Phase III Trial of Enzalutamide (NSC# 766085) Versus Enzalutamide, Abiraterone and Prednisone for Castration Resistant Metastatic Prostate Cancer
Patients are randomized to one of two treatment groups: enzalutamide or enzalutamide,
abiraterone and prednisone. Treatment will continue until disease progression or
unacceptable toxicity. Patients are followed for clinical outcomes for a maximum of 5 years
post study treatment. The primary and secondary objectives are described below.
1. Primary Objective:
To compare the overall survival of patients with progressive metastatic
castration-resistant prostate cancer (CRPC) treated with either enzalutamide only or
enzalutamide with abiraterone and prednisone
2. Secondary Objectives:
- To assess the grade 3 or higher toxicity profile and compare safety by treatment
arm.
- To assess and compare post-treatment prostate-specific antigen (PSA) declines by
treatment arm.
- To compare radiographic progression free survival defined by Prostate Cancer
Working Group 2 (PCWG2), and objective response rate, by treatment arm.
- To test for radiographic progression free survival (rPFS) treatment interaction in
predicting overall survival.
- To assess pre- and post-treatment measures of tumor burden and bone activity using
sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT)
and technetium (Tc) methylene diphosphonate (MDP) bone scintigraphy and correlate
these measures with overall survival.
- To develop and validate prognostic and predictive models of overall survival that
include baseline clinical and molecular markers.
A Phase III Trial of 6 Versus 12 Treatments of Adjuvant FOLFOX Plus Celecoxib or Placebo for Patients With Resected Stage III Colon Cancer
OBJECTIVES:
Primary
- To compare disease-free survival of patients with resected stage III colon cancer
treated with adjuvant FOLFOX chemotherapy comprising oxaliplatin, fluorouracil, and
leucovorin calcium with versus without celecoxib.
Secondary
- To contribute to an international prospective pooled analysis comparing disease-free
survival of patients treated with these regimens.
- To compare overall survival at 3 years of patients treated with these regimens.
- To contribute to an international prospective pooled analysis comparing disease-free
survival of patients treated with 6 versus 12 courses of FOLFOX chemotherapy.
- To assess toxicities of celecoxib as maintenance adjuvant therapy in these patients.
- To assess differences in cardiovascular-specific events in patients treated with versus
without celecoxib.
- To evaluate differences in toxicities, particularly cumulative peripheral neuropathy,
in patients treated with 6 versus 12 courses of FOLFOX chemotherapy.
OUTLINE: This is a multicenter study. Patients are stratified according to number of
positive lymph nodes* (1-3 vs 4 or more) and concurrent regular low-dose of aspirin (yes vs
no). Patients are randomized to 1 of 4 treatment arms.
NOTE: *Patients with N1c-only disease (i.e., no positive nodes but N1c disease by AJCC 7)
should be stratified to 1-3 nodes.
- Arm I: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2
hours, and fluorouracil IV continuously over 46-48 hours (FOLFOX) on day 1. Patients
also receive oral celecoxib once daily on days 1-14 beginning on day 1 of course 2 of
FOLFOX. Courses repeat every 14 days for 12 courses in the absence of disease
progression or unacceptable toxicity.
- Arm II: Patients receive FOLFOX as in arm I and oral placebo once daily on days 1-14
beginning on day 1 of course 2. Courses repeat every 14 days for 12 courses in the
absence of disease progression or unacceptable toxicity.
- Arm III: Patients receive FOLFOX and celecoxib as in arm I. Courses repeat every 14
days for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm IV: Patients receive FOLFOX and placebo as in arm II. Courses repeat every 14 days
for 6 courses in the absence of disease progression or unacceptable toxicity.
In all arms, treatment with celecoxib or placebo continues for 3 years in the absence of
disease progression or unacceptable toxicity.
Blood and tissue samples maybe collected for biomarker analysis and pharmacogenomic studies.
After completion of study therapy, patients are followed up every 3 months for 1 year, every
6 months for years 2-3, and then annually for 3 years.
Not recruiting | Colon / Rectal Cancer | Multisite
A Phase III Randomized, Double-Blind Trial of Chemoembolization With or Without Sorafenib in Unresectable Hepatocellular Carcinoma (HCC) in Patients With and Without Vascular Invasion
PRIMARY OBJECTIVE:
I. To compare progression-free survival (PFS) of chemoembolization alone to sorafenib
(sorafenib tosylate) in combination with chemoembolization.
SECONDARY OBJECTIVES:
I. To compare overall survival (OS) of chemoembolization alone to sorafenib in combination
with chemoembolization.
