Clinical trial NCT00046904: Etanercept in Treating Cancer-Related Cachexia and Anorexia in Patients With Advanced Cancer
Official title: Phase III Placebo-Controlled, Randomized, Double-Blind Comparison Of Etanercept (Enbrel) Versus Placebo For The Treatment Of Cancer-Associated Weight Loss And Anorexia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anorexia
Cachexia
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
anorexia
cachexia
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Etanercept is a substance that is being studied as a treatment for cachexia (weight loss) and anorexia (lack of appetite) in patients who have cancer. It is not yet known whether etanercept is effective in improving cancer-related cachexia and anorexia.

PURPOSE: Randomized phase III trial to determine the effectiveness of etanercept in treating cancer-related cachexia and anorexia in patients who have advanced cancer.

Detailed description: OBJECTIVES:

* Compare etanercept vs placebo in the treatment of cancer-related cachexia and anorexia, in terms of weight measurement and rate of weight change, in patients with advanced malignancies.
* Determine the effect of this drug on nausea and vomiting in these patients.
* Assess the functional status and appetite of patients treated with this drug.
* Assess the quality of life of patients treated with this drug.
* Determine the toxic effects of this drug in these patients.
* Determine whether this drug prolongs survival of these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to primary malignant disease (lung vs gastrointestinal vs other), severity of weight loss (less than 4.6 kg vs at least 4.6 kg), planned concurrent chemotherapy (yes vs no), age (less than 50 vs 50 and over), gender, planned use of megestrol or other progestational agent (yes vs no), and GBU Prognostic Index (good vs bad vs unsure). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive etanercept subcutaneously (SC) twice weekly.
* Arm II: Patients receive placebo SC twice weekly. Treatment in both arms continues for a maximum of 24 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, weekly for 1 month, and then monthly during treatment.

Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 274 patients (137 per treatment arm) will be accrued for this study within 19 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed malignancy except brain cancer

  * If the patient has multiple primaries or an unknown primary, the currently active cancer cannot be brain cancer
* Disease considered incurable with available therapies
* No clinical evidence of ascites
* Weight loss of at least 5 pounds (2.3 kg) within the past 2 months (excluding perioperative weight loss) and/or estimated caloric intake of less than 20 cal/kg daily
* Weight gain determined by physician to be beneficial
* Patient perceives weight loss as a problem

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* More than 3 months

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

Cardiovascular

* No poorly controlled congestive heart failure
* No poorly controlled hypertension
* No pacemaker, implanted defibrillator, stents, or metal suture material in the heart or great vessels (for patients participating in the BIA translational portion of the study)

Gastrointestinal

* No known mechanical obstruction of the alimentary tract
* No malabsorption
* No intractable vomiting (more than 5 episodes/week)
* Not concurrently receiving tube feedings or parenteral nutrition

Other

* Able to reliably administer subcutaneous medication twice weekly
* Alert and mentally competent
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

* More than 1 month since prior infliximab
* No concurrent live vaccination

Chemotherapy

* Concurrent chemotherapy allowed

Endocrine therapy

* At least 1 month since prior adrenal steroids
* No concurrent adrenal steroids (inhalant, topical, or optical steroids allowed)

  * Concurrent short-term dexamethasone for chemotherapy-induced emesis is allowed

Radiotherapy

* Concurrent radiotherapy allowed

Surgery

* Not specified

Other

* More than 1 month since prior etanercept
* No concurrent evaluation with another device that injects an electrical current into the body (for patients participating in the bioelectrical impendance analysis \[BIA\] translational portion of the study)

Primary outcomes:
measure: Comparison of weight gain and rate of weight change
Secondary outcomes:
measure: Differences in appetite
measure: Overall survival
measure: Incidence of treatment-related toxicity
measure: Comparison of quality of life (QOL) as assessed by the QOL UNISCALE and the Functional Assessment of Cancer Therapy-Anorexia/cachexia (FACT-An) scale at baseline, weekly for one month, and then monthly during study treatment
Other outcomes:
Locations:
city: Mobile
country: United States
facility: MBCCOP - Gulf Coast
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Honolulu
country: United States
facility: MBCCOP - Hawaii
state: Hawaii
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Bismarck
country: United States
facility: Cancer Care Center at Medcenter One Hospital
state: North Dakota
city: Tulsa
country: United States
facility: CCOP - Oklahoma
state: Oklahoma
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
Study officials:
affiliation: Mayo Clinic
name: Aminah Jatoi, MD
role: STUDY_CHAIR
References:
citation: Jatoi A, Dakhil SR, Nguyen PL, Sloan JA, Kugler JW, Rowland KM Jr, Soori GS, Wender DB, Fitch TR, Novotny PJ, Loprinzi CL. A placebo-controlled double blind trial of etanercept for the cancer anorexia/weight loss syndrome: results from N00C1 from the North Central Cancer Treatment Group. Cancer. 2007 Sep 15;110(6):1396-403. doi: 10.1002/cncr.22944.
citation: Jatoi A, Dakhil SR, Kugler JW, et al.: A placebo-controlled trial of etanercept, a tumor necrosis factor (TNF) inhibitor, in patients with the cancer anorexia/weight loss syndrome. North Central Cancer Treatment Group (NCCTG) trial N00C1. [Abstract] J Clin Oncol 24 (Suppl 18): A-8534, 476s, 2006.