S0304 Induct Chemo Then Chemo-RT in Pts w/Locally Advanced Adenocarcinoma of the Rectum

SWOG Cancer Research Network

Overview

RATIONALE: Drugs used in chemotherapy, such as irinotecan, leucovorin, fluorouracil, and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well different regimens of induction chemotherapy followed by chemoradiotherapy work in treating patients with locally advanced adenocarcinoma of the rectum.

OBJECTIVES: * Determine the feasibility of obtaining a pre-treatment determination of intratumoral molecular markers (TS, DPD, and ERCC-1) for use in selection of the appropriate regimen for induction cytotoxic combination chemotherapy in patients with cT3-4 rectal adenocarcinoma. * Determine the response probability (unconfirmed, complete and partial) in patients treated with targeted induction cytotoxic chemotherapy. * Determine the toxicity of targeted induction cytotoxic chemotherapy and chemoradiotherapy in these patients. * Determine the response probability in these patients treated with chemoradiotherapy. OUTLINE: This is a multicenter study. * Induction chemotherapy: Patients are assigned to 1 of 3 treatment groups based on molecular analysis of the pretreatment tumor specimen. * Group I (lower likelihood of resistance to a fluorouracil-based regimen): Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. * Group II (higher likelihood of resistance to a fluorouracil-based regimen): Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on day 1. * Group III (high likelihood of sensitivity to oxaliplatin and fluorouracil therapy): Patients receive oxaliplatin IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment in all groups repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are evaluated for response approximately 2 weeks after the completion of induction chemotherapy. Patients with stable disease or better receive chemoradiotherapy. * Chemoradiotherapy: Beginning approximately 3 weeks after the completion of induction chemotherapy, patients receive oral capecitabine twice daily continuously for 5 weeks and concurrent radiotherapy once daily 5 days a week for 5 weeks. After chemoradiotherapy, patients may undergo attempted surgical resection at the discretion of the treating physician. Patients are followed every 3 months for 1 year and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 10-65 patients will be accrued for this study.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

Colorectal Cancer

Interventions

capecitabineDRUG

825mg/m2 BID, PO, daily

fluorouracilDRUG

Bolus + IV for 46 hrs on Day 1

irinotecan hydrochlorideDRUG

IV infusion over 90 min on Day 1

leucovorin calcium

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: * Histologically confirmed primary adenocarcinoma of the rectum * Locally advanced disease (clinical T3-4, N0-2, M0) based on at least 1 of the following criteria: * Clinically fixed tumors on rectal examination with tumor adherent to the pelvic sidewall and/or sacrum * Sciatica attributed to sacral root invasion with CT scan/MRI evidence of the lack of clear tissue plane is considered evidence of fixation * Hydronephrosis on CT scan or intravenous pyelogram of ureteric or bladder invasion by cystoscopy and cytology or biopsy * Invasion into the prostate, vagina, or uterus * Transmural penetration of tumor through the muscularis propria as evidenced by CT scan or MRI and endorectal ultrasound * Distal border of the tumor must be at or below the peritoneal reflection (within 12 cm of the anal verge) by proctoscopic examination * Measurable disease by x-ray, scans, or physical examination * Available tumor tissue to determine molecular profile of the tumor before study treatment * No clinical evidence of high-grade (lumen diameter \< 1 cm) large bowel obstruction unless a diverting colostomy has been performed PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * WBC ≥ 3,500/mm\^3 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥100,000/mm\^3 Hepatic * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * SGOT or SGPT ≤ 2.5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN Renal * See Disease Characteristics * Creatinine ≤ 1.5 times ULN OR * Estimated creatinine clearance \> 50 mL/min Cardiovascular * No significant cardiac disease * No recent myocardial infarction Gastrointestinal * See Disease Characteristics * Able to swallow oral medication * No active inflammatory bowel disease Other * Not pregnant or nursing * Fertile patients must use effective contraception * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No prior unanticipated severe reaction to study drugs * No known dihydropyrimidine dehydrogenase deficiency * No serious uncontrolled infection * No other serious medical illness that would preclude study treatment PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy for colon or rectal cancer Endocrine therapy * Not specified Radiotherapy * No prior pelvic radiotherapy * No prior intra-operative radiotherapy or brachytherapy * No concurrent intra-operative radiotherapy or brachytherapy * No concurrent intensity-modulated radiotherapy Surgery * See Disease Characteristics * See Radiotherapy

Outcomes

Primary Outcomes

Response (confirmed and unconfirmed response, complete response, partial response)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.