Randomized Phase III Clinical Trial of Adjuvant Radiation Versus Chemoradiation in Intermediate Risk, Stage I/IIA Cervical Cancer Treated With Initial Radical Hysterectomy and Pelvic Lymphadenectomy (NCT #01101451)
PRIMARY OBJECTIVE:
I. To determine if post-operative adjuvant chemo-radiation therapy (CRT) can significantly
improve recurrence-free survival (RFS) when compared to radiation therapy (RT) alone in stage
I-IIA cervical cancer patients with intermediate-risk factors after treatment with radical
hysterectomy.
SECONDARY OBJECTIVES:
I. To determine whether post-operative adjuvant CRT can improve overall survival (OS) when
compared to RT alone in stage I-IIA cervical cancer patients with intermediate risk factors
after treatment with radical hysterectomy.
II. To assess differences (across treatment arms) in incidence and severity of therapy
attributed adverse events utilizing the active version of Common Terminology Criteria for
Adverse Events (CTCAE).
III. To provide assessment of patient risk version (vs) benefit (positive study only).
QUALITY OF LIFE OBJECTIVE:
I. To determine whether post-operative adjuvant CRT improves the health-related
quality-of-life (QOL) (compared to RT alone) as measured by Functional Assessment of Cancer
Therapy-Cervix (FACT-Cx) Trial Outcome Index (TOI) and produce favorable toxicity profiles
(with particular focus on treatment related genitourinary, gastrointestinal, neurological,
pain and sexual adverse events).
TRANSLATIONAL RESEARCH OBJECTIVES:
I. To bank archival tumor tissue for research studies, including studies that evaluate the
association between biomarkers, RFS, OS, and clinical-surgical-pathologic characteristics in
patients randomized to post-operative adjuvant CRT compared to RT alone.
II. To bank deoxyribonucleic acid (DNA) from whole blood for research studies, including
studies that evaluate associations between single nucleotide polymorphisms (SNPs), and
measures of clinical outcome, including RFS, OS, and adverse events in patients randomized to
post-operative adjuvant CRT compared to RT alone.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated
radiation therapy (IMRT) 5 days a week for 5.5 weeks.
ARM II: Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in
Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of
disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months for 2 years, every
6 months for 3 years, and then annually 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.
Randomized Phase III Study of Sorafenib Versus Stereotactic Body Radiation Therapy Followed by Sorafenib in Hepatocellular Carcinoma
PRIMARY OBJECTIVES:
I. To determine if stereotactic body radiation therapy (SBRT) improves overall survival in
hepatocellular carcinoma (HCC) patients treated with sorafenib (sorafenib tosylate).
SECONDARY OBJECTIVES:
I. To determine the difference in time to progression (TTP) and progression-free survival
(PFS) in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.
II. To measure differences in toxicity in HCC patients treated with sorafenib versus SBRT
followed by sorafenib.
III. To measure vascular thrombosis response post sorafenib versus SBRT followed by
sorafenib.
IV. To measure differences in health related quality of life (QOL) and quality-adjusted
survival in HCC patients treated with sorafenib compared to SBRT followed by sorafenib.
V. Collection of biospecimens for future correlative studies to investigate differences in
potential biomarkers in patients treated with sorafenib versus SBRT followed by sorafenib.
Early Diagnosis of Pulmonary Nodules Using A Plasma Proteomic Classifier, Protocol Number 1001-12
Patients must present with previously non-diagnosed lung nodules as found on CT. There is no
change to the typical standard of care that any of the investigating physicians and/or
centers provide the patients enrolled in this study. The data from this study will not be
used to diagnose cancer nor be used to influence treatment decisions for the study
participants.
A Phase II Study of Bevacizumab Alone or in Combination With TRC105 for Advanced Renal Cell Cancer
PRIMARY OBJECTIVES:
I. To compare the progression-free survival at 12 and 24 weeks for bevacizumab alone or in
combination with TRC105 (anti-endoglin monoclonal antibody TRC105).
SECONDARY OBJECTIVES:
I. Toxicity and Response Evaluation Criteria in Solid Tumors (RECIST) response rate for the
combination compared to single agent bevacizumab.
TERTIARY OBJECTIVES:
I. To evaluate tumor tissue expression of endoglin (CD105), transforming growth factor, beta
receptor II (TGFBR2), activin A receptor type II-like 1 (ACVRL1) and transforming growth
factor, beta receptor 1 (TGFBR1) kinase from pre- and post-treatment tissue samples in order
to determine whether CD105 and stem cell activation occurs after exposure to anti-vascular
endothelial growth factor (VEGF) therapy as predicted by laboratory models, and whether
exposure to anti-endoglin monoclonal antibody TRC105 affects these changes.
