable toxicity. (closed to accrual
10/2/12)
Cohort 2: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive bevacizumab and trebananib as in Cohort 1.
ARM II: Patients receive bevacizumab as in Arm I and placebo IV over 30-60 minutes on days
1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity. Patients with disease progression may cross over to Arm I.
After completion of study treatment, patients are followed up at 30 days, every 2 months for
1 year, every 6 months for 1 year, and then annually thereafter.
Phase III Trial of Dose Escalated Radiation Therapy and Standard Androgen Deprivation Therapy (ADT) With a GNRH Agonist vs. Dose Escalated Radiation Therapy and Enhanced ADT With a GNRH Agonist and TAK-700 For Men With High Risk Prostate Cancer
OBJECTIVES:
Primary
- To evaluate the difference in overall survival of patients with clinically localized
prostate cancer with unfavorable prognostic features between a) standard treatment
(androgen-deprivation therapy [ADT] + radiotherapy) and b) standard treatment with the
addition of 24 months of steroid 17alpha-monooxygenase TAK-700 (TAK-700).
Secondary
- To characterize differences between the treatment groups with respect to incidence of
unexpected grade ≥ 3 adverse events and/or clinically significant decrement in
patient-reported quality of life (QOL) among subjects treated with TAK-700.
- To compare rates and cumulative incidence of biochemical control (freedom from PSA
failure), local/regional progression, and distant metastases.
- To compare rate and cumulative incidence of clinical failure, defined as
prostate-specific antigen (PSA) > 25 ng/mL, documented local disease progression,
regional or distant metastasis, or initiation of ADT.
- To compare prostate cancer-specific survival and other-cause mortality.
- To compare the change in severity of fatigue as measured by the Patient-Reported Outcome
Measurement Information System (PROMIS) fatigue short form.
- To compare changes in patient-reported QOL as measured by Expanded Prostate Cancer Index
Composite (EPIC).
- To assess quality-adjusted survival using the EQ-5D.
- To compare nadir and average serum testosterone at 12 and 24 months during treatment.
- To compare changes in hemoglobin A1C, fasting glucose, and fasting insulin during 24
months of systemic treatment and during the first three years of follow-up.
- To compare changes in fasting lipid levels during 24 months of treatment and during the
first three years of follow-up.
- To compare changes in body mass index (BMI) during 24 months of treatment and during the
first three years of follow-up.
- To compare the incidence of adverse events ascertained via CTCAE version 4.
- To compare the rate of recovery of testosterone to > 230 ng/dL (accepted threshold for
supplementation) after 12 and 24 months of follow-up.
- To compare the median time to recovery of testosterone to > 230 ng/dL during the first
five years of follow-up.
- To assess cumulative incidence of relevant clinical survivorship endpoints including new
diagnosis of type 2 diabetes, coronary artery disease, myocardial infarction, stroke,
pulmonary embolism, deep vein thrombosis, or osteoporotic fracture.
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to risk
group (see Disease Characteristics) and type of radiation therapy (RT) boost
(intensity-modulated RT (IMRT) vs brachytherapy). Patients are randomized to 1 of 2 treatment
arms.
After completion of study therapy, patients are followed every 3 months for 2 years, every 6
months for 1 year, and then annually thereafter.
A Randomized Phase III Study of Standard vs. IMRT Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer (TIME-C)
OBJECTIVES:
Primary
- To determine if pelvic intensity-modulated radiation therapy (IMRT) reduces acute
gastrointestinal toxicity in the 5th week (after 23-25 fractions) of pelvic radiation as
measured with the expanded prostate cancer index composite (EPIC) instrument.
Secondary
- To determine if grade 2+ gastrointestinal toxicity (Common Terminology Criteria for
Adverse Events version 4.0 [CTCAE v. 4.0]) is reduced with IMRT compared to conventional
whole-pelvis radiation therapy (WPRT).
- To determine if grade 2+ hematologic toxicity (CTCAE v. 4.0) is reduced with IMRT
compared to conventional WPRT.
- To determine if urinary toxicity is reduced with IMRT using the EPIC urinary domain.
- To validate EPIC bowel and urinary domains in women undergoing either IMRT pelvic
radiation treatment or four-field pelvic radiation treatment for endometrial or cervical
cancer.
- To assess the impact of pelvic IMRT on quality of life using the Functional Assessment
of Cancer Therapy-General (FACT-G) with cervix subscale.
