WithdrawnNCT00571740Updated Jul 6, 2016

Cetuximab and Bevacizumab as First-Line Therapy Followed By Combination Chemotherapy and Bevacizumab With or Without Cetuximab as Second-Line Therapy in Treating Patients With Stage IV Colorectal Cancer

A Phase 2 interventional study of bevacizumab and cetuximab in Colorectal Cancer, sponsored by Alliance for Clinical Trials in Oncology. Withdrawn. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-07-06.

Sponsored by Alliance for Clinical Trials in Oncology · Phase 2, Interventional, and Treatment

Why this study was withdrawn

The study was not activated

Phase: Phase 2
Study type: Interventional
Enrollment: 0
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

RATIONALE: 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 carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibodies together with combination chemotherapy may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving cetuximab together bevacizumab works as first-line therapy, followed by combination chemotherapy and bevacizumab with or without cetuximab as second-line therapy in treating patients with stage IV colorectal cancer.

Read the detailed description

OBJECTIVES:

Primary

To assess the efficacy of bevacizumab and cetuximab as first-line treatment for metastatic colorectal cancer, as measured by percentage of patients who remain progression-free at 6 months.

Secondary

To evaluate adverse events, confirmed response, duration of response, time to disease progression, time to treatment failure, and survival of patients treated with bevacizumab and cetuximab.
To evaluate adverse events, confirmed response, duration of response, time to disease progression, time to treatment failure, and survival of patients who are refractory to dual-agent bevacizumab and cetuximab and are subsequently treated with modified FOLFOX7 chemotherapy and bevacizumab with or without cetuximab.
To evaluate quality of life parameters in patients treated with these regimens.
To estimate the direct medical resource utilization and costs.
To assess the reliability of FDG-PET as a measurement of early treatment response, as measured by percentage of patients who are progression-free at 6 months.
To identify circulating angiogenesis biomarkers.
To assay the activity of pro-angiogenic factors in plasma angiogenic assays.

OUTLINE: This is a multicenter study*. Patients are stratified according to ECOG performance status (0-1 vs 2) and number of metastatic sites (1 vs > 1).

NOTE: *Participating site must be PET-qualified.

First-line therapy: Patients receive bevacizumab IV over 30-90 minutes and cetuximab IV over 2 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients with progressive disease proceed to second-line therapy.
Second-line therapy: Patients are randomized* to 1 of 2 treatment arms.
- Arm I (modified FOLFOX7 with bevacizumab only): Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
- Arm II (modified FOLFOX7 with bevacizumab and cetuximab): Patients receive bevacizumab and modified FOLFOX7 as in arm I. Patients also receive cetuximab IV over 2 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

NOTE: *Randomization occurs prior to receiving first-line therapy.

Patients undergo blood sample collection periodically for translational studies. Samples are analyzed for circulating endothelial cells and endothelial progenitor cells via flow cytometry; angiogenic activity of serum/plasma in angiogenesis-dependent diseases via endothelial proliferation assay and matrigel tube formation assay; and circulating angiogenesis biomarkers (i.e., free VEGF, soluble FLT-1, and KDR) via ELISA.

Quality of life is assessed periodically using the UNISCALE, Skindex-16, and Skin Assessment Questionnaires.

After completion of study treatment, patients are followed every 6 months for up to 3 years.

Conditions studied

Colorectal Cancer

Browse trials for

Colorectal Neoplasms 5,599

Keywords

stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

In context

Colorectal Neoplasms

5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,459 are open to participants now.

Browse Colorectal Neoplasms studies →

Lead sponsor

Alliance for Clinical Trials in Oncology is the lead sponsor of 499 studies on the registry; 27 are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

DISEASE CHARACTERISTICS:

Histologically confirmed stage IV colorectal cancer
Measurable disease, defined as at least one lesion whose longest diameter can be accurately measured as ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan
Must not be a candidate for neoadjuvant therapy
No CNS or brain metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 12 weeks
ANC ≥ 1,500/mm\^3
Platelet count ≥ 100,000/mm\^3
Hemoglobin ≥ 10.0 g/dL
Total bilirubin \< 1.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 3 times ULN
AST ≤ 3 times ULN
Creatinine ≤ 1.5 x times ULN
Proteinuria \< 1+ by urinalysis OR proteinuria \< 1 g by 24-hour urine collection
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
English-speaking patients must have the ability to complete questionnaires by themselves or with assistance
Must be willing to provide blood and tissue samples for research purposes
No history of hypertensive crisis or hypertensive encephalopathy
No blood pressure > 150/100 mm Hg
No New York Heart Association (NYHA) class II-IV congestive heart failure
No myocardial infarction or unstable angina within the past 6 months
No stroke or transient ischemic attack within the past 6 months
No clinically significant vascular disease (e.g., aortic aneurysm or aortic dissection)
No clinically significant peripheral vascular disease
No evidence of bleeding diathesis or coagulopathy
No significant traumatic injury within the past 28 days
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
No serious nonhealing wound, ulcer, or bone fracture

PRIOR CONCURRENT THERAPY:

No prior nonsurgical treatment for stage IV disease
- Adjuvant therapy allowed if completed > 6 months prior to study registration
More than 4 weeks since prior and no concurrent or planned participation in another experimental drug study
No prior therapy that specifically and directly targets the EGFR pathway
No prior monoclonal antibody therapy
More than 28 days since prior major surgery or open biopsy
More than 7 days since prior minor surgery, such as fine-needle aspirations or core biopsies
- Placement of a vascular access device does not have to meet this criterion
No concurrent major surgery

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 0 participants (actual)

Study arms

Active comparator
Arm I (second-line therapy)
Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab · Drug: fluorouracil · Drug: leucovorin calcium · Drug: oxaliplatin
Experimental
Arm II (second-line therapy)
Patients receive bevacizumab and modified FOLFOX7 as in arm I. Patients also receive cetuximab IV over 2 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab · Biological: cetuximab · Drug: fluorouracil · Drug: leucovorin calcium · Drug: oxaliplatin

Interventions

Biologicalbevacizumab
Given IV
Biologicalcetuximab
Given IV
Drugfluorouracil
Given IV
Drugleucovorin calcium
Given IV
Drugoxaliplatin
Given IV

What researchers measure

Primary outcomes

Progression-free survival (PFS) rate at 6 months
Time frame: at 6 months

Secondary outcomes

Tumor response rate associated with second-line therapy
Time frame: up to 3 years
Time to progression during second-line therapy
Time frame: up to 3 years
Duration of response
Time frame: up to 3 years
Quality of life
Time frame: up to 3 years

Study locations

No study locations are listed for this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 6, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00571740
Lead sponsor: Alliance for Clinical Trials in Oncology
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Dec 12, 2007
Last update: Jul 6, 2016

Study contacts

Axel Grothey, MD

study chair · Mayo Clinic

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is withdrawn, as verified in Jul 2016. You cannot join it, but the record below documents what was studied.

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