Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Induction Chemotherapy Followed By Chemoradiotherapy in Treating Patients With Locally Advanced Adenocarcinoma of the Rectum

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI SWOG-S0304 NCT00070434, S0304

Objectives

1. 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.
2. Determine the response probability (unconfirmed, complete and partial) in patients treated with targeted induction cytotoxic chemotherapy.
3. Determine the toxicity of targeted induction cytotoxic chemotherapy and chemoradiotherapy in these patients.
4. Determine the response probability in these patients treated with chemoradiotherapy.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,500/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥100,000/mm³

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

Expected Enrollment

A total of 10-65 patients will be accrued for this study.

Outcomes

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

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.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Charles Thomas, MD, Study coordinator(Contact information may not be current)		Ph: 210-567-4777 Email: thomasch@ohsu.edu
Heinz-Josef Lenz, MD, Study coordinator		Ph: 323-865-3955; 800-865-0102 Email: lenz_h@ccnt.usc.edu
Robert Whitehead, MD, Study coordinator(Contact information may not be current)		Ph: 409-772-2981
James Abbruzzese, MD, Study coordinator		Ph: 713-792-2828; 800-392-1611
Stephen Smalley, MD, Study coordinator		Ph: 913-768-7200 Email: s_smalley@msn.com
Morton Kahlenberg, MD, Study coordinator		Ph: 210-567-5750 Email: kahlenberg@uthscsa.edu

Registry Information
Official Title		A Phase II Feasibility Translational Research Trial of Induction Chemotherapy Followed by Concomitant Chemoradiation in Patients with Clinical T4 Rectal Cancer
Trial Start Date		2004-08-01
Registered in ClinicalTrials.gov		NCT00070434
Date Submitted to PDQ		2003-09-03
Information Last Verified		2006-01-25
NCI Grant/Contract Number		U10-CA32102

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