Recurrent Rectal Cancer Clinical Trial
Official title:
A Phase 2 Study of RO4929097 (NSC 749225) in Combination With FOLFOX Plus Bevacizumab Versus FOLFOX Plus Bevacizumab Alone for the First-Line Treatment of Patients With Metastatic Colorectal Cancer (NCI #8467)
This phase II clinical trial is studying how well giving combination chemotherapy and bevacizumab with or without RO4929097 works in treating patients with metastatic colorectal cancer. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy and bevacizumab is more effective with RO4929097 in treating patients with colorectal cancer.
PRIMARY OBJECTIVES:
I. To estimate the efficacy, as determined by progression-free survival, of FOLFOX6 and
bevacizumab with versus without gamma-secretase inhibitor RO4929097 (RO4929097).
SECONDARY OBJECTIVES:
I. To estimate the clinical benefit of RO4929097 in combination with mFOLFOX6 and
bevacizumab, as measured by objective response rate.
II. To evaluate the safety and tolerability of RO4929097 in combination with mFOLFOX6
chemotherapy and bevacizumab.
III. To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of RO4929097 in
combination with mFOLFOX6 and bevacizumab.
IV. To investigate PD response of RO4929097 in combination with mFOLFOX6 chemotherapy and
bevacizumab, as assessed by direct measurement of gamma-secretase enzyme activity, in tumor
samples.
V. (Exploratory) To investigate the Notch signaling pathway genes targeted by RO4929097 in
combination with mFOLFOX6 chemotherapy and bevacizumab and correlate with clinical outcome.
VI. (Exploratory) To investigate the Ras signaling pathway genes targeted by RO4929097 in
combination with mFOLFOX6 chemotherapy and bevacizumab and correlate with clinical outcome.
VII. (Exploratory) To investigate putative colorectal cancer stem cells targeted by
RO4929097 in combination with mFOLFOX6 chemotherapy and bevacizumab and correlate with
clinical outcome.
OUTLINE: This is a multicenter study. Patients are stratified according to participating
center, prior therapy (adjuvant/neoadjuvant vs none), and number of organs* involved by
metastases (1 vs > 1). Patients are randomized to 1 of 2 treatment arms.
NOTE: *Lesions all in the liver would be considered as 1 organ involved.
ARM I: Patients receive FOLFOX6 regimen comprising oxaliplatin intravenously (IV) over 2
hours, leucovorin calcium IV over 2 hours, fluorouracil IV continuously over 46 hours, and
bevacizumab IV over 30-90 minutes on days 1-2. Patients also receive oral gamma-secretase
inhibitor RO4929097 on days 1-3 and 8-10.
Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity
(RO4929097 is given for up to 12 courses).
ARM II: Patients receive FOLFOX6 regimen and bevacizumab as in arm I.
Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Patients may undergo blood sample collection at baseline and periodically during study for
pharmacokinetic, pharmacodynamic, and correlative studies.
After completion of study therapy, patients are followed up for 12 months.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT01987726 -
Comprehensive Gene Sequencing in Guiding Treatment Recommendations Patients With Metastatic or Recurrent Solid Tumors
|
||
Active, not recruiting |
NCT00826540 -
Sorafenib and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer
|
Phase 2 | |
Completed |
NCT00025337 -
Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated
|
Phase 3 | |
Recruiting |
NCT04642924 -
SGM-101 in Locally Advanced and Recurrent Rectal Cancer
|
Phase 2/Phase 3 | |
Completed |
NCT01846520 -
Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, Urologic and Lung Cancers
|
N/A | |
Completed |
NCT01217450 -
Selumetinib and Cetuximab in Treating Patients With Refractory Solid Tumors
|
Phase 1 | |
Completed |
NCT01191684 -
Vaccine Therapy in Treating Patients With Colorectal, Stomach, or Pancreatic Cancer
|
Phase 1 | |
Terminated |
NCT01233505 -
Veliparib, Oxaliplatin, and Capecitabine in Treating Patients With Advanced Solid Tumors
|
Phase 1 | |
Terminated |
NCT01238965 -
Panobinostat and Fluorouracil Followed By Leucovorin Calcium in Treating Patients With Stage IV Colorectal Cancer Who Did Not Respond to Previous Fluorouracil-Based Chemotherapy
|
Phase 1 | |
Terminated |
NCT01285102 -
Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer
|
Phase 1 | |
Completed |
NCT01037790 -
Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer
|
Phase 2 | |
Completed |
NCT00551421 -
Pertuzumab and Cetuximab in Treating Patients With Previously Treated Locally Advanced or Metastatic Colorectal Cancer
|
Phase 1/Phase 2 | |
Completed |
NCT00407654 -
VEGF Trap in Treating Patients With Previously Treated Metastatic Colorectal Cancer
|
Phase 2 | |
Completed |
NCT00091182 -
Oxaliplatin in Treating Young Patients With Recurrent Solid Tumors That Have Not Responded to Previous Treatment
|
Phase 2 | |
Terminated |
NCT00052585 -
Gefitinib and Combination Chemotherapy in Treating Patients With Advanced or Recurrent Colorectal Cancer
|
Phase 2 | |
Completed |
NCT00023933 -
Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Recurrent or Persistent Metastatic Colorectal Cancer
|
Phase 1 | |
Not yet recruiting |
NCT05076305 -
PelvEx 4: Advanced Pelvic Malignancy and the Role of the Multi-disciplinary Team Meeting
|
||
Completed |
NCT01740648 -
Trametinib, Fluorouracil, and Radiation Therapy Before Surgery in Treating Patients With Stage II-III Rectal Cancer
|
Phase 1 | |
Terminated |
NCT00397878 -
AZD0530 (NSC 735464) in Treating Patients With Previously Treated Metastatic Colon Cancer or Rectal Cancer
|
Phase 2 | |
Completed |
NCT00100841 -
Phase II Trial of FOLFOX6, Bevacizumab and Cetuximab in Patients With Colorectal Cancer
|
Phase 2 |