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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00075868
• Other study ID #: RTOG-0315
• Secondary ID: CDR0000349441
• Status: Completed
• Phase: Phase 3
• First received: January 9, 2004
• Last updated: November 14, 2015
• Start date: December 2003

Study information

• Verified date: November 2015
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 233
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Anal Cancer
• Anus Neoplasms
• Colorectal Cancer
• Drug/Agent Toxicity by Tissue/Organ
• Enteritis
• Radiation Enteritis

Intervention

Drug:
• octreotide acetate

Other:
• Placebo

Locations

Country	Name	City	State
United States	Akron City Hospital	Akron	Ohio
United States	St. John's Cancer Center at St. John's Medical Center	Anderson	Indiana
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	St. Joseph Hospital Community Cancer Center	Bellingham	Washington
United States	Long Island College Hospital	Brooklyn	New York
United States	New York Methodist Hospital	Brooklyn	New York
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Cancer Institute of New Jersey at Cooper University Hospital - Camden	Camden	New Jersey
United States	Aultman Hospital Cancer Center at Aultman Health Foundation	Canton	Ohio
United States	Enloe Cancer Center at Enloe Medical Center	Chico	California
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Memorial Hospital Cancer Center	Colorado Springs	Colorado
United States	CCOP - Columbus	Columbus	Ohio
United States	John B. Amos Community Cancer Center	Columbus	Georgia
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	Wendt Regional Cancer Center at Finley Hospital	Dubuque	Iowa
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	California Cancer Center - Woodward Park Office	Fresno	California
United States	Saint Agnes Medical Center	Fresno	California
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	CCOP - Greenville	Greenville	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	Cape Cod Hospital	Hyannis	Massachusetts
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Veterans Affairs Medical Center - Indianapolis	Indianapolis	Indiana
United States	Cancer Care Consultants Medical Associates at Daniel Freeman Memorial Hospital	Inglewood	California
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Central Baptist Hospital	Lexington	Kentucky
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	St. Rita's Medical Center	Lima	Ohio
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio
United States	Baptist-South Miami Regional Cancer Program	Miami	Florida
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Columbia St. Mary's Cancer Center	Milwaukee	Wisconsin
United States	Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Trinity Cancer Care Center	Minot	North Dakota
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Ball Memorial Hospital	Muncie	Indiana
United States	Leavey Cancer Center at Northridge Hospital Medical Center	Northridge	California
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Methodist Cancer Center at Methodist Hospital - Omaha	Omaha	Nebraska
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Foundation for Cancer Research and Education	Phoenix	Arizona
United States	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Mercy Cancer Institute at Mercy Hospital	Pittsburgh	Pennsylvania
United States	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Pomona Valley Hospital Medical Center	Pomona	California
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Institute of Oncology at Vilnius University	Portland	Oregon
United States	Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	All Saints Cancer Center at All Saints Healthcare	Racine	Wisconsin
United States	Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Washoe Cancer Services at Washoe Medical Center - Reno	Reno	Nevada
United States	Lipson Cancer and Blood Center at Rochester General Hospital	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital	St Louis	Missouri
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Community Regional Cancer Center at Community Medical Center	Toms River	New Jersey
United States	Torrance Memorial Medical Center	Torrance	California
United States	Fox Chase Cancer Center at St. Francis Medical Center	Trenton	New Jersey
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	LaFortune Cancer Center at St. John Medical Center	Tulsa	Oklahoma
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	South Jersey Healthcare Regional Cancer Center	Vineland	New Jersey
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	West Allis Memorial Hospital	West Milwaukee	Wisconsin
United States	Cancer Treatment Center	Wooster	Ohio
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 — View Citation

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 an

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevention of the incidence of moderate, severe, or life-threatening diarrhea
Secondary	Quality of life
Secondary	Economic measures
Secondary	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
Secondary	Prevention of the incidence of severe or life-threatening (i.e., grade 3-5) diarrhea