CALGB C80702- A PHASE III TRIAL OF 6 VERSUS 12 TREATMENTS OF ADJUVANT FOLFOX PLUS CELECOXIB OR PLACEBO FOR PATIENTS WITH RESECTED STAGE III COLON CANCER
Initiation of treatment must begin within 14 days after randomization. While not
strictly an eligibility criterion, it is strongly recommended that patients begin
treatment between 21 - 56 days after surgery. For patients who fall outside of this
range or for any treatment-related questions, contact the CALGB or SWOG Study Chair.
This is a randomized, double-blind trial. No blinded starter supplies will be available
for this study. Initial blinded, patient-specific clinical supplies of celecoxib / placebo will be shipped from the Pharmaceutical Management Branch (PMB) to the registering
investigator at the time of patient randomization and should arrive within 7 to 10 days of
randomization (see Section 9.7).
One cycle will be defined as 14 days of treatment. Cytotoxic chemotherapy will consist of
6 or 12 cycles of FOLFOX and daily celecoxib/placebo. Celecoxib/placebo will start by
Day 1 of cycle 2 of FOLFOX.
Requirements for tumor parameters
1.1. Histologically documented adenocarcinoma of the colon. The gross inferior
(caudad) margin of the primary tumor must lie above the peritoneal reflection
(i.e., patients with rectal cancer are not eligible). Surgeon confirmation that the
entire tumor was above the peritoneal reflection is only required in cases where it
is important to establish if the tumor is a rectal or colon primary.
1.2. Tumors must have been completely resected. In patients with tumor adherent to
adjacent structures, en bloc Ro resection must be documented in the operative
report. Near or positive radial margin are not exclusions as long as en bloc
resection was performed. Positive proximal margin or distal margin is an
1.3. Node positive disease (N1 or N2) as designated in AJCC version 7. Either at least
one pathologically confirmed positive lymph node or N1C (defined as tumor
deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal
tissues without regional lymph node metastases). Patients with resected stage IV
disease are not eligible.
1.4. No evidence of residual involved lymph node disease or metastatic disease at the
time of registration.
1.5. Patients with synchronous colon cancers are eligible and staging for stratification
will be based on higher N stage of the more advanced primary tumor. However,
patients with synchronous colon and rectal primary tumors are not eligible.
2. Patients are ineligible if they plan on regular use of NSAIDs at any dose more than 2
times per week (on average) or aspirin at more than 325 mg at least three times per
week, on average. Low-dose aspirin not exceeding 100 mg/day is permitted. Patients
who agree to stop regular NSAIDs or higher dose aspirin are eligible and no wash out
period is required.
3. No previous or concurrent malignancy, except treated basal cell or squamous cell
cancer of skin, treated in situ cervical cancer, treated lobular or ductal carcinoma in
situ in one breast, or any other cancer for which the patient has been disease-free for
at least 5 years.
4. No neurosensory or neuromotor toxicity >= grade 2 at the time of registration.
5. No known allergy to platinum compounds.
6. No prior allergic reaction or hypersensitivity to sulfonamides, celecoxib or NSAIDs.
7. No history of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or
upper gastrointestinal perforation within the past 3 years. Patients with ulceration,
bleeding or perforation in the lower bowel are not excluded.
8. No symptomatic pulmonary fibrosis or interstitial pneumonitis >= grade 2.
9. No cardiac risk factors including:
* Uncontrolled high blood pressure (systolic blood pressure > 150).
* Unstable angina.
* History of documented myocardial infarction or cerebrovascular accident.
* New York Heart Association class III or IV heart failure.
10. Non-pregnant and not nursing. Men and women of childbearing potential must agree
to employ adequate contraception for the duration of chemotherapy and for as many
as 8 weeks after the completion of chemotherapy due to the unknown teratogenic
effects of FOLFOX on the developing fetus.
11. ECOG performance status 0, 1, or 2.
12. Age at least 18 years.
13. Required initial laboratory values
Granulocytes >= 1,500/[MICRO-SYMBOL]L
Platelet count >= 100,000/[MICRO-SYMBOL]L
Creatinine <= 1.5 x upper limit of normal
Bilirubin <= 1.5 x upper limit of normal