II. To compare the soluble CD105 levels at baseline and after treatment between the group
receiving bevacizumab alone and the group receiving bevacizumab in combination with
anti-endoglin monoclonal antibody TRC105.
III. To compare TGFBR2 levels at baseline and after treatment between the group receiving
bevacizumab alone and the group receiving bevacizumab in combination with anti-endoglin
monoclonal antibody TRC105.
IV. To evaluate whether circulating tumor cells (CTCs) can be detected in this patient
population using parylene membrane filter technology, and whether changes in CTC counts and
CD105 expression on CTCs during therapy correspond to imaging and clinical response.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.
ARM II: Patients receive bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105
IV over 1-4 hours on days 1, 8, 15, and 22.
In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease
progression or unacceptable toxicity.
After completion of study therapy, patients are followed up for 4 weeks.
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.
Rate Control Versus Rhythm Control For Postoperative Atrial Fibrillation
The purpose of the research is to compare two strategies for treating atrial fibrillation or
atrial flutter, both of which are referred to as AF, after cardiac surgery. AF is the most
common complication after cardiac surgery. AF is when the upper chambers of the heart (atria)
experience disorganized electrical activity which causes the heart beat to be irregular. The
two treatment strategies to be used in this study are called rhythm control and rate control.
The rhythm control strategy will attempt to bring the heart beat back to a regular rhythm
using treatments known and approved to control heart rhythm. The rate control strategy will
attempt to bring the heart rate to less than 100 beats per minute at rest using medications
known and recommended to control heart rate. Both strategies are commonly used to treat AF.
All of the medications that will be used in this study are the standard of care for use in
patients experiencing AF. This research seeks to determine whether rhythm control is better
than rate control in patients with AF after cardiac surgery.
A Randomized Phase II/Phase III Study of Adjuvant Concurrent Radiation and Chemotherapy Versus Radiation Alone in Resected High-Risk Malignant Salivary Gland Tumors
OBJECTIVES:
Primary
Phase II
- Determine the feasibility of conducting a cooperative group prospective clinical trial
in patients with resected malignant salivary gland tumors.
- Acquire preliminary efficacy data comparing postoperative radiotherapy alone to
concurrent chemotherapy and radiation using weekly cisplatin.
Phase III
* Compare overall survival rates among patients receiving cisplatin and radiation to those
receiving radiation alone.
Secondary
Phase II/III
- Compare the acute toxicities of these 2 adjuvant treatments.
- Compare late treatment-related adverse events in patients receiving postoperative
radiation to those receiving concurrent chemoradiation.
- Compare progression-free survival rates among patients receiving cisplatin and radiation
to those receiving radiation alone in both the cohort of patients with pathologically
high-risk disease (high-grade adenocarcinoma, high-grade mucoepidermoid carcinoma,
salivary duct carcinoma), and the patient cohort with pathologically intermediate-risk
disease (all other eligible diagnoses).
- Investigate quality of life and patient-reported outcomes in patients enrolled in the
study.
- Identify the histopathology and tumor marker expression from patients enrolled on this
trial and assemble a tissue bank for future correlative studies.
- Establish a NRG Oncology baseline database for salivary gland malignancies to serve as a
resource for future exploration of innovative and/or targeted approaches for this
disease.
OUTLINE: This is a multicenter study. Patients are stratified according to histology
(high-grade mucoepidermoid carcinoma vs salivary duct carcinoma vs high-grade adenocarcinoma)
and nodal status (N0 vs N1-3). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo 3-dimensional conformal radiotherapy (3D-CRT) or
intensity-modulated radiotherapy (IMRT) 5 days a week for 6-6.5 weeks. Patients also
receive cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 during
radiotherapy.
- Arm II: Patients undergo 3D-CRT or IMRT as in Arm I. Tissue and blood samples may be
collected for translational research studies. Patients may complete quality-of-life
assessments periodically.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, and 24 months,
every 6 months for 2 years, and then annually thereafter.
Prospective Observational Study to Evaluate Biomarkers of Aminoglycoside Nephrotoxicity in Patients With Cystic Fibrosis
The goal of this clinical study is to advance the acceptance of new biomarkers designed to
detect drug-induced kidney injury in clinical trials.
The Kidney Safety Project is being conducted at four major medical centers:
- University of Southern California
- University of Minnesota
- MD Anderson Cancer Center
- Dana-Farber Cancer Institute.
Blood and urine samples will be collected from patients undergoing treatment with either
cisplatin or aminoglycosides, which are two different drugs known to cause injuries to the
proximal tubule of the kidney. Aminoglycosides are a common antibiotic drug taken by patients
with cystic fibrosis. Cisplatin is a common chemotherapy drug taken by patients with head and
neck cancer.
The Aminoglycoside Study of the Kidney Safety Project is being conducted at the University of
Southern California and the University of Minnesota and aims to evaluate aminoglycoside
induced acute kidney injury in patients with cystic fibrosis.
