Trial Information

Phase III Comparison of Thoracic Radiotherapy Regimens in Patients With Limited Small Cell Lung Cancer Also Receiving Cisplatin and Etoposide

OBJECTIVES:

Primary

- To determine whether administering high-dose thoracic radiotherapy, 70 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

- To compare treatment-related toxic effects of thoracic radiotherapy regimens in
patients with limited-stage small cell lung cancer.

- To compare response rates, failure-free survival, and toxicity of thoracic radiotherapy
regimens in patients with limited-stage small cell lung cancer.

- To compare rates of local relapse, distant metastases, and brain metastases with these
regimens.

- To describe the patterns of use of thoracic intensity-modulated radiotherapy (IMRT) in
patients with limited-stage small cell lung cancer.

OUTLINE: This is a 2-part, multicenter, randomized study. Patients are stratified according
to gender, weight loss 6 months prior to study entry (≤ 5% of body weight vs > 5% of body
weight), ECOG performance status (0 vs 1 vs 2), radiotherapy technique (intensity-modulated
radiotherapy vs 3-dimensional conformal radiotherapy), and radiotherapy start time (at first
course of protocol chemotherapy, after one course of prior non-protocol chemotherapy vs at
first course of protocol chemotherapy, without prior non-protocol chemotherapy vs at second
course of protocol chemotherapy, without prior non-protocol chemotherapy).

- 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, 5 days a week, for 3 weeks. Patients also receive
cisplatin 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, 5 days a week, for 7 weeks. Patients also receive
cisplatin and etoposide as in arm I.

- Arm III: (discontinued as of 03/10/13) Patients undergo higher-dose (61.2 Gy given
in 34 treatments) thoracic radiotherapy once daily, 5 days a week, during the
initial 16 days (approximately 3 weeks) of treatment and then twice daily, 5 days
a week, for the final 9 days (approximately 2 weeks) of treatment. Patients also
receive cisplatin and etoposide as in arm I.

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

- Part 2: An interim analysis was conducted after accrual of 30 patients per arm and one
experimental arm based upon a comparison of treatment-related toxicity was selected.
The most toxic experimental arm was discontinued, and the trial continues comparing
standard therapy (arm I) to the selected experimental regimen (arm II) as described in
part 1.

Prophylactic radiotherapy: Within 3-6 weeks after completion of chemotherapy, patients with
responding disease are eligible to undergo prophylactic radiotherapy to the brain once a
day, 5 days a week, for 2 weeks.

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.