Celebrex With Preoperative Chemoradiation - Rectal Cancer

Condition(s) targeted: Colorectal Neoplasms

Intervention: Celecoxib (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: University Health Network, Toronto

Official(s) and/or principal investigator(s):
John Kim, MD, Principal Investigator, Affiliation: Princess Margaret Hospital, Canada

Overall contact:
John Kim, MD, Phone: 416-946-2126, Email: john.kim@rmp.uhn.on.ca

Colorectal carcinoma is the third most common cause of death from cancer. Approximately, 30% of colorectal carcinomas involve the rectum. Optimizing local control in the pelvis while reducing treatment toxicity remains one of the principal goals of therapy for patients with locally advanced rectal carcinoma. Treatment strategies that achieve this goal will have a significant impact on our society. C linical trials have shown that this type of cancer is less likely to come back if chemotherapy and radiotherapy are added to surgery. A combination of all three types of therapy is now standard.

Celecoxib (Celebrex®) is a drug that lessens the action of an enzyme called cyclooxygenase-2 (COX-2) also known as a "COX-2 inhibitor". It is an anti-inflammatory capsule (drug that reduces irritation) that is commonly used to treat arthritis. It is not a chemotherapy drug. Laboratory experiments have shown that such COX-2 inhibitors may increase the anti-cancer effect of radiotherapy, without increasing radiation side effects. This has not yet been confirmed in humans. The main purpose of this study is to confirm that celecoxib does not increase the side effects when given with radiotherapy and chemotherapy for rectal cancer. We shall also be looking at how effective the combination of radiotherapy, chemotherapy and celecoxib is in shrinking rectal cancer.

Official title: A Phase I/II Trial of Celecoxib With Preoperative Chemoradiation for Resectable Rectal Cancer With In Vivo Analysis of Celecoxib Effector Pathways

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome:

- To assess the safety of celecoxib at a maximum dose of 400 mg orally twice daily in combination with preop RT and continuous infusional 5-FU. Incidence of dose-limiting toxicity (DLT) will be determined.

- To determine the efficacy of celecoxib in combination with preop RT and continuous infusional 5-FU. Pathologic complete response rate (pCR) will be used as the endpoint.

Secondary outcome:

Failure rate – locoregional and distant

Survival rate – disease-free and overall

Wound complication rate

Late toxicity incidence (RTOG criteria))

Sphincter preservation rate

Quality of life (FACT, EORTC)

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- patients with resectable or potentially resectable adenocarcinoma of the rectum

- clinical stage T2 N1-2 or T3-4 N0-2 (patients who require diverting loop colostomy

are eligible)

- age greater than 18 years, ECOG performance status < 2 (appendix, section 13. 1)

- biopsy proven adenocarcinoma, superior margin of the tumour within 15cm of the anal

verge on rigid sigmoidoscopy

Exclusion Criteria:

- Distant metastasis, Prior pelvic irradiation, Inflammatory bowel disease, Medical

conditions which preclude radical therapy

- History of malignancy within five years (except nonmelanoma skin cancer, CIN cervix)

- Pregnancy

- Hypersensitivity to celecoxib, NSAID, sulfonamides or 5-FU

- Significant comorbid illness

- History of peptic ulcer disease or NSAID-related gastrointestinal bleeding

- Use of aspirin, other NSAID or coxib in the two weeks prior to study entry

- Neutrophil count <1. 5x109/L, platelet count <100x109/L, serum bilirubin >1. 25xULN

(upper limit of normal), AST/ALT >3xULN, serum creatinine >1. 25xULN

John Kim, MD, Phone: 416-946-2126, Email: john.kim@rmp.uhn.on.ca

Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada; Recruiting
John Kim, MD, Phone: 416-946-2126, Email: john.kim@rmp.uhn.on.ca
John Kim, MD, Principal Investigator

Starting date: March 2004
Last updated: September 12, 2005