Completed

Bevacizumab and Cetuximab With or Without Irinotecan in Treating Patients With Irinotecan-Refractory Metastatic Colorectal Cancer

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What is being tested

cetuximab

+ bevacizumab
+ irinotecan hydrochloride
Biological
Drug
Other
Who is being recruted

Recurrent Colon Cancer
+3

+ Recurrent Rectal Cancer
+ Stage IVA Colon Cancer
Over 18 Years
How is the trial designed

Treatment Study

Phase 2
Interventional
Study Start: December 2003

Summary

Principal SponsorNational Cancer Institute (NCI)
Last updated: April 15, 2015
Sourced from a government-validated database.Claim as a partner
Study start date: December 1, 2003Actual date on which the first participant was enrolled.

This randomized phase II trial is studying giving bevacizumab and cetuximab together with irinotecan to see how well it works compared to giving bevacizumab and cetuximab alone in treating patients with irinotecan-refractory metastatic colorectal cancer. Monoclonal antibodies such as cetuximab and 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 deliver tumor -killing substances to them. Drugs used in chemotherapy, such as irinotecan, also work in different ways to kill tumor cells or stop them from growing. Giving cetuximab and bevacizumab together with irinotecan may improve the ability to block tumor growth. PRIMARY OBJECTIVES: I. Evaluate time to tumor progression in patients with irinotecan-refractory metastatic colorectal cancer treated with bevacizumab and cetuximab with or without irinotecan. II. Evaluate objective response rate in patients treated with these regimens. III. Evaluate overall survival of patients treated with these regimens. IV. Evaluate safety, tolerability, and adverse event profiles of these regimens in these patients. V. Correlate a panel of molecular markers (e.g., those involved in the epidermal growth factor receptor signaling pathway, angiogenic pathway, and irinotecan metabolism) with clinical outcome in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, ECOG performance status (0 vs 1), and albumin (> 3.0 g/dL vs ≤ 3.0 g/dL). Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36; bevacizumab IV over 30-90 minutes on days 1\*, 15, and 29 OR on days 1 and 22; and irinotecan IV over 30-90 minutes (at the same dose and schedule that the patient previously received) beginning on day 1. ARM B: Patients receive cetuximab as in Arm A and bevacizumab IV over 30-90 minutes on days 1\*, 15, and 29. NOTE: \*Bevacizumab is given on day 2 (instead of day 1) of course 1, and is given on day 1 of subsequent courses. In both arms, courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed for 3 years.

Official TitleA Randomized Phase II Study of Bevacizumab in Combination With Cetuximab Plus Irinotecan, or in Combination With Cetuximab Alone, in Irinotecan-Refractory Colorectal Cancer 
Principal SponsorNational Cancer Institute (NCI)
Last updated: April 15, 2015
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
70 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

None (Single-arm trial)
: If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment
: Everyone gets the same treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled
: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IVA Colon Cancer
Stage IVA Rectal Cancer
Stage IVB Colon Cancer
Stage IVB Rectal Cancer
Criteria

Inclusion Criteria: * Histologically or cytologically confirmed colorectal cancer * Metastatic disease by diagnostic imaging studies * Measurable disease * At least 1 unidimensionally measurable lesion with minimum lesion size at least twice the slice thickness of the imaging study used * Refractory to irinotecan, evidenced by clinical documentation * Received at least 1 prior irinotecan-containing chemotherapy regimen for metastatic disease and progressed during or within 6 weeks after completion of therapy * Must have received prior irinotecan according to 1 of the following schedules: * Weekly administration with a starting dose of 100-125 mg/m\^2 * Biweekly administration (every other week) with a starting dose of approximately 180 mg/m\^2 * Once every three weekly administration with a starting dose of 300-350 mg/m\^2 * No known brain metastases * No prior primary CNS tumors * Performance status - ECOG 0-1 * Performance status - Karnofsky 80-100% * More than 3 months * WBC \>= 3,000/mm\^3 * Absolute neutrophil count \>= 1,500/mm\^3 * Platelet count \>= 100,000/mm\^3 * Hemoglobin \>= 9 g/dL * No bleeding diathesis or coagulopathy * Bilirubin normal * AST and ALT =\< 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of known liver metastases) * INR \< 1.5 (for patients receiving warfarin) * Creatinine =\< ULN * Creatinine clearance ≥ 60 mL/min * No proteinuria * No prior stroke * No symptomatic congestive heart failure * No unstable angina pectoris * No uncontrolled hypertension * No clinically significant cardiac arrhythmia * None of the following arterial thromboembolic events within the past 6 months: * Myocardial infarction * Cerebrovascular accident * Transient ischemic attack * Unstable angina * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 3 months after study participation * No significant traumatic injury within the past 28 days * No grade 3 or greater neurotoxicity * No uncontrolled seizures * No prior allergic reactions attributed to compounds of similar chemical or biological composition to study agents * No prior irinotecan intolerance * No ongoing or active infection requiring parenteral antibiotics * No serious nonhealing active wound, ulcer, or bone fracture * No psychiatric illness or social situation that would preclude study compliance * No other concurrent uncontrolled illness that would preclude study participation * No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies * No prior cetuximab * No other prior epidermal growth factor receptor-directed therapy * No prior anticancer murine or chimeric monoclonal antibody therapy * Prior humanized monoclonal antibody therapy allowed * No prior bevacizumab * No other prior vascular endothelial growth factor-targeted therapy * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) * More than 4 weeks since prior radiotherapy * More than 28 days since prior major surgical procedure or open biopsy * Recovered from all prior therapy * Any number of prior standard or investigational regimens allowed * No other concurrent investigational agents * No other concurrent anticancer therapy * No recent or concurrent thrombolytic agents * No recent or concurrent full-dose warfarin except as required to maintain patency of preexisting, permanent indwelling IV catheters * No concurrent therapeutic heparin * Concurrent prophylactic low-molecular weight heparin allowed * No concurrent chronic daily aspirin (\> 325 mg/day) * No concurrent nonsteroidal anti-inflammatory medications known to inhibit platelet function * No concurrent combination antiretroviral therapy for HIV-positive patients


Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36; bevacizumab IV over 30-90 minutes on days 1\*, 15, and 29 OR on days 1 and 22; and irinotecan IV over 30-90 minutes (at the same dose and schedule that the patient previously received) beginning on day 1. NOTE: \*Bevacizumab is given on day 2 (instead of day 1) of course 1, and is given on day 1 of subsequent courses.
Group II
Experimental
Patients receive cetuximab as in Arm A and bevacizumab IV over 30-90 minutes on days 1\*, 15, and 29. NOTE: \*Bevacizumab is given on day 2 (instead of day 1) of course 1, and is given on day 1 of subsequent courses.
Study Objectives
Primary Objectives

Secondary Objectives

Survival probabilities will be computed using Kaplan-Meier methods and compared using the log-rank test.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 1 location
Suspended
Memorial Sloan-Kettering Cancer CenterNew York, United StatesSee the location

CompletedOne Study Center