- To determine if there is any difference in local-regional control, disease-free
survival, and overall survival between patients treated with IMRT as compared to
conventional WPRT.
- To perform a health-utilities analysis to measure the financial impact of pelvic IMRT
via the EQ-5D instrument.
- To identify molecular predictors of radiation toxicity and novel circulating cancer
biomarkers.
OUTLINE: This is a multicenter study. Patients are stratified according to type of cancer
(endometrial vs cervical), chemotherapy (none vs 5 courses of weekly cisplatin at 40 mg/m²),
and radiation dose (45 Gy vs 50.4 Gy). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo standard (3-dimensional) radiation therapy 5 days a week for up
to 5-6 weeks.
- Arm II: Patients undergo intensity-modulated radiation therapy (IMRT) 5 days a week for
up to 5-6 weeks.
Some patients receive cisplatin IV over 1 hour on day 1. Treatment continues weekly for 5
weeks, concurrently with radiation therapy, in the absence of unacceptable toxicity or
disease progression.
Tissue and blood samples may be collected for biomarker and correlative analysis.
Quality of life may be assessed by questionnaires (including the Expanded Prostate Cancer
Index Composite [EPIC], the Functional Assessment of Cancer Therapy-General [FACT-G, Version
4], the EQ-5D, and the Common Toxicity Criteria Adverse Events - Patient-Reported Outcome
[PRO-CTCAE]) instruments at baseline and periodically during and after study therapy.
After completion of study therapy, patients are followed every 6 months for the first 2 years
and then annually for 5 years.
Intergroup Randomized Phase 2 Four Arm Study In Patients ≥ 60 With Previously Untreated Mantle Cell Lymphoma Of Therapy With: Arm A = Rituximab+ Bendamustine Followed By Rituximab Consolidation (RB → R); Arm B = Rituximab + Bendamustine + Bortezomib Followed By Rituximab Consolidation (RBV→ R), Arm C = Rituximab + Bendamustine Followed By Lenalidomide + Rituximab Consolidation (RB → LR) or Arm D = Rituximab + Bendamustine + Bortezomib Followed By Lenalidomide + Rituximab Consolidation (RBV → LR)
OBJECTIVES:
Primary
- To determine whether the addition of bortezomib (RBV) to an induction regimen of
rituximab-bendamustine hydrochloride (RB) improves progression-free survival (PFS)
compared to RB alone in patients ≥ 60 years of age with previously untreated mantle cell
lymphoma.
- To determine whether the addition of lenalidomide to a consolidation regimen of
rituximab following an induction regimen of RB or RBV improves PFS compared to
consolidation rituximab alone in this patient population.
Secondary
- To determine whether the addition of bortezomib to induction therapy improves the
positron emission tomography (PET)-documented complete response (CR) rate compared to RB
alone.
- To determine the objective response rate (ORR) for RB and RBV.
- Among patients who do not have PET-documented CR at the end of induction, to determine
whether the addition of lenalidomide to consolidation therapy improves CR and ORR
compared with rituximab alone.
- To determine overall survival (OS) in the treatment arms.
- To determine safety, with attention to the addition of bortezomib in the induction
regimen and lenalidomide-rituximab (LR) as consolidation therapy.
- To collect paraffin-embedded tissue for creation of tissue microarray.
- To collect and bank serum and blood mononuclear cells for future studies.
- To collect formalin-fixed paraffin-embedded (FFPE) tissue to analyze potential
prognostic factors (Ki-67 proliferation index by immunohistochemistry and correlation
with proposed 5-gene set of proliferation markers analyzed by RNA PCR; SOX 11 expression
by immunohistochemistry; and Micro-RNA levels by microarray).
- Using patient-reported outcomes data, to determine the extent and severity of neuropathy
associated with the addition of bortezomib to induction treatment.
- Using patient-reported outcomes data, to determine the extent and severity of fatigue
associated with the addition of lenalidomide to consolidation treatment.
- To evaluate the effects of the addition of bortezomib and lenalidomide on
patient-reported health-related quality of life.
- To evaluate the effects of bortezomib-related neuropathy on patient-reported
health-related quality of life.
- To evaluate the response of lymphoma-specific symptoms to treatment.
- Using longitudinal patient-reported outcomes data, to describe the trajectory of
lymphoma symptoms, neuropathy, fatigue, and overall health-related quality of life prior
to, during, and following treatment among older adults with MCL.
