Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Carboplatin, Paclitaxel, and Radiation Therapy With or Without Thalidomide in Treating Patients With Stage III Non-small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	ECOG-3598 E3598, NCT00004859

Special Category: CTSU trial

Objectives

1. Compare the survival and time to progression of patients with stage IIIA or IIIB non-small cell lung cancer when treated with carboplatin, paclitaxel, and chemoradiotherapy with or without thalidomide.
2. Evaluate the toxicity of the thalidomide-containing regimen and compare response rates of the two groups.
3. Determine whether the inactivation of p16, DAP-kinase, MGMT, or TIMP-3 genes can be used to predict survival in these patients treated with this regimen.
4. Determine whether the detection of a methylation biomarker in serum can be used to predict survival in these patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed newly diagnosed non-small cell bronchogenic carcinoma
  • Squamous cell
  • Adenocarcinoma
  • Large cell undifferentiated
  • Bronchoalveolar
  • Non-small cell carcinoma not otherwise stated



• Unresectable stage IIIA
  • Mediastinal lymph node enlargement of at least 1 cm but less than 2 cm on CT scans must have mediastinotomy or thoracoscopy to rule out resectability

  OR




• Stage IIIB disease without significant pleural effusion
  • Seen on CT scan only (not seen on chest x-ray) or does not reaccumulate after 1 thoracentesis and is cytologically negative
  • Metastases to contralateral, mediastinal, or supraclavicular nodes allowed



• Bidimensionally measurable or evaluable disease

Prior/Concurrent Therapy:

Biologic therapy:

• Concurrent filgrastim (G-CSF) allowed for persistent neutropenia

Chemotherapy:

• At least 5 years since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to only area of measurable or active tumor

Surgery:

• See Disease Characteristics

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count at least 100,000/mm³
• WBC at least 4,000/mm³

  OR

• Absolute neutrophil count at least 2,000/mm³

Hepatic:

• Bilirubin normal
• SGOT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No uncontrolled high blood pressure, unstable angina, congestive heart failure, or myocardial infarction within the prior year
• No serious cardiac arrhythmias requiring medication

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 methods of effective contraception for 4 weeks prior to, during, and for 4 weeks after study therapy
• No other active malignancies
• No serious uncontrolled active infection
• No evidence of greater than grade 1 neuropathy by history or physical examination
• No history of seizure disorders
• No contraindication to daily low-dose (81 mg/day) aspirin

Expected Enrollment

A total of 588 patients will be accrued for this study within 7 years.

Outcomes

Survival at median

Time to progression at median
Response rate at best response to treatment

Outline

This is a randomized study. Patients are stratified according to disease histology (squamous vs nonsquamous), performance status (0 vs 1), disease stage (IIIA vs IIIB), and time of randomization (before addition of chemoradiotherapy vs after). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive paclitaxel IV over 3 hours immediately followed by carboplatin IV over 15-30 minutes on days 1 and 22. Treatment continues every 22 days in the absence of unacceptable toxicity or disease progression.



• Arm II: Patients receive paclitaxel and carboplatin as in arm I. Patients also receive oral thalidomide and oral low-dose aspirin daily beginning on day 1 for up to 24 months in the absence of disease progression.

Beginning between days 43-50, patients in both arms with stable or responding disease receive chemoradiotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 15-30 minutes once weekly for 6 weeks and radiotherapy 5 days a week for 6 weeks. Arm II patients continue oral thalidomide.

Patients are followed every 2 months for 2 years and then every 6 months for 3 years.

Belinsky SA, Grimes MJ, Casas E, et al.: Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum. Br J Cancer 96 (8): 1278-83, 2007.[PUBMED Abstract]

Belinsky SA, Grimes M, Johnson D, et al.: Predicting gene promoter methylation in lung tumors through examination of sputum and serum. [Abstract] J Clin Oncol 24 (Suppl 18): A-7208, 416s, 2006.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Joan Schiller, MD, Protocol chair		Ph: 214-648-4180; 866-460-4673

Registry Information
Official Title		A Phase III Trial of Carboplatin, Paclitaxel and Thoracic Radiotherapy, With or Without Thalidomide, in Patients With Stage III NSCLC
Trial Start Date		2000-01-27
Registered in ClinicalTrials.gov		NCT00004859
Date Submitted to PDQ		1999-12-01
Information Last Verified		2006-10-26
NCI Grant/Contract Number		CA21115

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