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

Alternate Title

Octreotide in Preventing or Reducing Diarrhea in Patients Receiving Chemoradiotherapy for Anal or Rectal Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Supportive care	Closed	18 and over	NCI	RTOG-0315 NCT00075868

Objectives

Primary

1. Determine the ability of octreotide to prevent the incidence of moderate, severe, or life-threatening chemoradiotherapy-induced diarrhea (grades 2-4) in patients with anal or rectal cancer.

Secondary

1. Compare the quality of life of patients treated with this drug vs placebo.
2. Compare the number of hospitalizations and use of antidiarrheal agents (e.g., Imodium®) related to diarrhea (or its complications) in patients treated with these drugs.
3. Compare treatment delays and/or dose reductions (chemotherapy and radiotherapy) in patients treated with these drugs.

Entry Criteria

Disease Characteristics:

• Histologically confirmed primary anal or rectal cancer
  • No metastasis beyond the pelvic regional nodes



• Must be scheduled to receive chemoradiotherapy

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• Prior chemotherapy allowed

Endocrine therapy

• At least 6 months since prior administration of any of the following:
  • Glucocorticoid therapy
  • Insulin sensitizers (e.g., metformin, pioglitazone, or rosiglitazone)
  • Exogenous growth hormone therapy

Radiotherapy

• See Disease Characteristics
• No prior pelvic radiotherapy
• No prior intensity-modulated radiotherapy
• No concurrent radiotherapy for abdominal cancer
• No concurrent hyperfractionated, split-course, or intensity-modulated radiotherapy
• No brachytherapy prior to or after completion of all external beam radiotherapy

Surgery

• No prior abdominal-perineal resection or other surgical procedure leaving the patient without a functioning rectum
• No colostomy

Other

• More than 30 days since other prior investigational drugs
• No prior octreotide for cancer therapy-related diarrhea
• No concurrent prophylactic antidiarrheal medication

Patient Characteristics:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Liver function tests < 3 times upper limit of normal
• No prior hepatic disease

Renal

• Not specified

Gastrointestinal

• No prior chronic or acute regional enteritis
• No malabsorption syndrome
• No prior inflammatory bowel disease that may exacerbate the radiotherapy toxicity
• No grade 2 or greater uncontrollable diarrhea at baseline
• No prior cholecystitis or gallstones, unless a cholecystectomy has been performed
• No prior incontinence of stool

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No uncontrolled diabetes (e.g., fasting glucose > 250 mg/dL)
• No prior allergy or hypersensitivity to study drug or other related drug or compound
• No other medical condition or mental impairment that would preclude study treatment and compliance

Expected Enrollment

A total of 226 patients (113 per treatment arm) will be accrued for this study within 2 years.

Outcomes

Prevention of the incidence of moderate, severe, or life-threatening diarrhea

Quality of life
Economic measures
Validity of the Functional Alterations due to Changes in Elimination-Changes in Bowel Function, the Quality of Life-Radiation Therapy Instrument, and the Expand Prostate Index Composite-Bowel questionnaires
Prevention of the incidence of severe or life-threatening (i.e., grade 3-5) diarrhea

Outline

This is a double-blind, placebo-controlled, randomized, multicenter study. Patients are stratified according to radiotherapy dose (< 50 Gy vs ≥ 50 Gy), chemotherapy dose (bolus vs continuous), and gender. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive octreotide* intramuscularly (IM) 4-7 days before the start of chemoradiotherapy and on day 22 (± 3 days) during chemoradiotherapy.



• Arm II: Patients receive placebo* IM 4-7 days before the start of chemoradiotherapy and on day 22 (± 3 days) during chemoradiotherapy.

 [Note: *Patients receive a total of 2 injections of octreotide or placebo]

In both arms, treatment continues in the absence of unacceptable toxicity.

Quality of life is assessed at baseline, at the completion of chemoradiotherapy, and at 3, 6, 9, and 15 months from the start of chemoradiotherapy.

Patients are followed at 3, 6, 9, and 15 months from the start of chemoradiotherapy.

Zachariah B, James J, Gwede CK, et al.: RTOG 0315: a randomized, double-blind, placebo-controlled phase III study to determine the efficacy of octreotide acetate in preventing or reducing the severity of chemoradiation-induced diarrhea in patients with anal or rectal cancer. [Abstract] J Clin Oncol 25 (Suppl 18): A-4032, 2007.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Babu Zachariah, MD, Protocol chair		Ph: 813-972-7667
Jaffer Ajani, MD, Protocol co-chair		Ph: 713-792-2828; 800-392-1611 Email: jajani@mdanderson.org

Registry Information
Official Title		A Randomized, Double Blind, Placebo-Controlled Phase III Study To Determine The Efficacy Of Sandostatin LAR® Depot (Octreotide Acetate) In Preventing Or Reducing The Severity Of Chemoradiation-Induced Diarrhea In Patients With Anal Or Rectal Cancer
Trial Start Date		2003-12-10
Registered in ClinicalTrials.gov		NCT00075868
Date Submitted to PDQ		2003-12-09
Information Last Verified		2006-02-27