Combination Chemotherapy and Bevacizumab With or Without RO4929097 in Treating Patients With Metastatic Colorectal Cancer

• Status: Withdrawn
• Trial end date: 2013-08-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Bevacizumab; Calcium; Fluorouracil; Leucovorin; Levoleucovorin; Oxaliplatin; R04929097

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the colon or adenocarcinoma of the rectum

• Metastatic disease by imaging

• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20mm by conventional techniques or as ≥ 10 mm by spiral CT scan

• No known brain metastases

• ECOG performance status 0-1

• ANC ≥ 1,500/mm³

• WBC ≥ 3,000/mm³

• Platelet count ≥ 100,000/mm³ (without a platelet transfusion ≤ 14 days prior to study)

• Hemoglobin ≥ 9 g/dL

• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)

• Urine protein:creatinine ≤ 0.5 or proteinuria < 1,000 mg on 24-hour urine collection

• Total bilirubin ≤ 1.5 times ULN

• AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN for patients with liver metastases)

• Albumin ≥ 2.5 g/dL

• Amylase ≤ 2 times ULN

• Lipase ≤ 2 times ULN

• PTT ≤ 1.2 times ULN

• INR ≤ 1.2 times ULN

• No patients with uncontrolled hypophosphatemia, hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia defined as less than the lower limit of normal for the institution, despite adequateelectrolyte supplementation

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use two forms of contraception (i.e., barrier contraception and one other method of contraception) prior to, during, and for ≥ 12 months after study participation

• Patients must not have current evidence of or history of another malignancy except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other curatively treated solid tumors with no evidence of disease for ≥ 3 years prior to enrollment

• Able to swallow capsules

• No malabsorption syndrome or other condition that would interfere with intestinal absorption

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma-secretase inhibitor RO4929097 used in the study

• No clinically important history of liver disease, including known viral, other hepatitis, or cirrhosis

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• A history of torsades de pointes or other significant cardiac arrhythmias

• Psychiatric illness and/or social situations that would limit compliance with study requirements

• No baseline QTcF > 450 msec (male) or QTcF > 470msec (female)

• No serious or non-healing wound, ulcer, or bone fracture

• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months

• No significant traumatic injury within the past 28 days

• No clinically significant cardiovascular disease, including any of the following:

• Inadequately controlled hypertension (systolic BP > 160 mm Hg and/or diastolic BP > 90 mm Hg despite antihypertension medication)

• History of cerebrovascular accident within the past 6 months

• Myocardial infarction or unstable angina within the past 6 months

• NYHA grade II-IV congestive heart failure

• Serious and inadequately controlled cardiac arrhythmia

• No requirement for antiarrhythmics or other medications known to prolong QTc

• No significant vascular disease (e.g., aortic aneurysm, requiring surgical repair, history of aortic dissection, or recent peripheral arterial thrombosis) within the past 6 months

• No clinically significant peripheral vascular disease

• No evidence of bleeding diathesis or coagulopathy

• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

• Recovered to < NCI CTCAE grade 2 toxicities related to prior therapy

• No prior adjuvant or neoadjuvant chemotherapy for colorectal cancers within 12 months of development of metastases

• No prior chemotherapy or gamma-secretase inhibitors or other investigational agents for metastatic colorectal cancer

• No prior radiotherapy for colorectal cancers including in the neoadjuvant or adjuvant setting within 12 months of development of metastases

• No major surgical procedure or open biopsy within the past 28 days and no anticipation of need for major surgical procedures during the course of the study

• No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)

• Patients who switch from warfarin sodium to alternative anti-coagulant agents allowed

• No concurrent medications that are strong inducers, inhibitors, or substrates of CYP3A4, including ketoconazole and grapefruit juice

• No concurrent combination antiretroviral therapy for HIV-positive patients