RATIONALE:

PURPOSE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Infliximab may improve cancer-related weight loss, lack of appetite, and fatigue. It is not yet known whether docetaxel is more effective with or without infliximab in preventing weight loss and fatigue in patients with advanced cancer.Randomized phase III trial to determine the effectiveness of docetaxel with or without infliximab in preventing weight loss, loss of appetite, and fatigue in patients who have unresectable non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
Anorexia Cachexia Fatigue Non-small cell lung cancer	Drug: docetaxel  Drug: infliximab  Procedure: anticachectic therapy  Procedure: chemotherapy  Procedure: fatigue assessment/management  Procedure: nutritional support  Procedure: supportive care/therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the improvement or stabilization of weight in elderly or poor performance status patients with unresectable non-small cell lung cancer treated with docetaxel with or without infliximab.
• Compare appetite and functional status in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the augmentation or maintenance of lean tissue in patients treated with these regimens.
• Compare the response rates and time to disease progression in patients treated with these regimens.
• Compare the survival of patients treated with these regimens.
• Determine whether the tumor necrosis factor-alpha polymorphisms in the -308 and -238 regions predict which cancer patients will experience loss of appetite and weight and which patients might potentially benefit from infliximab.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to weight loss within the past 6 months (0% vs more than 0% to less than 5% vs at least 5%), number of prior chemotherapy regimens (0 vs 1 vs more than 1), gender, and GBU prognostic index (good vs bad vs unsure).

• Five patients receive infliximab IV over 2 hours once weekly on weeks 1, 3, and 5 of the first course and once weekly on weeks 1 and 5 of all subsequent courses and docetaxel IV over 1 hour (immediately after completion of infliximab infusion) once weekly on weeks 1-6 of each course. Treatment repeats every 8 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients may continue infliximab (even if docetaxel is discontinued or other chemotherapy is initiated) as long as beneficial effects are observed. If none of the 5 patients experiences any grade 4 or 5 toxicity directly attributable to infliximab, additional patients are accrued for part B of the study.
• Patients are randomized to 1 of 2 treatment arms.
• Arm I: Patients receive infliximab and docetaxel as in part A.
• Patients receive docetaxel as in part A and placebo IV over 2 hours according to the infliximab schedule in part A. Treatment in both arms repeats as in part A. Patients may continue infliximab/placebo (even if docetaxel is discontinued or other chemotherapy is initiated) as long as beneficial effects are observed.

Quality of life, fatigue, appetite/anorexia, cachexia, and weight are assessed at baseline, weekly on weeks 1-8, and then monthly for the remainder of study treatment.

Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 220 patients (110 per treatment arm) will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed unresectable non-small cell lung cancer that is considered incurable with other therapies
• Chemotherapy naive or previously treated disease
• Meets one of the following criteria:
• Age 65 and over with ECOG performance status of 0-2
• Under age 65 with ECOG performance status of 2
• No symptomatic or known untreated brain metastases

PATIENT CHARACTERISTICS: Age:

• See Disease Characteristics
• Adult

Performance status:

• See Disease Characteristics
• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic:

• Bilirubin normal
• AST and/or ALT ≤ 2.5 times upper limit of normal (ULN) if alkaline phosphatase less than ULN OR
• Alkaline phosphatase ≤ 4 times ULN if ALT less than ULN
• No ascites

Renal:

• Creatinine ≤ 1.5 times ULN

Cardiovascular:

• No prior or concurrent congestive heart failure

Pulmonary:

• No prior tuberculosis or positive purified protein derivative skin test (tuberculin test)

Other:

• No prior anaphylactic reaction to any taxane
• No known mechanical obstruction of the alimentary tract, malabsorption, or intractable vomiting (more than 5 episodes per week)
• No infection or chronic debilitating illness that would increase the risk of chemotherapy administration
• No grade 2 or greater peripheral neuropathy of any etiology
• No edema
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer
• Alert and mentally competent
• Able to complete questionnaires alone or with assistance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No prior docetaxel for metastatic non-small cell lung cancer

Endocrine therapy:

• At least 1 month since prior adrenal steroids, androgens, progestational agents, or appetite stimulants
• No concurrent adrenal steroids, androgens, progestational agents, or appetite stimulants unless needed (e.g., steroids for CNS metastases)
• Concurrent inhaled, topical, or optical steroids allowed
• Concurrent short-term dexamethasone around days of chemotherapy administration allowed for protection against anaphylaxis and emesis

Radiotherapy:

• More than 3 weeks since prior radiotherapy
• No prior radiotherapy to more than 25% of bone marrow

Surgery:

• More than 3 weeks since prior major surgery

Other:

• More than 3 weeks since other prior antineoplastic therapy

Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States; Recruiting
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States; Recruiting
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States; Recruiting
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States; Recruiting
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
      Coborn Cancer Center, Saint Cloud,  Minnesota,  56303,  United States; Recruiting
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States; Recruiting
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States; Recruiting
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States; Recruiting
Ohio
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States; Recruiting
Pennsylvania
      Allegheny General Hospital, Pittsburgh,  Pennsylvania,  15212-4772,  United States; Recruiting
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States; Recruiting
South Carolina
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States; Recruiting
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States; Recruiting
Wisconsin
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States; Recruiting

Study chairs or principal investigators

Aminah Jatoi, MD,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000069417; NCCTG-N01C9; NCI-P02-0226; NCT00040885
Record last reviewed:  September 2004
Last Updated:  April 4, 2005
Record first received:  July 8, 2002
ClinicalTrials.gov Identifier:  NCT00040885
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08