Combination Chemotherapy and Computer-Planned Radiation Therapy in Treating Patients With Unresectable Stage III Non-Small Cell Lung Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Lung Cancer

Treatments: Drug: paclitaxel; Radiation: radiation therapy; Drug: carboplatin; Drug: gemcitabine hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00033553

CALGB-30105

U10CA031946 (U.S. NIH Grant/Contract)

CDR0000069300 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Computer systems that allow doctors to create a 3-dimensional picture of the tumor to plan treatment may result in more effective radiation therapy. It is not yet known which chemotherapy and/or radiation therapy regimen is more effective in treating non-small cell lung cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of different combination chemotherapy regimens and 3-dimensional radiation therapy in treating patients who have unresectable stage III non-small cell lung cancer.

Full description

OBJECTIVES:

• Compare the overall response rate, failure-free survival, and survival of patients with inoperable stage IIIA or IIIB non-small cell lung cancer treated with paclitaxel and carboplatin with concurrent 3-dimensional conformal radiotherapy (3-D XRT) vs gemcitabine and carboplatin with concurrent 3-D XRT.
• Compare the toxicity of these regimens in these patients.
• Compare the pattern of failure (locoregional vs distant failure) in patients treated with these regimens.
• Determine the feasibility of delivering 3-D XRT to patients in this multicenter study.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients then receive paclitaxel IV over 1 hour followed by carboplatin IV over 30 minutes once weekly and 3-dimensional conformal radiotherapy (3-D XRT) once daily 5 days a week. Treatment repeats weekly for 7 courses.
• Arm II: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients then receive gemcitabine IV over 30 minutes twice weekly and 3-D XRT as in arm I. Treatment repeats weekly for 7 courses.

In both arms, treatment continues in the absence of disease progression.

Patients are followed every 2 months for 2 years, every 4 months for 2 years, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 82 patients (41 per treatment arm) will be accrued for this study within 9 months.

Enrollment: 69 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

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

  • Squamous cell carcinoma
  • Adenocarcinoma, including bronchoalveolar cell carcinoma
  • Large cell anaplastic carcinoma, including giant and clear cell carcinoma

• Inoperable stage IIIA or IIIB disease

• No direct invasion of vertebral body

  • Tumors adjacent to a vertebral body without bone invasion allowed if all gross disease can be encompassed in radiotherapy boost field

• Contralateral mediastinal disease (N3) allowed if all gross disease can be encompassed in radiotherapy boost field

• No scalene, supraclavicular, or contralateral hilar node involvement

• Transudate, cytologically negative, non-bloody pleural effusion allowed if it can be encompassed in radiotherapy field

  • No exudative, bloody, or cytologically malignant pleural effusion
  • Evidence of pleural effusion by chest CT scan but not chest x-ray that is too small to tap allowed

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by conventional techniques OR

  • At least 10 mm by spiral CT scan

  • The following are not considered measurable disease:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
    • Tumor lesions in a previously irradiated field

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin less than 1.5 mg/dL
• AST less than 2 times upper limit of normal

Renal:

• Creatinine clearance 20-130 mL/min for females
• Creatinine clearance 20-150 mL/min for males

Pulmonary:

• FEV1 at least 1.2 L

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other currently active malignancy (defined as completed prior therapy and considered to be at less than 30% risk of relapse) except non-melanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for NSCLC
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except steroids for adrenal failure or septic shock, hormones for non-disease-related conditions (e.g., insulin for diabetes), or glucocorticosteroids as antiemetics

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy for NSCLC

Surgery:

• At least 2 weeks since prior exploratory thoracotomy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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69 participants in 2 patient groups

Paclitaxel + Carboplatin

Experimental group

Description:

Paclitaxel and carboplatin induction (2 cycles)followed by chemotherapy with the addition of radiotherapy for 7 cycles

Treatment:

Drug: paclitaxel

Radiation: radiation therapy

Drug: carboplatin

Gemcitabine + Carboplatin

Experimental group

Description:

Gemcitabine and carboplatin induction (2cycles) followed by chemotherapy with the addition of radiotherapy for 7 cycles

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: carboplatin