Gefitinib With or Without Carboplatin and Paclitaxel in Treating Older Patients With Unresectable or Metastatic Non-Small Cell Lung Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Lung Cancer

Treatments: Drug: gefitinib; Drug: carboplatin; Drug: paclitaxel

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00062062

CDR0000304453 (Registry Identifier)

NCCTG-N0222

NCI-2012-02535 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Biological therapies such as gefitinib may interfere with the growth of cancer cells and slow the growth of the tumor. Drugs used in chemotherapy such as carboplatin and paclitaxel use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib with carboplatin and paclitaxel may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gefitinib alone or together with carboplatin and paclitaxel works in treating older patients with unresectable or metastatic non-small cell lung cancer.

Full description

OBJECTIVES:

Primary

• Determine the 6-month progression status of older patients with unresectable or metastatic non-small cell lung cancer treated with gefitinib alone or with carboplatin and paclitaxel.

Secondary

• Determine the response rate in patients treated with these regimens.
• Determine the quality of life of patients treated with these regimens.
• Determine whether serum-secreted or soluble epidermal growth factor receptor (EGFR) concentrations predict response in patients treated with these regimens.
• Correlate the presence of social support for these patients with toxicity and efficacy of these regimens.
• Determine whether social support for these patients differs according to gender.
• Determine the reasons an oncologist would choose a chemotherapy vs a nonchemotherapy regimen for these patients.

Tertiary

• Correlate EGFR signaling pathway markers, RNA expression profile, gene polymorphisms of prespecified germline and tumor genes, and plasma and urine proteomic patterns with response rate and time to progression of patients receiving treatment in group I.

OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 2 treatment groups as determined by their treating physician.

• Group I: Patients receive oral gefitinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Group II: Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of chemotherapy and in the absence of disease progression, patients receive oral gefitinib as in group I.

Quality of life is assessed at baseline and after the completion of course 2.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 107 patients (51 for group I and 56 for group II) will be accrued for this study within 1.7 years.

Enrollment: 65 patients

Sex: All

Ages: 65 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

  • Metastatic or unresectable disease

• Measurable disease

  • At least 1 lesion at least 2.0 cm
  • Disease must be completely outside prior radiotherapy port OR documented disease progression since the completion of radiotherapy

• No meningeal carcinomatosis

• No untreated brain metastases

  • Current metastatic CNS disease must have been treated and clinically stable for at least 2 weeks prior to study chemotherapy

• No potentially curative treatment options available (e.g., chemotherapy with surgery or radiotherapy)

PATIENT CHARACTERISTICS:

Age

• 65 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10.0 g/dL

Hepatic

• Bilirubin no greater than 2.0 mg/dL
• No uncontrolled hepatic disease

Renal

• Creatinine no greater than 2 times upper limit of normal
• No uncontrolled renal disease

Cardiovascular

• No uncontrolled cardiac disease

Pulmonary

• No clinically active interstitial lung disease

  • Asymptomatic, chronic stable radiographic changes allowed

• No uncontrolled respiratory disease

Other

• Fertile patients must use effective contraception
• Able and willing to complete questionnaires alone or with assistance
• No known hypersensitivity to gefitinib or any of its excipients
• No active infection within the past 2 weeks
• No other prior malignancy within the past 5 years except basal cell skin cancer
• No grade 2 or greater peripheral neuropathy (CTC v2.0)
• No uncontrolled diabetes mellitus (for patients receiving study chemotherapy)
• No dysphagia or inability to swallow intact capsules
• No significant medical condition that would preclude study treatment or follow-up
• No severe or uncontrolled systemic disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior chemotherapy for metastatic NSCLC

Endocrine therapy

• Concurrent steroids allowed provided the dose is not changed

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered
• No prior radiotherapy to more than 25% of marrow-containing skeleton
• No concurrent radiotherapy (including palliative)

Surgery

• See Disease Characteristics
• At least 3 weeks since prior major surgery
• No surgery within 7 days after study participation

Other

• More than 30 days since prior non-FDA approved investigational drugs

• No concurrent oral retinoids

• No concurrent CYP3A4-inducing agents, including the following:

  • Carbamazepine
  • Oxcarbazepine
  • Modafinil
  • Ethosuximide
  • Griseofulvin
  • Nafcillin
  • Phenobarbital
  • Phenylbutazone
  • Phenytoin
  • Primidone
  • Rifampin
  • Hypericum perforatum (St. John's wort)
  • Barbiturates
  • Sulfinpyrazone

• No concurrent drugs that cause sustained elevation of gastric pH (≥ 5)

• No concurrent antacids within 4 hours before, during, and within 4 hours after gefitinib administration

• No concurrent itraconazole, fluconazole, ketoconazole, or erythromycin

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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65 participants in 2 patient groups

gefitinib

Experimental group

Description:

Patients receive oral gefitinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and after the completion of course 2. Patients are followed every 3 months for 5 years.

Treatment:

Drug: gefitinib

paclitaxel + carboplatin + gefitinib

Experimental group

Description:

Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of chemotherapy and in the absence of disease progression, patients receive oral gefitinib as in group I. Quality of life is assessed at baseline and after the completion of course 2. Patients are followed every 3 months for 5 years.

Treatment:

Drug: paclitaxel

Drug: gefitinib

Drug: carboplatin