Tertiary
- To assess the proportion of patients up and down staging when fludeoxyglucose F 18-
(FDG) PET/CT is added to standard Ann Arbor staging.
- To assess the ability of pre-treatment FDG-PET/CT (SUVmax) to predict response rate and
PFS.
- Among patients with interim (post-cycle 3) FDG-PET/CT imaging, to assess the correlation
of interim FDG-PET/CT imaging with response rate and PFS both during induction and
consolidation therapy.
- To assess standard FDG-PET/CT metrics including SUVmax, tumor metabolic burden, total
tumor burden, and association with pathology features (blastoid variant vs other, and
Ki67) in the setting of MCL.
- To assess differences in overall and CR rates when using Deauville vs International
Harmonization Project FDG-PET/CT interpretation criteria.
- To determine whether there is a correlation between FDG-PET/CT response and residual
disease assessment by molecular and/or flow cytometric techniques.
- To determine whether the number of malignant cells in circulation predict the number of
cells in marrow.
- To determine whether the number of malignant cells in circulation/in marrow at the end
of induction correlate with CR and 2-year PFS.
- To determine whether there is a higher rate of minimal residual disease (MRD) negativity
among patients randomized to RBV as compared with RB, and among patients treated with LR
maintenance compared with rituximab.
- To compare the two methods of MRD detection - molecular techniques and flow cytometry -
as prognostic markers for outcome.
OUTLINE: This is a multicenter study. Patients are stratified according to mantle cell
lymphoma International Prognostic Index risk score (low vs intermediate vs high). Patients
are randomized to 1 of 4 treatment arms.
- Arm A: Patients receive induction therapy comprising rituximab IV on day 1 and
bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4
weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm E: Patients receive consolidation therapy comprising rituximab IV on day 1.
Courses repeat every 8 weeks for 2 years in the absence of disease progression or
unacceptable toxicity.
- Arm B: Patients receive induction therapy comprising bortezomib IV or subcutaneously
(SC) on days 1, 4, 8, and 11 and rituximab and bendamustine hydrochloride as patients in
arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease
progression or unacceptable toxicity.
- Arm F: Patients receive consolidation therapy comprising rituximab IV on day 1.
Courses repeat every 8 weeks for 2 years in the absence of disease progression or
unacceptable toxicity.
- Arm C: Patients receive induction therapy comprising rituximab and bendamustine
hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the
absence of disease progression or unacceptable toxicity.
- Arm G: Patients receive consolidation therapy comprising lenalidomide orally (PO)
daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the
absence of disease progression or unacceptable toxicity.
- Arm D: Patients receive bortezomib, rituximab, and bendamustine hydrochloride as
patients in arm B. Treatment repeats every 4 weeks for 6 courses in the absence of
disease progression or unacceptable toxicity.
- Arm H: Patients receive consolidation therapy comprising lenalidomide PO daily on
days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence
of disease progression or unacceptable toxicity.
Patients may undergo blood and bone marrow sample collection at baseline and during treatment
for correlative studies.
Patients complete the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym), the
FACT/GOG-Neurotoxicity scale (FACT/GOG-Ntx), FACT-Fatigue, and FACT-General questionnaires at
baseline and periodically during study and follow up.
After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 3 years, and then annually for 10 years.
Phase III Randomized, Placebo-Controlled Clinical Trial Evaluating the Use of Adjuvant Endocrine Therapy +/- One Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive and HER2/Neu Negative Breast Cancer
OBJECTIVES:
Primary
- To compare whether the addition of one year of everolimus (10 mg daily) to standard
adjuvant endocrine therapy improves invasive disease-free survival (IDFS) in patients
with high-risk, hormone-receptor (HR)-positive, and human epidermal growth factor
receptor (HER)2-negative breast cancer.
Secondary
- To compare whether the addition of one year of everolimus to standard adjuvant endocrine
therapy improves overall survival (OS) and distant recurrence-free survival (DRFS) in
this patient population.
- To evaluate the safety, toxicities, and tolerability of one year of everolimus in
combination with standard adjuvant endocrine therapy and to compare it with standard
adjuvant endocrine therapy plus placebo in this patient population.
- To determine whether the benefit of one year of everolimus use in addition to standard
adjuvant endocrine therapy varies by recurrence score (RS), nodal status, or other
commonly used prognostic factors.
- To evaluate adherence to 1-year treatment of everolimus in comparison to placebo in
addition to standard adjuvant endocrine therapy in this patient population.