II. To evaluate extra-hepatic versus intra-hepatic patterns of failure. III. To determine
the rates of toxicity related to sorafenib in combination with chemoembolization.
TERTIARY OBJECTIVES:
I. To analyze the pharmacogenetic and pharmacokinetic properties of sorafenib including
angiogenesis, monooxygenases, polymorphisms and multidrug resistance (MDR).
II. Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network
(ACRIN) secondary imaging objective: site vs. central evaluation of PFS.
III. To determine the inter-reader concordance for response characterization at four and
eight months by the European Association for the Study of Liver (EASL) criteria.
IV. To determine the value of objective tumor response at four and eight months by the EASL
criteria to predict PFS (by Response Evaluation Criteria in Solid Tumors [RECIST]) and OS.
V. To evaluate the effects of intra-hepatic vs. extra-hepatic progression on OS.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive sorafenib tosylate orally (PO) twice daily (BID) in the absence of
disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose
of sorafenib tosylate is reached, patients undergo transarterial chemoembolization (TACE)
comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (closed to accrual as of
10/1/2010); conventional chemoembolization comprising doxorubicin hydrochloride only; or
chemoembolization comprising doxorubicin-eluting beads. Treatment with TACE repeats
approximately every 4 weeks for up to 4 courses in the absence of disease progression or
unacceptable toxicity.
ARM II: Patients receive placebo PO BID in the absence of disease progression or
unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached,
patients undergo TACE as in Arm I.
MAINTENANCE THERAPY: After completion of chemoembolization, patients receive sorafenib
tosylate or placebo as in Arm I and II in the absence of disease progression or unacceptable
toxicity.
After completion of study treatment, patients are followed up for 4 years.
A Randomized Phase III Trial of the Value of Early Local Therapy for the Intact Primary Tumor in Patients With Metastatic Breast Cancer
OBJECTIVES:
Primary
- To evaluate whether early local therapy comprising surgery of intact primary disease
compared to local palliative therapy only in patients with stage IV breast cancer,
whose disease does not progress during initial optimal systemic therapy, will result in
prolonged survival.
Secondary
- To compare the time to uncontrolled chest wall disease between patients treated with
these regimens.
- To determine whether there is a difference in health-related quality-of-life (HRQOL)
between patients treated with these regimens.
- To determine whether the absolute value of circulating tumor cells (CTC) burden at 6
months following randomization (time +6) will be lower in the palliative therapy arm
than in early local therapy arm, and whether this value is inversely related to
survival (lower CTC, longer survival).
- To collect tumor and blood specimens for future exploration of the biological
interactions between the primary tumor and metastatic lesions and the effect of primary
tumor resection.
OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor
and treatment plan (ER+ or PR+, HER2-, endocrine therapy alone vs ER+ or PR+, and HER2-,
chemotherapy and/or endocrine therapy vs ER- or PR-, and HER2- vs HER2+), and number of
involved organ systems with distant disease (regional nodes in the axillary,
supraclavicular, and internal mammary locations are not considered distant sites) (1 vs >
1). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive standard palliative therapy, if needed, to address symptoms
such as tumor ulceration, pain, bulky adenopathy causing arm symptoms, and other
similar situations. Therapy may consist of radiotherapy alone, surgery alone, or a
combination of both.
- Arm II: Patients undergo surgery comprising breast-conserving therapy (BCT) or total
mastectomy according to patient and treating physician preference. Surgery is to occur
no later than 10 weeks after completion of 32 weeks of systemic therapy. Free surgical
margins must be achieved with re-excision or mastectomy for patients undergoing BCT.
After completion of BCT, patients undergo radiotherapy once a day, 5 days per week.
Patients who had mastectomy undergo radiotherapy at the discretion of treating
physician.
Patients may undergo blood and tumor tissue sample collection for circulating tumor cells
(CTC) burden and future studies.
Patients complete the Functional Assessment of Cancer Therapy - Breast Trial Outcome Index
(FACT- TOI) and FACT - General (22) and the Breast Cancer Subscale (FACT-B) quality-of-life
questionnaires at baseline and periodically during study.
After completion of study therapy, patients are followed up periodically for 5 years.