The companion study, the Cisplatin Study of the Kidney Safety Project, is being conducted at
the MD Anderson Cancer Center and the Dana-Farber Cancer Institute and aims to evaluate
cisplatin induced acute kidney injury in patients with head and neck cancer.
The data from the Kidney Safety Project, from both the Aminoglycoside Study and the Cisplatin
Study, will be combined for determination of the best biomarkers for predicting drug-induced
acute kidney injury.
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.
A Randomized Phase II/III Study of Azacitidine in Combination With Lenalidomide (NSC-703813) vs. Azacitidine Alone vs. Azacitidine in Combination With Vorinostat (NSC-701852) for Higher-Risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)
PRIMARY OBJECTIVES:
I. To select based on response rate (complete remission, partial remission, or hematologic
improvement) either the combination of lenalidomide and azacitidine or the combination of
vorinostat and azacitidine for further testing against single-agent azacitidine among
patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia
(CMML). (Phase II) II. To compare overall survival between the combination arm selected in
the Phase II portion of the trial to single-agent azacitidine among patients with higher-risk
myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). (Phase III)
SECONDARY OBJECTIVES:
I. To estimate relapse-free survival, overall survival and cytogenetic response rate of
patients treated on each regimen.
II. To estimate the frequency and severity of toxicities of the three regimens in this
patient population.
III. To investigate in a preliminary manner the frequency of subgroups from prestudy
cytogenetic studies and correlate these subgroups with clinical outcomes in this patient
population.
IV. To collect specimens for banking for use in future research studies.
TERTIARY OBJECTIVES:
I. To evaluate the prevalence of a pre-specified list of molecular lesions (48 total
lesions).
II. To assess associations of these lesions with outcomes (response, event-free survival,
relapse-free survival, and overall survival).
III. To develop a deoxyribonucleic acid (DNA) methylation biomarker predictive of response to
DMTi treatment in MDS.
IV. To harness gene expression profiles as clinical biomarkers of primary resistance to DMTi
in MDS.
OUTLINE: Patients are randomized to 1 of 3 treatment arms. In Phase III, patients are
randomized to 1 of 2 treatment arms (the combination arm selected in Phase II or the
single-agent azacitidine arm).
ARM I: Patients receive azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 or
days 1-5 and 8-9, and lenalidomide orally (PO) once daily (QD) on days 1-21.
ARM II: Patients receive azacitidine as in Arm I.
ARM III: Patients receive azacitidine as in Arm I and vorinostat PO twice daily (BID) on days
3-9.
In all arms, treatment repeats every 28 days for up to 5 years in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 5
years.
A Phase III Clinical Trial Comparing Trastuzumab Given Concurrently With Radiation Therapy and Radiation Therapy Alone for Women With HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy
PRIMARY OBJECTIVES:
I. To determine the value of trastuzumab given during radiation therapy (RT) compared to RT
alone in preventing subsequent occurrence of ipsilateral breast cancer recurrence,
ipsilateral skin cancer recurrence, or ipsilateral ductal carcinoma in situ (IIBCR-SCR-DCIS)
in women with human epidermal growth factor receptor 2 (HER2)-positive DCIS resected by
lumpectomy.
SECONDARY OBJECTIVES:
I. Determine the value of trastuzumab given during RT compared to RT alone in prolonging
invasive or DCIS disease-free survival (IDFS)-DCIS.
II. Determine the value of trastuzumab given during RT compared to RT alone in increasing
invasive or DCIS recurrence-free interval.
III. Determine the value of trastuzumab given during RT compared to RT alone in improving
regional or distant recurrence.
IV. Determine the value of trastuzumab given during RT compared to RT alone in improving the
incidence of contralateral invasive or DCIS breast cancer.
V. Determine the value of trastuzumab given during RT compared to RT alone in improving
survival.
VI. To explore the effect of trastuzumab on ovarian function.
TERTIARY OBJECTIVES:
I. To determine if the benefit of trastuzumab added to RT will be significantly higher in
v-myc avian myelocytomatosis viral oncogene homolog (cMYC)-amplified tumors than in the cMYC
non-amplified subset.
II. To determine if the benefit of trastuzumab added to RT will be less in tumors with
mutations in the phosphatidylinositol 3 (PI3) kinase gene than in tumors without PI3 kinase
gene mutations.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo standard whole breast irradiation (WBI) over 5-6 weeks.
ARM II: Patients receive trastuzumab intravenously (IV) over 30-90 minutes once in weeks 1
and 4. Patients also undergo WBI as in Arm I.
After completion of study treatment, patients are followed up every 6 months for 5 years and
then every 12 months for 5 years.
