CompletedNCT00321828Updated Mar 21, 2024Results posted

Combination Chemotherapy and Bevacizumab in Treating Patients With Stage IV Colon Cancer That Cannot Be Removed By Surgery

A Phase 2 interventional study of bevacizumab and fluorouracil in Colorectal Cancer, sponsored by NSABP Foundation Inc. Completed at 163 sites in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2024-03-21.

Sponsored by NSABP Foundation Inc · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 90
Allocation: Not applicable
Ages: 18 Years to 120 Years
Sex: All

Study summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, 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. Bevacizumab may also stop the growth of colon cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bevacizumab works in treating patients with stage IV colon cancer that cannot be removed by surgery.

Read the detailed description

OBJECTIVES:

Primary

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.

Secondary

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.

Conditions studied

Colorectal Cancer

Browse trials for

Colonic Neoplasms 1,432

Keywords

adenocarcinoma of the colon
stage IV colon cancer

In context

Colonic Neoplasms

1,432 studies on the registry are indexed under Colonic Neoplasms; 357 are open to participants now.

This study's enrollment of 90 is close to the median of 90 across 1,034 interventional studies indexed under Colonic Neoplasms.

Browse Colonic Neoplasms studies →

Lead sponsor

NSABP Foundation Inc is the lead sponsor of 64 studies on the registry; 1 is open to participants now.

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

Who can participate

Ages eligible: 18 Years to 120 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

DISEASE CHARACTERISTICS:

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 tumors
No evidence of Central Nervous System (CNS) metastases
No recurrent local or metastatic disease after prior adjuvant therapy
No diagnosis of rectal carcinoma

PATIENT CHARACTERISTICS:

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 present)
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 met:
- 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

PRIOR CONCURRENT THERAPY:

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 neutropenia
No concurrent halogenated antiviral agents
No other concurrent investigational drugs
No other concurrent antineoplastic agents

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 90 participants (actual)

Study arms

Experimental
Arm 1: Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Biological: bevacizumab · Drug: fluorouracil · Drug: leucovorin · Drug: oxaliplatin

Interventions

Biologicalbevacizumab
bevacizumab 5 mg/kg IV on day 1 every 14 days until excessive toxicity or disease progression
Drugfluorouracil
5-FU 400 mg/m2 IV bolus over 2-4 minutes then 2400 mg/m2 IV continuous infusion over 46 hours on day 1 every 14 days until excessive toxicity or disease progression
Also known as: 5-FU
Drugleucovorin
leucovorin 400 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression
Also known as: leucovorin calcium
Drugoxaliplatin
Oxaliplatin 85 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression

What researchers measure

Primary outcomes

Major Morbidity Related to the Intact Primary Tumor
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.
Time frame: 24 months

Secondary outcomes

Local Complications as Assessed by Colonic Obstruction Requiring Hospitalization (But Not Surgery) for Medical Management, Stent Placement, Laser Treatment, or Fulguration
Time frame: Time from start of study through year 5
Local Complications as Assessed by Gastrointestinal Bleeding Requiring Transfusion But Not Requiring Surgery
Time frame: Time from start of study through year 5
Local Complications as Assessed by Fistula Formation (Self-draining Enterocutaneous Fistula and Intra-abdominal Abscess Requiring Percutaneous Drainage) Not Requiring Surgery
Time frame: Time from start of study through year 5
Local Complications as Assessed by Other Events Related to the Intact Primary Tumor Which Require Hospitalization But Not Surgery
Time frame: Time from start of study through year 5
Serious Adverse Events (Grades 3, 4, and 5) as Defined by CTCAE v3.0
Time frame: Time from start of study through year 5
Overall Survival as Measured by Death From Any Cause
Time frame: Time from start of study through year 5

Results

Posted Jan 14, 2013

Participant flow

Participant flow — Overall Study
Milestone	Arm 1: Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Started	90
Completed	86
Not completed	4
Withdrew: Ineligible	3
Withdrew: No follow up data	1

Outcome measures

PrimaryMajor Morbidity Related to the Intact Primary Tumor

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.

Time frame:: 24 months
Reported as:: Number · probability of major morbidity (%)

Major Morbidity Related to the Intact Primary Tumor
probability of major morbidity (%)	Arm 1: Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Major Morbidity Related to the Intact Primary Tumor	16.3 (7.6 to 25.1)

SecondaryLocal Complications as Assessed by Colonic Obstruction Requiring Hospitalization (But Not Surgery) for Medical Management, Stent Placement, Laser Treatment, or Fulguration

Time frame:: Time from start of study through year 5