A Phase I/II Trial of Vorinostat (SAHA) (NSC-701852) in Combination With Rituximab-CHOP in Patients With Newly Diagnosed Advanced Stage Diffuse Large B-Cell Lymphoma (DLBCL)
PRIMARY OBJECTIVES:
I. To find a safe dose of vorinostat to be used in combination with R-CHOP (rituximab,
cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone)
(vorinostat-R-CHOP). (Phase I) II. To estimate the 2-year progression-free survival (PFS)
rate in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with
vorinostat and R-CHOP therapy (vorinostat-R-CHOP). (Phase II) III. To estimate the response
rate (complete and partial) and 2-year overall survival rate. (Phase II) IV. To evaluate the
toxicity of vorinostat-R-CHOP in patients with newly diagnosed DLBCL. (Phase II) V. To assess
whether pre-treatment acetylation status of histones, expression of major histocompatibility
complex (MHC) class II genes, and/or percentage of cluster of differentiation (CD)8+ tumor
infiltrating lymphocytes correlate with progression-free survival. (Phase II) VI. To explore
whether treatment with vorinostat-R-CHOP increases histone acetylation, alters expression of
MHC class II proteins, or alters percentage of T-cell subsets (CD8+, CD4+, forkhead box P3
[FOXP3]+) or infiltrating macrophages. (Phase II) VII. To explore whether histone acetylation
status of tumor tissues correlates with MHC class II expression of peripheral blood B cells
and lymphocyte subsets. (Phase II) VIII. To explore whether the change in systemic levels of
immune cytokines with vorinostat-R-CHOP correlates with lymphoma symptoms, response,
progression-free or overall survival. (Phase II)
OUTLINE: This is a phase I, dose escalation study of vorinostat followed by a phase II study.
Patients receive vorinostat orally (PO) once daily on days 1-5 or 1-9 (according to dose
level), rituximab intravenously (IV), cyclophosphamide IV over 30-60 minutes, doxorubicin
hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO
once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of
disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 6 months for 2 years, and
then annually for 3 years.
Randomized Phase II Clinical Trial of AZD6244 Hydrogen Sulfate (NSC-748727) and MK-2206 (NSC-749607) vs mFOLFOX in Patients With Metastatic Pancreatic Cancer After Prior Chemotherapy
PRIMARY OBJECTIVES:
I. To assess overall survival in patients with metastatic pancreatic cancer treated with the
combination of AZD6244 hydrogen sulfate (selumetinib) and MK-2206 (Akt inhibitor MK2206)
compared to those treated with mFOLFOX.
SECONDARY OBJECTIVES:
I. To assess the frequency and severity of toxicity associated with the combination of
AZD6244 hydrogen sulfate and MK-2206 compared to those with mFOLFOX in this patient
population.
TERTIARY OBJECTIVES:
I. To assess progression free survival (PFS) in patients with metastatic pancreatic cancer
treated with the combination of AZD6244 hydrogen sulfate and MK-2206 compared to those
treated with mFOLFOX.
II. To assess objective tumor response in the subset of patients with measurable disease
(confirmed and unconfirmed complete and partial response) in patients with metastatic
pancreatic cancer treated with the combination of AZD6244 hydrogen sulfate and MK-2206
compared to those treated with mFOLFOX.
III. To bank tissue and blood for future translational medicine studies.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours on days 1 and 15 and
fluorouracil IV over 46-48 hours on days 1-2 and 15-16 (mFOLFOX).
ARM II: Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, 15, and 22, and
selumetinib PO daily on days 1-28.
In all arms, courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for up to 3
years.
A Randomized Phase III Double Blind Clinical Trial Evaluating the Effect of Immune-Enhancing Nutrition on Radical Cystectomy Outcomes
PRIMARY OBJECTIVE:
I. To compare the impact of consuming perioperative specialized immune-modulating drinks
(SIM, Impact Advanced Recovery, Nestle) to oral nutrition supplement control drinks (ONS,
Oral Nutrition Control, Nestle) on post-operative complications (any versus [vs.] none)
within 30 days after scheduled radical cystectomy (RC).
SECONDARY OBJECTIVES:
I. To assess whether SIM use compared to ONS reduces late-phase post-operative complications
within 90 days after scheduled RC.
II. To assess whether SIM use compared to ONS reduces infections. III. To assess whether SIM
use compared to ONS reduces skeletal muscle wasting. IV. To assess whether SIM use compared
to ONS reduces high grade post-operative complications.
V. To assess whether SIM use compared to ONS reduces readmission rates. VI. To assess whether
SIM use compared to ONS improves quality of life. VII. To assess whether SIM use compared to
ONS improves disease-free survival after surgery and overall survival.
