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A Phase II Trial of 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) Chemotherapy Plus Bevacizumab for Patients With Unresectable Stage IV Colon Cancer and a Synchronous Asymptomatic Primary Tumor

Phase 2
18 Years
Not Enrolling
Colorectal Cancer

Thank you

Trial Information

A Phase II Trial of 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) Chemotherapy Plus Bevacizumab for Patients With Unresectable Stage IV Colon Cancer and a Synchronous Asymptomatic Primary Tumor



- Determine the rate of major morbidity in patients with unresectable stage IV colon
cancer and a synchronous asymptomatic primary tumor treated with fluorouracil,
leucovorin calcium, and oxaliplatin (mFOLFOX6) in combination with bevacizumab without
resection of the primary tumor.


- Determine the rate of specific events related to the intact primary tumor requiring
hospitalization or a major intervention but not requiring surgery.

- Determine the rate of ≥ grade 3 toxicity as defined by the Common Terminology Criteria
for Adverse Events version 3.0 (CTCAE v3.0) that is related to study therapy prior to
disease progression.

- Determine overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV given concurrently with
leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours
on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years after
study entry.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.

Inclusion Criteria


- Histologically or cytologically confirmed adenocarcinoma of the colon

- No histological findings other than adenocarcinoma of the colon

- If the primary colon tumor and the metastatic lesions have been identified at
the same time and it is not possible to biopsy the colonic lesion, the patient
will be eligible without histologic confirmation of the primary cancer of the
colon as long as other radiographic studies or scans document the
characteristics of a colon cancer AND the biopsy of a metastatic site confirms
diagnosis of adenocarcinoma suggestive of a primary tumor of the colon

- Unresected primary tumor of the colon AND radiographically confirmed metastatic colon
cancer (single or multiple sites of metastases) that are not considered surgically
resectable for cure by chest imaging and CT scan or MRI of the abdomen within the
past 4 weeks and by endoscopy within the past 8 weeks

- Asymptomatic primary tumor

- No obstruction, perforation, or active bleeding requiring transfusion

- Distal extent of the tumor must be ≥ 12 cm from the anal verge on endoscopy

- Not a candidate for curative surgical resection of all metastatic and colon primary

- No evidence of Central Nervous System (CNS) metastases

- No recurrent local or metastatic disease after prior adjuvant therapy

- No diagnosis of rectal carcinoma


- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Absolute neutrophil count ≥ 1200/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times
ULN if liver metastases are present)

- Alkaline phosphatase ≤ 3.0 times ULN (≤ 5.0 times ULN if liver metastases are

- Bilirubin ≤ 1.5 times ULN (≤ 2.0 times ULN if liver metastases are present)

- Creatinine < 1.8 mg/dL

- Urine dipstick indicating 0-1+ protein

- If dipstick reading is ≥ 2+, a 24-hour urine collection must demonstrate < 1 g
of protein

- Prothrombin Time and International Normalized Ratio (PT/INR) ≤ 1.5 unless the patient
is on therapeutic doses of warfarin, in which case the following criteria must be

- Patient must have an in-range INR (between 2 and 3) on a stable dose of warfarin

- Patient must not have active bleeding or a pathologic condition that is
associated with a high risk of bleeding

- Patients with a history of non-colorectal malignancies must be disease free for ≥ 5
years prior to study entry and be deemed at low risk for recurrence

- Patients with the following cancers are eligible if diagnosed and treated within the
past 5 years:

- Carcinoma in situ of the colon

- Melanoma in situ

- Basal cell or squamous cell carcinoma of the skin

- Carcinoma in situ of the cervix

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after the
completion of study therapy

- No uncontrolled blood pressure (BP), defined as BP > 150/100 mm Hg

- No nonmalignant systemic disease that would preclude any of the study therapy drugs,
compromise the safety of the patient, or inhibit the patient's ability to participate
in the study, including any of the following:

- New York Heart Association class III or IV cardiac disease

- Myocardial infarction within the past 6 months

- Unstable angina within the past 6 months

- Symptomatic arrhythmia

- No transient ischemic attack or cerebrovascular accident within the past 6 months

- No symptomatic peripheral vascular ischemia within the past 6 months

- No arterial thrombotic event within the past 6 months

- No gastroduodenal ulcer(s) determined by endoscopy to be active

- No gastrointestinal perforation within the past 12 months

- No serious or nonhealing wound, skin ulcer, or bone fracture

- No significant traumatic injury within the past 28 days

- No significant episodes of acute bleeding requiring blood transfusion within the past
6 months

- No clinically significant (≥ grade 2) peripheral neuropathy (neurosensory or
neuromotor toxicity)

- No pulmonary fibrosis or interstitial pneumonitis by chest x-ray

- No psychiatric or addictive disorders or other conditions that would preclude the
patient from meeting study requirements


- See Disease Characteristics

- No prior systemic chemotherapy, radiation therapy, or surgery for this malignancy

- No prior endoscopic management of this malignancy other than biopsy, including
endoscopic stent placement, fulguration, or laser treatment

- More than 30 days since prior investigational drugs

- More than 28 days since prior major surgical procedure or open biopsy

- More than 7 days since prior core biopsy or other minor procedure, excluding
placement of a vascular access device

- No concurrent major surgery unrelated to intact primary colon cancer

- No concurrent radiotherapy

- No concurrent filgrastim (G-CSF) or pegfilgrastim as primary prophylaxis for

- No concurrent halogenated antiviral agents

- No other concurrent investigational drugs

- No other concurrent antineoplastic agents

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Major Morbidity Related to the Intact Primary Tumor

Outcome Description:

Cumulative incidence was used to compute percent probability of morbidity. Cumulative incidence at time t measures the probability of a participant having an event (i.e., Colonic bleeding, perforation, bowel obstruction, or fistula formation requiring surgery or resulting in patient death) over the given duration, t. It involves computing the probability of an event at any observed time (i.e., the number of new cases during a period divided by the number of subjects at risk) and multiplying these successive probabilities by any early computed probability to get the final estimate.

Outcome Time Frame:

24 months

Safety Issue:


Principal Investigator

Norman Wolmark, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NSABP Foundation, Inc.


United States: Federal Government

Study ID:




Start Date:

March 2006

Completion Date:

December 2012

Related Keywords:

  • Colorectal Cancer
  • adenocarcinoma of the colon
  • stage IV colon cancer
  • Colonic Neoplasms
  • Colorectal Neoplasms



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