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

NCT00070434 | Withdrawn Phase 2 DMC

• 3 other identifiers: CDR0000334469U10CA032102S0304
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Colorectal Cancer

Keywords

stage II rectal cancer; stage III rectal cancer; adenocarcinoma of the rectum

Outcome Measures

Primary Outcomes (1)

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

Study Arms (3)

Irinotecan + 5-FU + Leucovorin

EXPERIMENTAL

Irinotecan 180mg/m2, IV for 90min on Day 1, q 2 wk x 4 cycles; 5-FU 400 mg/m2, IV bolus on Day 1, q 2 wk x 4 cycles; 5-FU 2.4 g/m2 IV for 46 hours on Day 1, q 2 wk x 4 cycles; Leucovorin 200 mg/m2 IV for 2 hours on Day 1, q 2 wk x4 cycles.

Drug: capecitabine; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium; Radiation: radiation therapy; Drug: Pyridoxine

Irinotecan + Oxaliplatin

EXPERIMENTAL

Irinotecan 175mg/m2 IV for 90 minutes on Day 1, q 2wk x4 cycles; Oxaliplatin 85mg/m2 IV for 2 hours on Day 1, q 2wk x4 cycles

Drug: capecitabine; Drug: irinotecan hydrochloride; Drug: oxaliplatin; Radiation: radiation therapy; Drug: Pyridoxine

Oxaliplatin + 5-FU + Leucovorin

EXPERIMENTAL

Oxaliplatin 85mg/m2 IV for 90 minutes on Day 1, q 2wk x4 cycles; 5-FU 400mg/m2 IV bolus on Day 1, q 2wk x4 cycles; 5-FU 2.4g/m2 IV for 46 hours on Day 1, q 2wk x4 cycles; Leucovorin 200mg/m2 IV for 2 hours on Day 1, q 2wk x4 cycles.

Drug: capecitabine; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Radiation: radiation therapy; Drug: Pyridoxine

Interventions

capecitabine DRUG

825mg/m2 BID, PO, daily

Irinotecan + 5-FU + Leucovorin; Irinotecan + Oxaliplatin; Oxaliplatin + 5-FU + Leucovorin

fluorouracil DRUG

Bolus + IV for 46 hrs on Day 1

Irinotecan + 5-FU + Leucovorin; Oxaliplatin + 5-FU + Leucovorin

irinotecan hydrochloride DRUG

IV infusion over 90 min on Day 1

Irinotecan + 5-FU + Leucovorin; Irinotecan + Oxaliplatin

leucovorin calcium DRUG

200mg/m2 IV 2 hour infusion on Day 1

Irinotecan + 5-FU + Leucovorin; Oxaliplatin + 5-FU + Leucovorin

oxaliplatin DRUG

85mg/m2 IV infusion for 90minutes on Day 1

Irinotecan + Oxaliplatin; Oxaliplatin + 5-FU + Leucovorin

radiation therapy RADIATION

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.

Irinotecan + 5-FU + Leucovorin; Irinotecan + Oxaliplatin; Oxaliplatin + 5-FU + Leucovorin

Pyridoxine DRUG

50mg TID, PO daily

Irinotecan + 5-FU + Leucovorin; Irinotecan + Oxaliplatin; Oxaliplatin + 5-FU + Leucovorin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms

Interventions

Capecitabine; Fluorouracil; Irinotecan; Leucovorin; Oxaliplatin; Radiotherapy; Pyridoxine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Therapeutics; Vitamin B 6; Picolines; Pyridines

Study Officials

• Charles R. Thomas, MD

  The University of Texas Health Science Center at San Antonio

  STUDY CHAIR

• Heinz-Josef Lenz, MD

  University of Southern California

  STUDY CHAIR

• Robert P. Whitehead, MD

  University of Texas

  STUDY CHAIR

• James L. Abbruzzese, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

• Stephen R. Smalley, MD

  Radiation Oncology Center of Olathe

  STUDY CHAIR

• Morton S. Kahlenberg, MD

  The University of Texas Health Science Center at San Antonio

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2003
• First Posted: October 7, 2003
• Study Start: August 1, 2004
• Primary Completion: February 1, 2006
• Last Updated: June 7, 2012

Record last verified: 2012-06