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)

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Anorexia; Lung Cancer; Cachexia; Fatigue

Treatments: Drug: docetaxel; Other: placebo; Biological: infliximab

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00040885

NCI-P02-0226

CDR0000069417 (Registry Identifier)

NCI-2012-02472 (Registry Identifier)

NCCTG-N01C9

Details and patient eligibility

About

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)

Full description

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.

Enrollment: 67 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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67 participants in 2 patient groups

infliximab + docetaxel

Experimental group

Description:

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.

Treatment:

Biological: infliximab

Drug: docetaxel

placebo + docetaxel

Active Comparator group

Description:

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.

Treatment:

Drug: docetaxel

Other: placebo