Clinical trial NCT00831181: Neo-adjuvant Chemoradiation With Oxaliplatin/5-FU in Rectal Cancer
Official title: A Phase II Open-labeled, Prospective Study to Determine the Efficacy of Preoperative Chemoradiation With Oxaliplatin/5-FU in Locally Advanced Rectal Cancer Followed by Total Mesorectal Excision and FOLFOX6
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage II rectal cancer
stage III rectal cancer
adenocarcinoma of the rectum
Lead sponsor: Beth Israel Medical Center
Sponsor class: OTHER
First posted: 2009-01-28
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: 5FU based neoadjuvant chemoradiation (nCRT) is the standard of care for Stage II/III rectal cancer. Pathologic complete response (pCR) and downstaging have been associated with improved outcomes. The addition of oxaliplatin (OXA) to neoadjuvant therapy may reduce distant disease recurrence. Adjuvant treatment with OXA for rectal cancer has been motivated by benefits demonstrated in stage III colon cancer.

Objective: To determine the feasibility, toxicity, and efficacy of preoperative OXA/5FU and RT followed by total mesorectal excision (TME) and adjuvant

PURPOSE: This phase II trial is studying the side effects and how well giving neo-adjuvant combination chemotherapy with radiation works in treating patients undergoing surgery for rectal cancer.

Detailed description: OBJECTIVES:

Primary

* To assess the complete pathologic response rate in patients with rectal cancer treated with radiation, modified neoadjuvant FOLFOX 6 chemotherapy followed by total mesorectal excision and adjuvant modified FOLFOX 6 chemotherapy.

Secondary

* To observe the overall pathologic response rate in these patients.
* To correlate pathologic staging with preoperative ultrasound and pelvic MRI staging.
* To assess toxic side effects of these regimens in these patients.
* To assess patterns of disease relapse, disease-free survival outcomes, and overall survival outcomes of these patients.

OUTLINE:

Patients with stage II/III rectal cancer were treated with OXA 60mg/m2 weekly continuous infusion 5FU of 225 mg/m2/d d1-5 with pelvic RT of 1.8Gy/d for 28 doses. Adjuvant therapy consisted of 6 cycles of biweekly FOLFOX6.

Surgery: Patients undergo total mesorectal excision by anterior resection or an abdominal perineal resection within 4 weeks after completion of neoadjuvant therapy.

Adjuvant therapy: Within 4 weeks after surgery, patients receive modified FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium IV over 2 hours on day 1 and continuous fluorouracil IV over 46 hours on days 1-2. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life assessment questionnaires at baseline and at each follow-up visit.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.

Eligibility criteria: Inclusion Criteria

* Histologically proven adenocarcinoma of the rectum with no distant metastases.
* T3-4N0M0, TanyN1-3M0 assessed by clinical exam, TRUS, MRI and CT
* The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of the anal verge by protoscopic examination.
* No prior chemotherapy or pelvic irradiation.
* ECOG performance status 0-1
* Age 18 to 70 years
* ANC \>= 1500/mm3 and platelets \>= 100,000/mm3
* Serum creatinine \<= 1.5 x ULN; bilirubin \<= 1.5 x ULN; ALT\<= 2.5 x ULN

Exclusion Criteria

* Pregnant or lactating females; patients not practicing active contraception while sexually active.
* No other serious medical condition
* A psychiatric disorder that would prohibit the subject from participating fully.
* Peripheral neuropathy \> grade 1
* History within the past 5 years of a cancer diagnosis except for non-melanomatous skin cancers or in situ cervix carcinoma.
* HIV positive patients

Primary outcomes:
measure: Pathologic Response and Complete Response
timeFrame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, an average of 3.5 months
Secondary outcomes:
measure: Treatment Toxicity
timeFrame: Weekly during chemoradiation treatment (3 months). Bi-weekly during adjuvant FOLFOX therapy (3.5 months).
measure: Complete Resectability Rates
timeFrame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment.
measure: Local Regional Control
timeFrame: median follow-up 22 months post-TME
measure: Disease-free Survival
timeFrame: median 22 months follow-up
measure: Overall Survival
timeFrame: median follow-up 22 months
measure: Patterns of Disease Failure, Including Local Recurrence and Distant Metastasis Assessed by CT Scan
timeFrame: median follow-up 22 months
measure: Number of Participants With Comparison of Preoperative Stage With Post-treatment Pathologic Stage
timeFrame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment.
Other outcomes:
Locations:
city: New York
country: United States
facility: Beth Israel Medical Center - Philipps Ambulatory Care Center
state: New York
city: New York
country: United States
facility: St. Luke's-Roosevelt Hospital Center - Roosevelt Division
state: New York
Study officials:
affiliation: Beth Israel Medical Center
name: Peter Kozuch, MD
role: PRINCIPAL_INVESTIGATOR
References: