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

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 3

Conditions: Anal Cancer; Radiation Enteritis; Drug/Agent Toxicity by Tissue/Organ; Colorectal Cancer

Treatments: Drug: octreotide acetate; Other: Placebo

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00075868

RTOG-0315

CDR0000349441

Details and patient eligibility

About

RATIONALE: Octreotide may be effective in preventing or controlling diarrhea in patients who are undergoing chemoradiotherapy for anal or rectal cancer. It is not yet known whether octreotide is effective in treating diarrhea.

PURPOSE: This randomized phase III trial is studying octreotide in preventing or reducing diarrhea in patients who are undergoing chemoradiotherapy for anal or rectal cancer.

Full description

OBJECTIVES:

Primary

• 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

• Compare the quality of life of patients treated with this drug vs placebo.
• 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.
• Compare treatment delays and/or dose reductions (chemotherapy and radiotherapy) in patients treated with these drugs.

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.

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

Enrollment: 233 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary anal or rectal cancer

  • No metastasis beyond the pelvic regional nodes

• Must be scheduled to receive chemoradiotherapy

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

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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233 participants in 2 patient groups, including a placebo group

Sandostatin LAR® Depot

Experimental group

Description:

Sandostatin LAR® Depot Pre-RT (between day -7 and day -4 of RT) and Day 22 (± 3 days)

Treatment:

Drug: octreotide acetate

Placebo

Placebo Comparator group

Description:

Placebo Pre-RT (between day -7 and day -4 of RT) and Day 22 (± 3 days)

Treatment:

Other: Placebo