Global Registry for Endovascular Aortic Treatment (GREAT)
This is a retrospective and prospective observational cohort Registry designed to obtain data
on the use of the GORE® EXCLUDER® AAA Endoprosthesis with C3 Delivery System. Patient and
device performance outcomes will be collected during treatment and throughout all
post-treatment visits, including follow-up extending up to 10 years.
A Randomized Phase I/II Study of Optimal Induction Therapy of Bortezomib, Dexamethasone and Lenalidomide With or Without Elotuzumab (NSC-764479) for Newly Diagnosed High Risk Multiple Myeloma (HRMM)
PRIMARY OBJECTIVES:
I. To determine the appropriate Phase II dose of elotuzumab to use in combination with
lenalidomide, bortezomib, and dexamethasone for patients with multiple myeloma. (Phase I) II.
To assess whether incorporation of the novel agent elotuzumab into the treatment algorithm of
high-risk multiple myeloma (HRMM) will improve progression-free survival (PFS). (Phase II)
III. To estimate the frequency and severity of toxicities of this treatment strategy in this
patient population. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of elotuzumab, followed by a phase II,
randomized study.
PHASE I:
INDUCTION: Patients receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1,
4, 8, and 11; lenalidomide orally (PO) once daily (QD) on days 1-14; and dexamethasone PO or
IV on days 1, 2, 4, 5, 8, 9, 11, and 12 (and on day 15 of courses 1 and 2 only). Patients
also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of
courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease
progression or unacceptable toxicity.
MAINTENANCE: Patients receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on
days 1-21; dexamethasone PO on days 1, 8, and 15; and elotuzumab IV on days 1 and 15.
Treatment repeats every 28 days in the absence of disease progression or unacceptable
toxicity.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM I:
INDUCTION: Patients receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD
on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment
repeats every 21 days for 8 courses in the absence of disease progression or unacceptable
toxicity (patients who received a course of chemotherapy prior to registration will begin
protocol treatment with course 2 and receive a total of 7 courses of protocol therapy).
MAINTENANCE: Patients receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on
days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.
ARM II:
INDUCTION: Patients receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Patients
also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of
courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease
progression or unacceptable toxicity.
MAINTENANCE: Patients receive bortezomib, lenalidomide, and dexamethasone as in Arm I.
Patients also receive elotuzumab IV on days 1 and 15. 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 up to 6
years.
A Randomized Gene Fusion Stratified Phase 2 Trial of Abiraterone With or Without ABT-888 for Patients With Metastatic Castration-Resistant Prostate Cancer
PRIMARY OBJECTIVES:
I. To evaluate the role of v-ets erythroblastosis virus E26 oncogene (ETS) gene fusion as a
predictive biomarker for response to hormone therapy (abiraterone [abiraterone acetate])
alone or hormone therapy plus poly adenosine diphosphate-ribose polymerase 1 (PARP-1)
targeted therapy (ABT-888 [veliparib]) in patients with metastatic castration resistant
prostate cancer.
II. To evaluate whether the addition of PARP-1 targeted therapy is superior to hormone
therapy alone based on ETS gene fusion status.
SECONDARY OBJECTIVES:
I. Rate of prostate-specific antigen (PSA) declines. II. Objective response rate. III.
Progression-free survival. IV. Evaluate the qualitative and quantitative toxicity of
abiraterone acetate with and without ABT-888.
TERTIARY OBJECTIVES:
I. To determine the concordance in fusion status among prostate cancer samples from the
primary site, biopsied metastasis, and circulating tumor cells (CTCs).
II. To assess if ETS fusion status in the CTCs, at baseline, 12 weeks, and disease
progression (or when off study) is associated with response to therapy.
III. To evaluate if the number of CTCs, as well as the expression levels of androgen
receptor, RAD51 recombinase (RAD51), and gamma-H2A histone family, member X (H2aX) foci in
the CTCs at baseline, at 12 weeks, and at disease progression in all patients is associated
with response to therapy.
IV. To determine the role of phosphatase and tensin homolog (PTEN) loss as a predictive
biomarker of response to abiraterone, alone or in combination with ABT-888.
V. To determine the role of PARP1 activity as a predictive biomarker of response to
abiraterone, alone or in combination with ABT-888.
VI. To perform next-generation sequencing for discovery of novel gene fusions in prostate
cancers negative for ETS fusions.
VII. To perform germline single nucleotide polymorphism (SNP) analysis of genes involved in
hormone synthesis, transport, binding, metabolism, and degradation for discovery of novel
SNPs predictive of response to abiraterone, alone or in combination with ABT-888.
VIII. To determine if ETS fusion ribonucleic acid (RNA) levels in blood are predictive of
response to abiraterone, alone or in combination with ABT-888.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive abiraterone acetate orally (PO) once daily (QD) and prednisone PO
twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
ARM II: Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone
acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). 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 2
years.
Powered by
SC CTSI