Colorectal Cancer
Conditions
Keywords
stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum
Brief summary
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.
Detailed description
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.
Interventions
DRUGcapecitabine
825mg/m2 BID, PO, daily
DRUGfluorouracil
Bolus + IV for 46 hrs on Day 1
DRUGirinotecan hydrochloride
IV infusion over 90 min on Day 1
DRUGleucovorin calcium
200mg/m2 IV 2 hour infusion on Day 1
DRUGoxaliplatin
85mg/m2 IV infusion for 90minutes on Day 1
RADIATIONradiation therapy
Original Planning Target Volume (PTV1): The total dose to the prescription point shall be 4500 cGy in 25 fractions (Monday - Friday inclusive). Boost Planning Target Volume (PTV2): The cumulative dose within the boost volume to the prescription point shall be 5,040 - 5,400 cGy (per Section 7.5b). Daily Dose: The daily dose to the prescription point of the original and boost volumes shall be 180 cGy. Fractionation: Treatment shall be given 5 days/week. All radiation fields shall be treated once daily.
DRUGPyridoxine
50mg TID, PO daily
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response (confirmed and unconfirmed response, complete response, partial response) | — |
Outcome results
None listed