- To collect specimens in order to evaluate biomarkers of therapeutic efficacy.
(exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to risk level
(node-negative and recurrence score [RS] > 25 in the primary tumor, and a tumor measuring ≥ 2
cm in greatest diameter treated with adjuvant therapy vs 1-3 positive lymph nodes and RS > 25
treated with adjuvant therapy vs ≥ 4 positive lymph nodes [any RS value] treated with
adjuvant therapy vs ≥ 4 positive lymph nodes [any RS value] prior to or after neoadjuvant
chemotherapy). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive an approved endocrine therapy comprising tamoxifen citrate*,
goserelin acetate** or leuprolide acetate**, or aromatase inhibitor (anastrozole,
letrozole, or exemestane) for 2-5 years. Patients also receive a placebo orally (PO)
daily for 1 year in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive an approved endocrine therapy regimen as in arm I. Patients
also receive everolimus PO daily for 1 year in the absence of disease progression or
unacceptable toxicity.
NOTE: *Men receive tamoxifen citrate PO for 5 years.
NOTE: **Goserelin acetate or leuprolide acetate is given if patient is or becomes
postmenopausal.
Blood and tissue samples are collected for biomarker studies.
After completion of study treatment, patients are followed up every 6 months for 2 years and
then yearly thereafter for 10 years.
Randomized, Double-Blind Phase III Study of Pazopanib vs. Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease Following Metastatectomy
PRIMARY OBJECTIVES:
I. To evaluate disease-free survival with pazopanib (pazopanib hydrochloride) as compared to
placebo, defined as the time from randomization to the development of recurrent disease,
second primary cancer (other than localized breast, localized prostate, or non-melanoma skin
cancer) or death from any cause for patients with metastatic renal cell carcinoma (RCC) with
no evidence of disease following metastasectomy.
SECONDARY OBJECTIVES:
I. To describe the overall survival of patients with advanced RCC randomly assigned to
receive placebo or pazopanib for one year following metastasectomy to no evidence of disease
(NED).
II. To describe treatment and (at recurrence) disease-related adverse events in the two
treatment arms.
III. To analyze quality-adjusted time without symptoms of disease or treatment (Q-TWiST) for
subjects in the two treatment arms.
IV. To characterize changes in patient-reported fatigue and (at recurrence) kidney
cancer-related symptoms during and following treatment with pazopanib compared to placebo.
V. To explore the association between plasma trough levels of pazopanib and disease-free and
overall survival.
VI. To prospectively bank preserved tissue from primary tumors and associated metastatic
sites in patients with RCC.
OUTLINE: Patients are randomized to 1of 2 treatment arms.
ARM I: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28.
Treatment repeats every 28 days for up to 13 courses in the absence of disease progression
or unacceptable toxicity.
ARM II: Patients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up
to 13 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for the first
two years, every 6 months for the next 3 years, and then annually up to 10 years.
A Randomized Double-Blinded Phase III Study Comparing Gemcitabine, Cisplatin, and Bevacizumab to Gemcitabine, Cisplatin, and Placebo in Patients With Advanced Transitional Cell Carcinoma
PRIMARY OBJECTIVES:
I. To determine if patients with advanced transitional cell carcinoma treated with
bevacizumab, gemcitabine (gemcitabine hydrochloride) and cisplatin will have increased
overall survival when compared to patients treated with gemcitabine, cisplatin, and placebo.
SECONDARY OBJECTIVES:
I. To compare the progression-free survival of these two regimens in patients with advanced
transitional cell carcinoma.
II. To compare the proportion of patients who experience an objective response on each
regimen.
III. To compare the grade 3 and greater toxicities in patients treated on the two regimens.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days
1 and 8, cisplatin IV over 1 hour, and placebo IV over 30-90 minutes on day 1. Treatment
repeats every 21 days for 6 courses in the absence of disease progression or unacceptable
toxicity. Patients then receive placebo IV over 30-90 minutes every 21 days in the absence
of disease progression or unacceptable toxicity.
ARM II: Patients receive gemcitabine hydrochloride and cisplatin as in arm I. Patients also
receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6
courses in the absence of disease progression or unacceptable toxicity. Patients then
receive bevacizumab IV over 30-90 minutes every 21 days in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for up to 7
years.
