Gemcitabine, Carboplatin or Paclitaxel Plus Radiation Therapy in Treating Patients With Stage IIIA or IIIB Non-Small Cell Lung Cancer

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 1

Conditions: Lung Cancer

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

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00016315

RTOG-L-0017

RTOG-0017

CDR0000068622

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, carboplatin, and paclitaxel, work in 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. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining combination chemotherapy with radiation therapy in treating patients who have stage IIIA or stage IIIB non-small cell lung cancer.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose (MTD) of gemcitabine when administered with carboplatin and thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in patients with stage IIIA or IIIB non-small cell lung cancer.
• Determine the MTD of gemcitabine and paclitaxel when administered with thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in these patients.

OUTLINE: This is a multicenter, dose-escalation study of gemcitabine and paclitaxel. Patients are sequentially assigned to 1 of 3 treatment regimens.

• Regimen A: Patients receive gemcitabine IV over 30-60 minutes on days 1, 8, 22, 29, and 43 and thoracic radiotherapy daily 5 days a week for 7 weeks beginning on day 1.
• Regimen B (closed to accrual as of 5/13/03): Patients receive gemcitabine and thoracic radiotherapy as in regimen A and carboplatin IV over 30 minutes on days 1, 8, 22, 29, and 43.
• Regimen C: Patients receive gemcitabine and thoracic radiotherapy as in regimen A and paclitaxel IV over 1 hour on days 1, 8, 22, 29, and 43.

At 3 weeks after completion of chemoradiotherapy, all patients receive adjuvant gemcitabine IV over 30-60 minutes on days 71, 78, 92, and 99 and carboplatin IV over 30 minutes on days 71 and 92.

The first 6 patients enrolled receive regimen A to determine the safety of the initial dose of gemcitabine. After completion of regimen A, cohorts of 3-6 patients receive escalating doses of gemcitabine in regimen B (closed to accrual as of 5/13/03) until the maximum tolerated dose (MTD) is determined. In a separate sequence, cohorts of 3-6 patients receive alternating escalating doses of gemcitabine and paclitaxel in regimen C until the MTD is determined. The MTD is defined as the dose preceding that at which at least 3 of 6 patients experience dose-limiting toxicity.

Patients are followed at 3 months, 6 months, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 78 patients will be accrued for this study within 29 months.

Enrollment: 35 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed loco-regionally advanced non-small cell lung cancer meeting one of the following staging criteria:

  • Medically inoperable stage IIIA
  • Unresectable stage IIIA or IIIB

• Measurable disease on three-dimensional planning CT scan

• No post-resection intrathoracic tumor recurrence

• No pleural effusion on chest x-ray except those occurring after attempted thoracotomy or other invasive thoracic procedure

• No evidence of small cell histology

• No evidence of hematogenous or distant metastases

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count at least 100,000/mm^3
• Absolute granulocyte count at least 2,000/mm^3
• Hemoglobin at least 8.0 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• Serum glutamate oxaloacetate transaminase (SGOT) no greater than 1.5 times upper limit of normal (unless caused by documented benign disease)

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No myocardial infarction within the past 6 months
• No symptomatic heart disease, including angina, congestive heart failure, or uncontrolled arrhythmia

Pulmonary:

• Forced expiratory volume (FEV)_1 greater than 1,000 mL

Other:

• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
• No weight loss of more than 10% in 3 months prior to diagnosis
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior thoracic or neck radiotherapy

Surgery:

• See Disease Characteristics
• No prior complete or subtotal tumor resection

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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35 participants in 13 patient groups

Arm 1

Experimental group

Description:

Sequence A: Gemcitabine 300 mg/m2/week plus radiation therapy (RT)

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Arm 2

Experimental group

Description:

Sequence B: Gemcitabine 300 mg/m2/week plus paclitaxel 30 mg/m2/week and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: paclitaxel

Arm 3

Experimental group

Description:

Sequence A: Gemcitabine 300 mg/m2/week plus carboplatin 2 AUC and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: carboplatin

Arm 4

Experimental group

Description:

Sequence B: Gemcitabine 450 mg/m2/week plus paclitaxel 30 mg/m2/week and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: paclitaxel

Arm 6

Experimental group

Description:

Sequence B: Gemcitabine 450 mg/m2/week plus paclitaxel 40 mg/m2/week and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: paclitaxel

Arm 8

Experimental group

Description:

Sequence B: Gemcitabine 600 mg/m2/week plus paclitaxel 40 mg/m2/week and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: paclitaxel

Arm 10

Experimental group

Description:

Sequence B: Gemcitabine 600 mg/m2/week plus paclitaxel 50 mg/m2/week and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: paclitaxel

Arm 12

Experimental group

Description:

Sequence B: Gemcitabine 750 mg/m2/week plus paclitaxel 50 mg/m2/week and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: paclitaxel

Arm 14

Experimental group

Description:

Sequence B: Gemcitabine 900 mg/m2/week plus paclitaxel 50 mg/m2/week and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: paclitaxel

Arm 5

Experimental group

Description:

Sequence A: Gemcitabine 450 mg/m2/week plus carboplatin 2 AUC and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: carboplatin

Arm 7

Experimental group

Description:

Sequence A: Gemcitabine 600 mg/m2/week plus carboplatin 2 AUC and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: carboplatin

Arm 9

Experimental group

Description:

Sequence A: Gemcitabine 750 mg/m2/week plus carboplatin 2 AUC and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: carboplatin

Arm 11

Experimental group

Description:

Sequence A: Gemcitabine 900 mg/m2/week plus carboplatin 2 AUC and RT

Treatment:

Drug: gemcitabine hydrochloride

Radiation: radiation therapy

Drug: carboplatin