Docetaxel With or Without Infliximab in Treating Weight Loss, Loss of Appetite, and Fatigue in Patients With Unresectable Non-Small Cell Lung Cancer (Infliximab Treatment Discontinued Effective 10/05/05)

Study Overview
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Brief Summary
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RATIONALE: 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. (Infliximab treatment discontinued effective 10/05/05) PURPOSE: 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. (Infliximab treatment discontinued effective 10/05/05)

Detailed Description
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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 (infliximab treatment discontinued effective 10/05/05). 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 (infliximab treatment discontinued effective 10/05/05). 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). Part A (non-randomized, single-center portion of study): Five patients receive infliximab IV (infliximab treatment discontinued effective 10/05/05) 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 [infliximab treatment discontinued effective 10/05/05]) 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. If none of the 5 patients experiences any grade 4 or 5 toxicity directly attributable to infliximab (infliximab treatment discontinued effective 10/05/05), additional patients are accrued for part B of the study. Part B (randomized, multicenter portion of study): Patients are randomized to 1 of 2 treatment arms. Arm I (infliximab treatment discontinued effective 10/05/05): Patients receive infliximab and docetaxel as in part A. Arm II: Patients receive docetaxel as in part A and placebo IV over 2 hours according to the infliximab schedule in part A (infliximab treatment discontinued effective 10/05/05). Treatment in both arms repeats as in part A. 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.

Official Title
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Docetaxel And Infliximab/Placebo In Non-Small Cell Lung Cancer (NSCLC) Patients Greater Than Or Equal To 65 Years Of Age Or In NSCLC Patients With Poor Performance Status: A Double-Blind Randomized, Placebo-Controlled Trial To Prevent And Treat Wasting, Anorexia, And Asthenia In Chemotherapy-Naive And Previously-Treated Patients

Conditions
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Anorexia, Cachexia, Fatigue, Lung Cancer

Intervention / Treatment
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* Biological: infliximab
* Drug: docetaxel
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: infliximab + docetaxel<br>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. 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. | Biological: infliximab<br> <br> Drug: docetaxel<br> <br> |
| Active Comparator: placebo + docetaxel<br>Patients receive docetaxel IV over 1 hour (immediately after completion of infliximab infusion once weekly on weeks 1-6 of each course. Patients receive placebo 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. Treatment repeats every 8 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. 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. | Drug: docetaxel<br> <br> Other: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of weight |  | Up to 5 years | 
| Rate of weight change |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Up to 5 years | 
| Incidence of treatment-related toxicity |  | Up to 5 years | 
| Cancer-related fatigue as measured by the Brief Fatigue Inventory |  | Up to 5 years | 
| Time-to-weight decline |  | Up to 5 years | 
| Appetite |  | Up to 5 years | 
| Lean tissue changes |  | Up to 5 years | 
| Quality of life |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, fatigue, anorexia, cachexia