TERTIARY OBJECTIVES:
I. To assess the impact of SIM use on the expansion of myeloid-derived suppressor cells.
II. To assess the impact of SIM use on pro-inflammatory cytokines and neutrophil: lymphocyte
ratios.
III. To assess the impact of SIM use on post-operative arginine deficiency and amino acid
metabolism.
IV. To explore the association of dietary intake variables (nutrition status, calories,
protein, and immune-enhancing factors) and study outcomes.
TRANSLATIONAL MEDICINE OBJECTIVES:
I. To describe the microbiome of the gut in patients undergoing radical cystectomy and
urinary diversion prior to initiation of immunonutrition or a nutrition control.
II. To define the microbiome change in patients undergoing radical cystectomy and urinary
diversion after they have received blinded immunonutrition or control nutritional supplement.
III. To correlate cancer treatments, postoperative complications (specifically infections)
and nutritional status with microbiome composition.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive SIM orally (PO) thrice daily (TID) on days -5 to -1 and 1-5. Patients
undergo standard of care surgery on day 0.
ARM II: Patients receive placebo PO TID on days -5 to -1 and 1-5. Patients undergo standard
of care surgery on day 0.
After completion of study, patients are followed up at 2, 30, and 90 days, and at 6, 9, 12,
18, 24, and 36 months after surgery.
A Phase I/Randomized Phase II Study of Cediranib (NSC#732208) Versus Placebo in Combination With Cisplatin and Pemetrexed in Chemonaive Patients With Malignant Pleural Mesothelioma
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose (MTD) and the recommended phase II dose of
cediranib maleate (cediranib) in combination with cisplatin and pemetrexed disodium
(pemetrexed). (Phase I) II. To assess the safety and toxicity of the regimen. (Phase I) III.
To assess whether cisplatin/pemetrexed plus cediranib as compared to cisplatin/pemetrexed
plus placebo improves progression-free survival in patients with malignant pleural
mesothelioma. (Phase II) IV. To compare overall survival in patients treated with
cisplatin/pemetrexed plus cediranib to those treated with cisplatin/pemetrexed plus placebo.
(Phase II) V. To assess the safety and toxicity profile of the regimen. (Phase II) VI. To
assess response rate (confirmed and unconfirmed, complete and partial responses) and disease
control rate (response or stable disease) in the subset of patients with measurable disease
by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. (Phase II) VII. To assess
response rate and disease control rate using modified RECIST criteria for pleural tumors in
the subset of patients with measurable disease by modified RECIST criteria for pleural
tumors. (Phase II) VIII. To assess the rate of agreement between local and central pathology
review of mesothelioma and its histologic subtypes. (Phase II) IX. To collect specimens for
banking for use in future research studies. (Phase II)
OUTLINE: This is a phase I dose-escalation study of cediranib maleate followed by a phase II
study.
PHASE I (CLOSED): Patients receive pemetrexed disodium intravenously (IV) over 10 minutes and
cisplatin IV over 2 hours on day 1 and cediranib maleate orally (PO) once daily (QD) on days
1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or
unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of
disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours
on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6
courses in the absence of disease progression or unacceptable toxicity. Patients then receive
cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive pemetrexed disodium and cisplatin as in arm I and placebo PO QD on
days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease
progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 2 years and
then at 3 years.
A Phase II Study of MK-2206 (NSC-749607) as Second Line Therapy for Advanced Gastric and Gastroesophageal Junction Cancer
PRIMARY OBJECTIVES:
I. To estimate the overall survival (OS) for patients with advanced gastric and
gastroesophageal junction (GEJ) adenocarcinoma treated with MK-2206 (Akt inhibitor MK2206).
SECONDARY OBJECTIVES:
I. To estimate the progression free survival (PFS) in this patient population. II. To
estimate the response rate (confirmed and unconfirmed complete response [CR] and partial
response [PR] by Response Evaluation Criteria In Solid Tumors [RECIST] 1.1) in this patient
population.
III. To assess the frequency and severity of toxicity associated with this regimen.
OUTLINE (CLOSED TO ACCRUAL 05/01/13):
Patients receive Akt inhibitor MK2206 orally (PO) every other day on days 1-28. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months for 2 years.
A Phase III, Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy +/- Chemotherapy in Patients With 1-3 Positive Nodes, Hormone Receptor-Positive and HER2-Negative Breast Cancer With Recurrence Score (RS) of 25 or Less. RxPONDER: A Clinical Trial Rx for Positive Node, Endocrine Responsive Breast Cancer
PRIMARY OBJECTIVE:
I. To determine the effect of chemotherapy in patients with node positive breast cancer who
do not have high recurrence scores (RS) by Oncotype DX.
