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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Anal Cancer; Drug/Agent Toxicity by Tissue/Organ; Radiation Enteritis
• Intervention / Treatment: Other: Placebo; Drug: octreotide acetate

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 233
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Foundation for Cancer Research and Education
  • California
    • Chico, California, United States, 95926
      • Enloe Cancer Center at Enloe Medical Center
    • Fresno, California, United States, 93720
      • California Cancer Center - Woodward Park Office
    • Fresno, California, United States, 93720-3397
      • Saint Agnes Medical Center
    • Greenbrae, California, United States, 94904
      • Sutter Health Western Division Cancer Research Group
    • Inglewood, California, United States, 90301
      • Cancer Care Consultants Medical Associates at Daniel Freeman Memorial Hospital
    • Northridge, California, United States, 91328
      • Leavey Cancer Center at Northridge Hospital Medical Center
    • Oakland, California, United States, 94609
      • CCOP - Bay Area Tumor Institute
    • Pomona, California, United States, 91767
      • Pomona Valley Hospital Medical Center
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Incorporated
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Torrance, California, United States, 90509
      • Torrance Memorial Medical Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Memorial Hospital Cancer Center
    • Grand Junction, Colorado, United States, 81502
      • St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
    • Gainesville, Florida, United States, 32610-0232
      • University of Florida Shands Cancer Center
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute at Memorial Regional Hospital
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
    • Jupiter, Florida, United States, 33458
      • Ella Milbank Foshay Cancer Center at Jupiter Medical Center
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center
    • Miami, Florida, United States, 33176
      • Baptist-South Miami Regional Cancer Program
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
    • Tampa, Florida, United States, 33612
      • Veterans Affairs Medical Center - Tampa (Haley)
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B. Amos Community Cancer Center
  • Illinois
    • Harvey, Illinois, United States, 60426
      • Ingalls Cancer Care Center at Ingalls Memorial Hospital
  • Indiana
    • Anderson, Indiana, United States, 46016
      • St. John's Cancer Center at St. John's Medical Center
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Veterans Affairs Medical Center - Indianapolis
    • Muncie, Indiana, United States, 47303-3499
      • Ball Memorial Hospital
  • Iowa
    • Dubuque, Iowa, United States, 52001
      • Wendt Regional Cancer Center at Finley Hospital
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0084
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
    • Lexington, Kentucky, United States, 40503-9985
      • Central Baptist Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
  • Massachusetts
    • Hyannis, Massachusetts, United States, 02601
      • Cape Cod Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Ann Arbor, Michigan, United States, 48106-0995
      • St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Lansing, Michigan, United States, 48909
      • Sparrow Regional Cancer Center
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak Campus
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Springfield, Missouri, United States, 65802
      • CCOP - Cancer Research for the Ozarks
    • Springfield, Missouri, United States, 65804
      • St. John's Regional Health Center
    • St Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center at Methodist Hospital - Omaha
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
    • Reno, Nevada, United States, 89502
      • Washoe Cancer Services at Washoe Medical Center - Reno
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cancer Institute of New Jersey at Cooper University Hospital - Camden
    • Long Branch, New Jersey, United States, 07740-6395
      • Monmouth Medical Center
    • Toms River, New Jersey, United States, 08755
      • Community Regional Cancer Center at Community Medical Center
    • Trenton, New Jersey, United States, 08629
      • Fox Chase Cancer Center at St. Francis Medical Center
    • Vineland, New Jersey, United States, 08360
      • South Jersey Healthcare Regional Cancer Center
  • New York
    • Brooklyn, New York, United States, 11203
      • Suny Downstate Medical Center
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • Brooklyn, New York, United States, 11201
      • Long Island College Hospital
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Manhasset, New York, United States, 11030
      • CCOP - North Shore University Hospital
    • Rochester, New York, United States, 14621
      • Lipson Cancer and Blood Center at Rochester General Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • Trinity Cancer Care Center
  • Ohio
    • Akron, Ohio, United States, 44309-2090
      • Akron City Hospital
    • Canton, Ohio, United States, 44710-1799
      • Aultman Hospital Cancer Center at Aultman Health Foundation
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Lima, Ohio, United States, 45801
      • St. Rita's Medical Center
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Cancer Center at Hillcrest Hospital
    • Salem, Ohio, United States, 44460
      • Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • LaFortune Cancer Center at St. John Medical Center
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Portland, Oregon, United States, 97213-2967
      • Providence Cancer Center at Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
    • Portland, Oregon, United States, 97227
      • Institute of Oncology at Vilnius University
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Regional Cancer Center at Delaware County Memorial Hospital
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • Paoli, Pennsylvania, United States, 19301-1792
      • Paoli Memorial Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center at Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15224-1791
      • Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15219
      • Mercy Cancer Institute at Mercy Hospital
    • Reading, Pennsylvania, United States, 19612-6052
      • Reading Hospital and Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • Texas
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
  • Washington
    • Bellingham, Washington, United States, 98225
      • St. Joseph Hospital Community Cancer Center
    • Vancouver, Washington, United States, 98668
      • Southwest Washington Medical Center Cancer Center
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • Milwaukee, Wisconsin, United States, 53215
      • Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia St. Mary's Cancer Center
    • Racine, Wisconsin, United States, 53405
      • All Saints Cancer Center at All Saints Healthcare
    • West Milwaukee, Wisconsin, United States, 53227
      • West Allis Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sandostatin LAR® Depot; Sandostatin LAR® Depot Pre-RT (between day -7 and day -4 of RT) and Day 22 (± 3 days)	Drug: octreotide acetate
Placebo Comparator: Placebo; Placebo Pre-RT (between day -7 and day -4 of RT) and Day 22 (± 3 days)	Other: Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Babu Zachariah, MD, H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

General Publications

• Zachariah B, Gwede CK, James J, Ajani J, Chin LJ, Donath D, Rosenthal SA, Kane BL, Rotman M, Berk L, Kachnic LA. Octreotide acetate in prevention of chemoradiation-induced diarrhea in anorectal cancer: randomized RTOG trial 0315. J Natl Cancer Inst. 2010 Apr 21;102(8):547-56. doi: 10.1093/jnci/djq063. Epub 2010 Mar 25.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: January 9, 2004
• First Submitted That Met QC Criteria: January 12, 2004
• First Posted (Estimate): January 13, 2004

Study Record Updates

• Last Update Posted (Estimate): November 17, 2015
• Last Update Submitted That Met QC Criteria: November 14, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: recurrent rectal cancer; recurrent anal cancer; drug/agent toxicity by tissue/organ; stage II anal cancer; stage IIIA anal cancer; stage IIIB anal cancer; stage II rectal cancer; stage III rectal cancer; stage I anal cancer; stage I rectal cancer; radiation enteritis
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Neoplasms; Neoplasms by Site; Signs and Symptoms, Digestive; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Anus Diseases; Diarrhea; Rectal Neoplasms; Enteritis; Drug-Related Side Effects and Adverse Reactions; Anus Neoplasms; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: RTOG-0315; CDR0000349441