Clinical trial NCT00075868: Octreotide in Preventing or Reducing Diarrhea in Patients Receiving Chemoradiotherapy for Anal or Rectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anal Cancer
Colorectal Cancer
Drug/Agent Toxicity by Tissue/Organ
Radiation Enteritis
Keywords: radiation enteritis
drug/agent toxicity by tissue/organ
stage I rectal cancer
stage II rectal cancer
stage III rectal cancer
stage IIIA anal cancer
stage IIIB anal cancer
recurrent anal cancer
stage I anal cancer
stage II anal cancer
recurrent rectal cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-01-13
Enrollment: 233
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Prevention of the incidence of moderate, severe, or life-threatening diarrhea
Secondary outcomes:
measure: Quality of life
measure: Economic measures
measure: 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
measure: Prevention of the incidence of severe or life-threatening (i.e., grade 3-5) diarrhea
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Phoenix
country: United States
facility: Foundation for Cancer Research and Education
state: Arizona
city: Chico
country: United States
facility: Enloe Cancer Center at Enloe Medical Center
state: California
city: Fresno
country: United States
facility: Saint Agnes Medical Center
state: California
city: Fresno
country: United States
facility: California Cancer Center - Woodward Park Office
state: California
city: Greenbrae
country: United States
facility: Sutter Health Western Division Cancer Research Group
state: California
city: Inglewood
country: United States
facility: Cancer Care Consultants Medical Associates at Daniel Freeman Memorial Hospital
state: California
city: Northridge
country: United States
facility: Leavey Cancer Center at Northridge Hospital Medical Center
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Pomona
country: United States
facility: Pomona Valley Hospital Medical Center
state: California
city: Sacramento
country: United States
facility: Radiological Associates of Sacramento Medical Group, Incorporated
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Torrance
country: United States
facility: Torrance Memorial Medical Center
state: California
city: Colorado Springs
country: United States
facility: Memorial Hospital Cancer Center
state: Colorado
city: Grand Junction
country: United States
facility: St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
state: Colorado
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
state: Florida
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: Florida
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Jupiter
country: United States
facility: Ella Milbank Foshay Cancer Center at Jupiter Medical Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: Baptist-South Miami Regional Cancer Program
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
city: Tampa
country: United States
facility: Veterans Affairs Medical Center - Tampa (Haley)
state: Florida
city: Columbus
country: United States
facility: John B. Amos Community Cancer Center
state: Georgia
city: Harvey
country: United States
facility: Ingalls Cancer Care Center at Ingalls Memorial Hospital
state: Illinois
city: Anderson
country: United States
facility: St. John's Cancer Center at St. John's Medical Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis
state: Indiana
city: Muncie
country: United States
facility: Ball Memorial Hospital
state: Indiana
city: Dubuque
country: United States
facility: Wendt Regional Cancer Center at Finley Hospital
state: Iowa
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Hyannis
country: United States
facility: Cape Cod Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Pascagoula
country: United States
facility: Regional Cancer Center at Singing River Hospital
state: Mississippi
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: St Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: Methodist Cancer Center at Methodist Hospital - Omaha
state: Nebraska
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: CCOP - Nevada Cancer Research Foundation
state: Nevada
city: Reno
country: United States
facility: Washoe Cancer Services at Washoe Medical Center - Reno
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cancer Institute of New Jersey at Cooper University Hospital - Camden
state: New Jersey
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Toms River
country: United States
facility: Community Regional Cancer Center at Community Medical Center
state: New Jersey
city: Trenton
country: United States
facility: Fox Chase Cancer Center at St. Francis Medical Center
state: New Jersey
city: Vineland
country: United States
facility: South Jersey Healthcare Regional Cancer Center
state: New Jersey
city: Brooklyn
country: United States
facility: Long Island College Hospital
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Rochester
country: United States
facility: Lipson Cancer and Blood Center at Rochester General Hospital
state: New York
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Statesville
country: United States
facility: Iredell Memorial Hospital
state: North Carolina
city: Minot
country: United States
facility: Trinity Cancer Care Center
state: North Dakota
city: Akron
country: United States
facility: Akron City Hospital
state: Ohio
city: Canton
country: United States
facility: Aultman Hospital Cancer Center at Aultman Health Foundation
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Lima
country: United States
facility: St. Rita's Medical Center
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Cancer Center at Hillcrest Hospital
state: Ohio
city: Salem
country: United States
facility: Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Tulsa
country: United States
facility: LaFortune Cancer Center at St. John Medical Center
state: Oklahoma
city: Gresham
country: United States
facility: Legacy Mount Hood Medical Center
state: Oregon
city: Milwaukie
country: United States
facility: Providence Milwaukie Hospital
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Institute of Oncology at Vilnius University
state: Oregon
city: Tualatin
country: United States
facility: Legacy Meridian Park Hospital
state: Oregon
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Drexel Hill
country: United States
facility: Delaware County Regional Cancer Center at Delaware County Memorial Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Paoli
country: United States
facility: Paoli Memorial Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center at Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Mercy Cancer Institute at Mercy Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
city: Reading
country: United States
facility: Reading Hospital and Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists at UCS Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Bellingham
country: United States
facility: St. Joseph Hospital Community Cancer Center
state: Washington
city: Vancouver
country: United States
facility: Southwest Washington Medical Center Cancer Center
state: Washington
city: Yakima
country: United States
facility: North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
state: Washington
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Columbia St. Mary's Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
state: Wisconsin
city: Racine
country: United States
facility: All Saints Cancer Center at All Saints Healthcare
state: Wisconsin
city: West Milwaukee
country: United States
facility: West Allis Memorial Hospital
state: Wisconsin
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Babu Zachariah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Jaffer A. Ajani, MD
role: STUDY_CHAIR
References:
citation: 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.
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 anal or rectal cancer. [Abstract] J Clin Oncol 25 (Suppl 18): A-4032, 2007.