SECONDARY OBJECTIVES:
I. To compare overall survival (OS), distant disease-free survival (DDFS) and local
disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS.
II. To compare the toxicity across the treatment arms. III. To perform other molecular assays
or test other signatures that measure prognosis and potential benefit of chemotherapy and
compare them to Oncotype DX.
IV. To determine the impact of management with Oncotype DX on patient-reported anxiety
(co-primary Health-Related Quality of Life [HRQL] outcome) prior to screening, after
disclosure of test results, and during the randomized trial.
V. To determine the impact of Oncotype DX on the initial management cost of node-positive,
hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative
breast cancer.
VI. To compare patient-reported utilities (e.g., quality of life [QOL]) for those randomized
to chemotherapy versus no chemotherapy.
VII. Using modeling and DFS information from the trial, to estimate the cost-effectiveness of
management with Oncotype DX vs usual care.
VIII. To determine the role of other assays as predictors of DFS, DDFS, and LDFI for patients
randomized to chemotherapy versus no chemotherapy.
IX. To determine the impact of treatment with chemotherapy versus no chemotherapy on
patient-reported fatigue and cognitive concerns (secondary HRQL outcomes).
X. To determine the impact of management with Oncotype DX on patient-reported decision
conflict, perceptions regarding Oncotype DX testing, and survivor concerns prior to
screening, after disclosure of test results, and during the randomized trial (secondary HRQL
outcomes).
XI. The presence of circulating tumor cells (CTC+) using two CTC platforms will be assessed
at up to two time points to assess late recurrence in those still at risk for the primary
outcome.
XII. To compare clinically reported menopausal status with status categorized by serum
hormone levels determined from baseline serum in women under age 55 years and to assess
subsequent association with outcomes.
BANKING OBJECTIVE:
I. To bank specimens for future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive a protocol-approved chemotherapy regimen based on the patient and/or
physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy
comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane),
or both for 5-10 years in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate,
an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year,
every 6 months for 4 years, and then yearly for 15 years.
A Phase III Surgical Trial to Evaluate the Benefit of a Standard Versus an Extended Pelvic Lymphadenectomy Performed at Time of Radical Cystectomy for Muscle Invasive Urothelial Cancer
OBJECTIVES:
Primary
- To compare disease-free survival (DFS) of patients with muscle-invasive urothelial
carcinoma of the bladder undergoing radical cystectomy with extended pelvic lymph node
dissection (PLND) or standard pelvic lymphadenectomy.
Secondary
- To compare overall survival (OS) of patients randomized to extended PLND versus those
randomized to standard pelvic lymphadenectomy.
- To evaluate operative time; whether or not nerve sparing was performed, intraoperative,
peri-operative and 90-day morbidity and mortality; length of hospital stay; histology
(pure urothelial versus mixed); lymph node counts and lymph node density; adjuvant
chemotherapy received; and local and retroperitoneal soft tissue recurrence in patients
randomized to extended PLND versus those randomized to standard pelvic lymphadenectomy.
- To collect peripheral blood and two paraffin-embedded blocks of the primary tumor for
translational medicine studies, including circulating tumor cells (CTCs) and markers of
epithelial and mesenchymal transition, and correlate these findings with pathologic T
stage and node metastasis as well as DFS and OS.
OUTLINE: This is a multicenter study. Patients are stratified according to prior neoadjuvant
therapy (yes vs no), clinical stage (T2 vs T3 vs T4a), and Zubrod performance status (0-1 vs
2). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo radical cystectomy and standard pelvic lymphadenectomy.
- Arm II: Patients undergo radical cystectomy and extended pelvic lymphadenectomy.
Blood and tumor specimens may be collected periodically for translational studies.
After completion of study therapy, patients are followed up periodically for 6 years.
Abiraterone Acetate Treatment for Prostate Cancer Patients With a PSA of More Than Four Following Initial Androgen Deprivation Therapy Phase II
OBJECTIVES:
Primary
- To assess the rate of achieving a prostate-specific antigen (PSA) of ≤ 0.2 ng/mL with
abiraterone acetate therapy in men with metastatic prostate cancer with a sub-optimal
response to androgen-deprivation therapy (ADT).
Secondary
- To assess the overall survival and objective progression-free survival of this group of
patients.
- To assess PSA partial response.
- To evaluate the qualitative and quantitative toxicity of abiraterone acetate.
OUTLINE: This is a multicenter study.
