Octreotide in Preventing Diarrhea in Patients Who Are Undergoing Radiation Therapy to the Pelvis

Study Overview
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Brief Summary
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RATIONALE: Octreotide may be effective in preventing or controlling diarrhea in patients who are undergoing radiation therapy to the pelvis. It is not yet known whether octreotide is effective for diarrhea. PURPOSE: Randomized phase III trial to determine the effectiveness of octreotide in preventing diarrhea in patients who are undergoing radiation therapy to the pelvis.

Detailed Description
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OBJECTIVES: Determine the effectiveness of octreotide in reducing acute treatment-related diarrhea in patients receiving external-beam radiotherapy to the pelvis. Determine the effectiveness of this drug in reducing chronic treatment-related bowel dysfunction in these patients. Determine the toxicity of this drug in these patients. Assess the importance that these patients attach to various measures of bowel function. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to prior anterior resection of the rectum (yes vs no), total planned cumulative dose of radiotherapy, including boost fields (4,500-5,350 cGy vs 5,351-6,000 cGy vs more than 6,000 cGy), use of concurrent fluorouracil (none vs bolus vs continuous infusion), use of concurrent leucovorin calcium (yes vs no), use of concurrent cisplatin (yes vs no), superior border of initial field (at or inferior to the L4-5 interspace vs superior to the L4-5 interspace), planned intracavitary brachytherapy (yes vs no), and primary site of disease (rectal cancer vs prostate cancer vs gynecological cancer vs other). Beginning no later than the fourth day of radiotherapy, patients are randomized to one of two treatment arms. Arm I: Patients receive short-acting octreotide subcutaneously (SC) on day 1 and long-acting octreotide intramuscularly (IM) on days 2 and 29. Arm II: Patients receive placebo SC on day 1 and IM on days 2 and 29. In both arms, treatment continues in the absence of unacceptable toxicity or the development of severe diarrhea. Patients complete a bowel function questionnaire at baseline, weekly during radiotherapy, and then weekly for 4 weeks and at 1 and 2 years after completion of radiotherapy. Patients are followed weekly for 4 weeks and then at 1 and 2 years.

Official Title
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Phase III Double-Blind Study Of Depot Octreotide Versus Placebo In The Prevention Of Acute Diarrhea In Patients Receiving Pelvic Radiation Therapy

Conditions
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Cervical Cancer, Colorectal Cancer, Diarrhea, Endometrial Cancer, Fallopian Tube Cancer, Ovarian Cancer, Prostate Cancer, Sarcoma, Unspecified Adult Solid Tumor, Protocol Specific, Vaginal Cancer, Vulvar Cancer

Intervention / Treatment
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* Drug: octreotide acetate
* Other: placebo
* Radiation: radiation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed cancer in the pelvis Plan to receive continuous definitive or adjuvant external-beam radiotherapy to the pelvis or pelvis and para-aortic lymph nodes (total planned dose of 4,500-5,350 cGy) Entire pelvis must be encompassed by planned radiotherapy field (superior border not inferior to the most inferior aspect of sacroiliac joints) Portions of rectum may have special blocking depending on disease site Planned treatment for once-daily radiotherapy 4-5 times a week (planned daily dose 170-210 cGy) No planned split-course radiotherapy No planned interstitial brachytherapy prior to completion of external-beam radiotherapy Planned intracavitary radiotherapy allowed No planned cytotoxic chemotherapy agents concurrently with radiotherapy except fluorouracil with or without leucovorin calcium or cisplatin Entered on study before the third radiotherapy fraction No current or prior metastases beyond pelvic or para-aortic lymph nodes No grade 3 or greater diarrhea, rectal bleeding, or abdominal cramping prior to radiotherapy No incontinence of stool PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Renal: No chronic renal failure Creatinine less than 2 times upper limit of normal (for patients with history of renal disease) Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known allergy to octreotide No history of inflammatory bowel disease No other concurrent medical condition that would preclude study participation No history of cholecystitis unless prior cholecystectomy PRIOR CONCURRENT THERAPY: Radiotherapy: See Disease Characteristics No prior radiotherapy to the pelvis Surgery: See Disease Characteristics No prior abdominal-perineal resection, Hartmann procedure, or other surgical procedure resulting in non-functioning rectum

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: octreotide + radiation<br>Patients receive short-acting octreotide subcutaneously (SC) on day 1 and long-acting octreotide intramuscularly (IM) on days 2 and 29. Treatment continues in the absence of unacceptable toxicity or the development of severe diarrhea. Patients complete a bowel function questionnaire at baseline, weekly during radiotherapy, and then weekly for 4 weeks and at 1 and 2 years after completion of radiotherapy. Patients are followed weekly for 4 weeks and then at 1 and 2 years. | Drug: octreotide acetate<br> <br> Radiation: radiation<br> <br> |
| Active Comparator: placebo + radiation<br>Patients receive placebo SC on day 1 and IM on days 2 and 29. Treatment continues in the absence of unacceptable toxicity or the development of severe diarrhea. Patients complete a bowel function questionnaire at baseline, weekly during radiotherapy, and then weekly for 4 weeks and at 1 and 2 years after completion of radiotherapy. Patients are followed weekly for 4 weeks and then at 1 and 2 years. | Other: placebo<br> <br> Radiation: radiation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of diarrhea as measured by NCI CTC version 2.0 weekly during pelvic radiotherapy |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of patient-reported bowel dysfunction as assessed by the bowel function questionnaire weekly during radiotherapy, weekly for 4 weeks after radiotherapy, and 12 and 24 months after completion of radiotherapy |  | Up to 2 years | 
| Toxicity as assessed by NCI CTC version 2.0 weekly during pelvic radiotherapy |  | Up to 2 years | 
| Importance that patients attach to various measures of bowel dysfunction as assessed by questionnaire at week 4 of radiotherapy and at 12 and 24 months after completion of radiotherapy |  | Up to 2 years |