Radiation Therapy Combined With Paclitaxel and Carboplatin in Treating Patients With Stage III Non-Small Cell Lung Cancer

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 2; Phase 1

Conditions: Lung Cancer

Treatments: Radiation: three-dimensional conformal radiation therapy; Drug: paclitaxel; Drug: carboplatin

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00023673

CDR0000068850 (Registry Identifier)

NCI-2012-02401 (Registry Identifier)

RTOG L-0117

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them with specialized radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the effectiveness of radiation therapy combined with paclitaxel and carboplatin in treating patients who have stage III non-small cell lung cancer.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose of 3-dimensional conformal radiotherapy when administered concurrently with paclitaxel and carboplatin in patients with inoperable stage IIIA or IIIB non-small cell lung cancer. (Phase I) (Closed to accrual as of 01/13/04.)
• Determine the 12-month survival rate in patients treated with this regimen. (Phase II) (Closed to accrual as of 11/27/07.)
• Determine the toxicity of this regimen in these patients.
• Determine the partial organ tolerance doses for the lung and esophagus in patients treated with this regimen.
• Determine the complete response rate in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of 3-dimensional conformal radiotherapy.

• Phase I (closed to accrual as of 01/13/04): Patients undergo 3-dimensional conformal radiotherapy once daily five days a week for 7-8 weeks. Patients also receive concurrent chemotherapy comprising paclitaxel IV over 1 hour followed by carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43.

Cohorts of 7-9 patients receive de-escalating doses of 3-dimensional conformal radiotherapy until the maximum tolerated dose (MTD) is determined when given in combination with chemotherapy. The MTD is defined as the highest dose at which no more than 1 patient experiences dose-limiting toxicity.

• Phase II: Additional patients are accrued and treated as above at the MTD. At least 3 weeks after completing radiotherapy, patients may receive additional chemotherapy comprising paclitaxel IV over 3 hours once and carboplatin IV over 30 minutes once. Treatment with paclitaxel and carboplatin may repeat every 3 weeks for up to 2 courses.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3-5 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 73 patients (up to 27 for phase I [closed to accrual as of 10/28/04] and 46 for phase II) will be accrued for this study within 1-1.5 years.

Enrollment: 63 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed unresectable stage IIIB non-small cell lung cancer

  • Squamous cell carcinoma
  • Adenocarcinoma
  • Large cell carcinoma
  • Non-small cell carcinoma not otherwise specified

• All detectable primary tumor and involved regional lymph nodes must be encompassed by radiotherapy fields

• Measurable disease on 3-dimensional planning CT scan

• No undifferentiated small cell (oat cell or high-grade neuroendocrine) carcinoma

• No stage IV or recurrent disease

• No distant metastases or supraclavicular lymph node involvement

• No significant atelectasis (i.e., atelectasis of an entire lung)

• No pleural effusions, pericardial effusions, or superior vena cava syndrome

• No lung cancer within the past 2 years

• Ineligible for currently open Radiation Therapy Oncology Group (RTOG) phase III lung protocols

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin less than 1.5 mg/dL
• Aspartate aminotransferase (AST) less than 2 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Pulmonary:

• Forced expiratory volume (FEV)_1 at least 1.0 L

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No weight loss greater than 5% in the past 6 months
• No other malignancy within the past year except nonmelanoma skin cancer
• Completed 3D plan with total lung V20 </= 30% mean esophageal dose </= 34 Gy and esophageal V55 </= 30%

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic response modifiers for current lung cancer
• At least 5 years since prior biologic response modifiers

Chemotherapy:

• No prior chemotherapy for current lung cancer
• At least 5 years since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to the thorax

Surgery:

• No prior complete tumor resection

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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63 participants in 4 patient groups

Phase I: 75.25 Gy/36 fx + chemotherapy

Experimental group

Description:

Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.

Treatment:

Radiation: three-dimensional conformal radiation therapy

Drug: carboplatin

Drug: paclitaxel

Phase I: 74 Gy/37 fx + chemotherapy

Experimental group

Description:

Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.

Treatment:

Radiation: three-dimensional conformal radiation therapy

Drug: carboplatin

Drug: paclitaxel

Phase I: 70 Gy/35 fx + chemotherapy

Experimental group

Description:

Phase I: Three-dimensional conformal radiation therapy (3DRT) of 70 Gy given in 35 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.

Treatment:

Radiation: three-dimensional conformal radiation therapy

Drug: carboplatin

Drug: paclitaxel

Phase II: 74 Gy/37 fx + chemotherapy

Experimental group

Description:

Phase II: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.

Treatment:

Radiation: three-dimensional conformal radiation therapy

Drug: carboplatin

Drug: paclitaxel