Trial Information

FOxTROT - Fluoropyrimidine, Oxaliplatin and Targeted Receptor Pre-Operative Therapy: a Controlled Trial in High-Risk Operable Colon Cancer

OBJECTIVES:

Primary

- To determine if neoadjuvant chemotherapy with or without panitumumab followed by
deferred surgery and completion of chemotherapy postoperatively can reduce the 2-year
recurrence as compared to surgery and postoperative chemotherapy with or without
panitumumab.

- To determine if adding panitumumab in the neoadjuvant treatment produces a measurable
increase in antitumor efficacy as measured by tumor shrinkage.

Secondary

- To assess the accuracy of pre-treatment CT scan staging.

- To assess the tolerability of the neoadjuvant therapies.

- To assess the nature and frequency of surgical complications.

- To measure the impact of the treatments on quality of life and on resource usage.

OUTLINE: This is a multicenter study. Patients are stratified according to age (< 50 year vs
50-59 years vs 60-69 years vs ≥ 70 years), radiological T-stage (T3 vs T4), radiological
nodal status (Nx vs N0 vs N1 vs N2), site of primary tumor, proposed chemotherapy (OxMdG vs
OxCap), and defunctioning colostomy (yes vs no).

Patients receive 1 of the 2 following treatment regimens:

- OxMdG: Patients receive oxaliplatin IV and folinic acid IV over 2 hours followed by
fluorouracil IV continuously over 46 hours on day 1 for 1 course.

- OxCap: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine
twice daily on days 1-15 for 1 course.

Patients are then randomized to 1 of 2 treatment arms.

- Neoadjuvant therapy:

- Arm I: Patients receive 1 of the following chemotherapy regimens:

- OxMdG: Patients receive oxaliplatin IV over 2 hours and fluorouracil IV
continuously over 46 hours on day 1. Treatment repeats every 2 weeks for 3
courses in the absence of disease progression or unacceptable toxicity.

- OxCap: Patients receive oxaliplatin IV over 2 hours on day 1 and oral
capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 2
courses in the absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive 1 of the following regimens:

- OxMdG + panitumumab: Patients receive panitumumab IV over 60 minutes on day 1
followed by oxaliplatin IV over 2 hours and fluorouracil IV continuously over
46 hours on day 1. Treatment repeats every 2 weeks for 3 courses in the
absence of disease progression or unacceptable toxicity.

- OxCap + panitumumab: Patients receive panitumumab IV over 60 minutes on day 1
followed by oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice
daily on days 1-15. Treatment repeats every 3 weeks for 2 courses in the
absence of disease progression or unacceptable toxicity.

Approximately 52 days after beginning chemotherapy, patients in both arms proceed to
surgery.

- Surgery: Patients in both arms undergo surgical resection of the primary tumor.

- Adjuvant therapy: Beginning 4-8 weeks after completion of surgery, patients receive
adjuvant treatment on the same arm for which they received neoadjuvant therapy.

- Arm I: Patients receive either nine 2-week courses of OxMdG therapy or six 3-week
courses of OxCap therapy.

- Arm II: Patients receive twelve 2-week courses of OxMdG therapy concurrently with
panitumumab given every 2 weeks OR eight 3-week courses of OxCap therapy
concurrently with panitumumab given every 3 weeks.

Tumor tissue is collected during surgery and blood samples are collected periodically for
biomarker studies. Samples are analyzed for the detection of k-ras mutations; the detection
of EGFR expression and/or functional genetic polymorphisms of the EGFR gene via PCR; the
detection of copy number EGFR gene amplification via fluorescence in situ hybridization
(FISH); the detection of EGFR activation via immunohistochemistry (IHC); the detection of
EGFR by downstream parameters via western blotting and/or gene expression microarray
techniques; for proteomics; and for epigenetics.

Patients complete quality of life questionnaires at baseline, at first course of
postoperative chemotherapy, and at 1 year following randomization.

After completion of study treatment, patients are followed every 6 months for 3 years and
then annually thereafter.