Patients receive abiraterone acetate orally daily on days 1-28. Courses repeat every 28 days
in the absence of disease progression or unacceptable toxicity.
Patients receive androgen blockade with GNRH agonist (goserelin acetate or leuprolide
acetate) or a GNRH antagonist (degarelix) per the treating physician and this will be given
continuously until evidence of disease progression. Bilateral surgical orchiectomy is also
acceptable.
After completion of study therapy, patients are followed up every 3 months for 1 year and
then every 6 months for up to 3 years.
Parallel (Randomized) Phase II Evaluation of ARQ 197 and ARQ 197 in Combination With Erlotinib in Papillary Renal Cell Carcinoma
PRIMARY OBJECTIVES:
I. To assess the response rate (confirmed complete and partial response) of patients with
locally advanced or metastatic papillary renal cell carcinoma treated with either ARQ 197
(tivantinib) or ARQ 197 combined with erlotinib (erlotinib hydrochloride).
SECONDARY OBJECTIVES:
I. To assess the progression free survival (PFS) of patients with locally advanced or
metastatic papillary renal cell carcinoma treated with either ARQ 197 or ARQ 197 combined
with erlotinib.
II. To assess the safety and tolerability of ARQ 197 therapy and ARQ 197 combined with
erlotinib.
III. To descriptively assess the role of prior treatment on outcome.
TERTIARY OBJECTIVES:
I. To bank tissue specimens for future use and once funding is obtained to evaluate the
expression of tissue correlative biomarkers such as hepatocyte growth factor receptor (c-MET)
and epidermal growth factor receptor (EGFR), and to perform exploratory correlation with
clinical outcomes.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28.
ARM II: Patients receive tivantinib PO BID and erlotinib hydrochloride PO once daily (QD) on
days 1-28.
In both arms, courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and
then every 6 months for up to 2 years.
S1313, A Phase IB/II Randomized Study of Modified FOLFIRINOX + Pegylated Recombinant Human Hyaluronidase (PEGPH20) Versus Modified FOLFIRINOX Alone in Patients With Good Performance Status Metastatic Pancreatic Adenocarcinoma
PRIMARY OBJECTIVES:
I. To assess the safety of modified leucovorin calcium, fluorouracil, irinotecan
hydrochloride and oxaliplatin (mFOLFIRINOX) in combination with PEGPH20 and select the
optimal dose of PEGPH20 for the phase II portion in patients with metastatic pancreatic
adenocarcinoma. (Phase I) II. To assess the overall survival of patients with metastatic
pancreatic adenocarcinoma treated with mFOLFIRINOX + PEGPH20 compared to those treated with
mFOLFIRINOX alone. (Phase II)
SECONDARY OBJECTIVES:
I. To assess progression free survival (PFS) in patients receiving mFOLFIRINOX with PEGPH20
and patients receiving mFOLFIRINOX alone in this patient population.
II. To assess objective tumor response (confirmed and unconfirmed, complete and partial) in
patients with measurable disease treated with mFOLFIRINOX with PEGPH20 and patients receiving
mFOLFIRINOX alone in this patient population.
III. To determine the frequency, severity, and tolerability of adverse events of mFOLFIRINOX
with PEGPH20.
TERTIARY OBJECTIVES:
I. To explore the correlation of maximum decrease in cancer antigen (CA) 19-9 levels and time
to maximum decrease in CA 19-9 levels with overall survival, progression-free survival and
response.
II. To explore the correlation of plasma hyaluronan (HA) and tumor expression of HA with
overall survival, progression-free survival and response.
OUTLINE: This is a phase I, dose de-escalation study of pegylated recombinant human
hyaluronidase followed by a randomized phase II study.
PHASE I: Patients receive pegylated recombinant human hyaluronidase intravenously (IV) over
10 minutes on day 1*; oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and
irinotecan hydrochloride IV over 1.5 hours on day 2; and fluorouracil IV over 46 hours on
days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable
toxicity.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and
irinotecan hydrochloride IV over 1.5 hours on day 2, and fluorouracil IV over 46 hours on
days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable
toxicity.
ARM II: Patients receive pegylated recombinant human hyaluronidase IV over 10 minutes on day
1* and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and fluorouracil as in Arm
I. Courses repeat every 14 days in the absence of disease progression or unacceptable
toxicity.
*NOTE: Some patients also receive pegylated recombinant human hyaluronidase on day 3 or 4 of
courses 1 and 2.
After completion of study treatment, patients are followed up for 3 years.
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