Celecoxib, Leucovorin, Fluorouracil, and Oxaliplatin in Treating Patients With Metastatic Colorectal Cancer

Sponsor

GERCOR - Multidisciplinary Oncology Cooperative Group (Other)

Overall Status

Unknown status

CT.gov ID

NCT00072553

Collaborator

(none)

Location

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as leucovorin, fluorouracil, and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of colorectal cancer by stopping blood flow to the tumor and by blocking the enzymes necessary for tumor cell growth. Combining chemotherapy with celecoxib may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining celecoxib with leucovorin, fluorouracil, and oxaliplatin in treating patients who have metastatic colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: celecoxib Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the response rate in patients with metastatic colorectal cancer treated with celecoxib, leucovorin calcium, fluorouracil, and oxaliplatin.

Secondary

Determine the toxicity of this regimen in these patients.
Determine the time of disease control to evaluate progression-free survival in patients treated with this regimen.
Determine the salvage surgery rate in patients treated with this regimen.
Determine the duration of chemotherapy-free intervals in patients treated with this regimen.
Determine the tolerability of this regimen in these patients.
Determine the quality of life of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive FOLFOX7 chemotherapy comprising 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. Patients also receive oral celecoxib twice daily beginning on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease stop treatment. If disease progression occurs during the chemotherapy-free interval, patients receive an additional 6 courses.

Patients with responding disease after receiving at least 6 courses of chemotherapy may undergo surgery. Beginning within 10 weeks after surgery, patients receive simplified LV5FU2 chemotherapy comprising leucovorin calcium IV over 2 hours on day 1, fluorouracil IV over 46 hours beginning on day 1, and oral celecoxib twice daily beginning on day 1. Treatment repeats every 14 days for at least 12 courses.

Quality of life is assessed at baseline, during courses 4 and 6, and then every 2 months thereafter.

Patients are followed at 1 month and then every 2 months thereafter.

PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Of An Optimized LV-5FU-Oxaliplatin Strategy With Celebrex In Metastatic Colorectal Cancer, Optimox2-Celecoxib Study

Study Start Date :

Sep 1, 2003

Outcome Measures

Primary Outcome Measures

Response rate []

Secondary Outcome Measures

Toxicity []
Time of disease control (progression-free survival) []
Salvage surgery rate []
Duration of chemotherapy-free intervals []
Tolerability []
Quality of life []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the colon or rectum
Metastatic disease
Inoperable disease (i.e., not suitable for complete carcinological surgical resection)
Measurable disease or nonmeasurable disease
At least 1 unidimensionally measurable lesion at least 20 mm by conventional CT scan OR 10 mm by spiral CT scan
Nonmeasurable disease defined as all other lesions, including small lesions or truly nonmeasurable disease
No CNS metastases
No exclusive bone metastases
No symptomatic ascites or pleural effusion not evacuated before study entry

PATIENT CHARACTERISTICS:

Age

18 to 75

Performance status

WHO 0-2

Life expectancy

Not specified

Hematopoietic

Neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
No known significant bleeding disorder

Hepatic

Alkaline phosphatase less than 3 times upper limit of normal (ULN)

Renal

Creatinine less than 1.5 times ULN OR
Creatinine clearance at least 30 mL/min
No uncontrolled hypercalcemia

Cardiovascular

No congestive heart failure

Gastrointestinal

No total or partial bowel obstruction
No active gastric or duodenal ulceration or gastrointestinal bleeding within the past year
No active inflammatory bowel disease

Other

Not pregnant or nursing
Fertile patients must use effective contraception
HIV negative
No peripheral sensory neuropathy
No known sensitivity to celecoxib, other COX-2 inhibitors, NSAIDs, salicylates, or sulfonamides
No AIDS-related illness
No active infection
No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or basal cell or squamous cell skin cancer
No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

No prior immunotherapy for metastatic disease

Chemotherapy

Prior adjuvant chemotherapy allowed provided the progression-free interval after completion of therapy is more than 6 months in duration
No prior chemotherapy for metastatic disease
No prior adjuvant oxaliplatin
No other concurrent chemotherapy

Endocrine therapy

No concurrent chronic oral or IV corticosteroid use (i.e., 2 weeks or longer in duration)

Radiotherapy

No concurrent radiotherapy

Surgery

Not specified

Other

More than 30 days since prior investigational drugs
No other concurrent investigational drugs or treatments
No concurrent prophylactic fluconazole
No concurrent chronic full-dose aspirin (at least 325 mg/day), other nonsteroidal anti-inflammatory drugs (NSAIDs), or other cyclooxygenase (COX)-2 inhibitors
Concurrent low-dose (cardioprotective) aspirin (80 mg/day or equivalent) allowed
No concurrent lithium
No other concurrent anticancer therapy