Three Different Radiation Therapy Regimens in Treating Patients with Limited-Stage Small Cell Lung Cancer Receiving Cisplatin or Carboplatin and Etoposide

Summary

Objectives

PRIMARY OBJECTIVES:
I. To determine whether administering high-dose thoracic radiotherapy, 70 Gray (Gy) (2 Gy once daily over 7 weeks) or 61.2 Gy (1.8 Gy once daily for 16 days followed by 1.8 Gy twice daily for 9 days), will improve median and 2-year survival compared with 45 Gy (1.5 Gy twice daily over 3 weeks) in patients with limited-stage small cell lung cancer.

SECONDARY OBJECTIVES:
I. To compare treatment-related toxic effects of thoracic radiotherapy regimens in patients with limited-stage small cell lung cancer.
II. To compare response rates, failure-free survival, and toxicity of thoracic radiotherapy regimens in patients with limited-stage small cell lung cancer.
III. To compare rates of local relapse, distant metastases, and brain metastases with these regimens.
IV. To compare patients’ quality of life between these treatment regimens in terms of their physical symptoms, physical functioning and psychological state.
V. To describe the patterns of use of thoracic intensity modulated radiation therapy (IMRT) in patients with limited stage small cell lung cancer.
VI. To examine blood-based biomarkers of response and resistance to cisplatin (or carboplatin) and etoposide.
VII. To evaluate the correspondence between increases in plasma pro-gastrin-releasing peptide (proGRP) concentrations and disease progression/recurrence.
VIII. To evaluate the potential for plasma proGRP concentrations at baseline, after each cycle of chemotherapy and at first evaluation following completion of chemotherapy to predict progression-free survival (PFS) and overall survival (OS).
IX. To evaluate the correspondence between longitudinal decreases in plasma proGRP concentrations and clinical response.

OUTLINE:
PART 1: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients undergo standard-dose (45 Gy given in 30 treatments) thoracic radiotherapy twice daily (BID), 5 days a week, for 3 weeks. Patients also receive cisplatin intravenously (IV) or carboplatin IV on day 1 and etoposide IV on days 1, 2, and 3.

ARM II: Patients undergo higher-dose (70 Gy given in 35 treatments) thoracic radiotherapy once daily (QD), 5 days a week, for 7 weeks. Patients also receive cisplatin or carboplatin and etoposide as in Arm I.

ARM III (CLOSED TO ACCRUAL AS OF 3/10/13): Patients undergo higher-dose (61.2 Gy given in 34 treatments) thoracic radiotherapy QD, 5 days a week, during the initial 16 days (approximately 3 weeks) of treatment and then BID, 5 days a week, for the final 9 days (approximately 2 weeks) of treatment. Patients also receive cisplatin or carboplatin and etoposide as in Arm I.

In all arms, treatment with cisplatin or carboplatin and etoposide repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

PART 2: An interim analysis, conducted after accrual of 30 patients per arm, selected one experimental arm based upon a comparison of treatment-related toxicity. The most toxic experimental arm (Arm C) was discontinued, and the trial continued comparing standard therapy (Arm I) to the selected experimental regimen (Arm II).

PROPHYLACTIC CRANIAL IRRADIATION (PCI): Within 3-6 weeks after completion of chemotherapy, patients with a complete tumor response (complete response [CR]) or near complete response (very good partial response [PR]) with only residual chest abnormalities of indeterminate nature are eligible to undergo prophylactic radiotherapy to the brain QD, 5 days a week, for 2 weeks. Patients with a response to therapy that is less than CR or very good PR may undergo PCI at the investigator’s discretion.

After completion of study treatment, patients are followed up at least every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years or until disease progression. At disease progression, patients are followed up every 6 months.