[18F] Fluoroestradiol (FES) PET as a Predictive Measure for Endocrine Therapy in Patients With Newly Diagnosed Metastatic Breast Cancer
PRIMARY OBJECTIVES:
I. To determine the negative predictive value (NPV) of [18F]fluoroestradiol (FES) uptake for
response (clinical benefit) at 6 months in patients with estrogen-receptor positive (ER+)
metastatic breast cancer treated with first-line endocrine therapy.
SECONDARY OBJECTIVES:
I. To determine the test-retest reproducibility of quantitative assessment of tumor FES
uptake by standardized uptake values (SUVs).
II. To evaluate the accuracy of FES-PET/CT for predicting response in patients treated with
first line endocrine therapy for metastatic breast cancer.
III. To evaluate the accuracy of FES-PET/CT for predicting progression-free survival (PFS) in
patients treated with first line endocrine therapy for metastatic breast cancer.
IV. To examine the role of FES-PET/CT in predicting progressive disease (PD) or clinical
benefit (CB), in concert with semi-quantitative interpretation of ER, progesterone receptor
(PgR), and marker of proliferation Ki-67 (Ki-67).
V. To evaluate the relationships among FES uptake, as measured by maximum SUV (SUVmax) and
semi-quantitative ER from immunohistochemistry (IHC).
VI. To evaluate FES SUVmax < 1.5 as the optimal cutpoint for predicting progression-free
survival (PFS) to first line endocrine therapy for metastatic breast cancer.
VII. To determine the percent of eligible patients for whom biopsy is not feasible, i.e.,
determine the clinical utility of indirect assay of ER expression by FES-PET/CT.
VIII. To evaluate the heterogeneity of tumor FES uptake in individual patients defined as
variability in lesion's FES uptake.
OUTLINE:
Between 0 to 30 days before start of endocrine therapy, patients receive F-18 16
alpha-fluoroestradiol intravenously (IV) over 2 minutes and undergo PET/CT. Patients may
undergo a second FES-PET/CT study at least 24 hours after the first study and no later than
10 days after the initial study.
After completion of study, patients are followed up for 6 months and then periodically for up
to 2 years.
Effect of Preoperative Breast MRI on Surgical Outcomes, Costs and Quality of Life of Women With Breast Cancer
This is a randomized trial of preoperative breast MRI in patients deemed eligible for breast
conserving surgery by conventional clinical criteria will provide important information
about the clinical and biologic relevance of occult disease identified by MRI alone.
Patients will be assigned to standard pre-operative breast cancer disease assessment without
the addition of MRI prior to breast conserving surgery or standard pre-operative breast
cancer disease assessment with the use of MRI prior to breast conserving surgery.
The primary objective is to compare the rates of local-regional recurrence (LRR) following
attempted breast conserving therapy in a cohort of women with triple negative or HER-2
amplified breast cancer randomized to preoperative staging with mammography (control arm) or
mammography plus breast MRI (MRI arm).
Secondary objectives are:
- To compare the re-operation rates following attempted breast conserving therapy between
women assessed preoperatively with breast MRI to those assessed without the use of
breast MRI
- To compare local recurrence rates between women who undergo BCT on the control arm to
women who undergo BCT on the MRI arm
- To compare the conversion rate to mastectomy secondary to persistent positive margins
or poor cosmesis within the first 6 months of attempting BCT (prior to the
administration of RT) between women assessed preoperatively with breast MRI to those
assessed without the use of breast MRI
- To compare the contralateral breast cancer rates in women randomized to preoperative
breast MRI to those not receiving pre-operative breast MRI
- To compare the disease-free survival rates between women assessed preoperatively with
breast MRI to those assessed without the use of breast MRI
- To compare breast cancer specific and overall survival outcomes of women assessed
preoperatively with breast MRI to those assessed without the use of breast MRI
- To estimate the rate of MRI-guided localization assisted surgery
- To estimate the rate of multi-centric disease in the index breast for women in the MRI
arm
- To evaluate the accuracy of index lesion characteristics and other factors in
predicting multi-centricity in the cohort randomized to breast MRI
- To assess the positive predictive values (PPV) of MRI in detecting ipsilateral
multi-centric disease and contralateral disease in women with breast cancer undergoing
preoperative breast MRI
- To estimate the false positive rate for detection of multiple foci of breast cancer by
MRI
All registered patients will be monitored for relapse and survival for 5 years from the date
of surgery. Patients will be followed a minimum of every 4 months for the first 2 years from
diagnosis and a minimum of every 6 months during years 3-5. Patients will be monitored for
local, regional, distant relapse and vital status.
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