Radiation Therapy Regimens in Treating Patients With Limited-Stage Small Cell Lung Cancer Receiving Cisplatin and Etoposide

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), radiotherapy start time (at first
cycle of protocol chemotherapy, after one cycle of prior non-protocol chemotherapy vs at
first cycle of protocol chemotherapy, without prior non-protocol chemotherapy vs at second
cycle of protocol chemotherapy, without prior non-protocol chemotherapy) and chemotherapy
backbone: carboplatin vs cisplatin.

OBJECTIVES:

Primary Objective

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 Objectives

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

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

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

4. To compare patients' quality of life between these treatment regimens in terms of their
physical symptoms, physical functioning and psychological state

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

6. To examine blood-based biomarkers of response and resistance to cisplatin (or
carboplatin) and etoposide

7. To evaluate the correspondence between increases in plasma ProGRP concentrations and
disease progression/recurrence

8. 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
PFS and OS

9. To evaluate the correspondence between longitudinal decreases in plasma ProGRP
concentrations and clinical response

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 or
carboplatin IV 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 or carboplatin and
etoposide as in arm I.

Arm III: (discontinued as of 03/10/13) Patients undergo mid-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.

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. Please see the
Arms section for more information regarding Part 2.

Prophylactic cranial irradiotherapy (PCI): Within 3-6 weeks after completion of chemotherapy,
PCI should be offered to all patients with a complete tumor response (CR) or near complete
response (nCR) with only residual chest abnormalities of indeterminate nature following
completion of combined modality therapy.

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.

1. Documentation of Disease

1. Histologically or cytologically documented small cell lung cancer (SCLC)

2. Limited-stage disease patients with disease restricted to one hemithorax with
regional lymph node metastases, including ipsilateral hilar, ipsilateral and
contralateral mediastinal, and ipsilateral supraclavicular lymph nodes

- Patients with disease involvement of the contralateral hilar or
supraclavicular lymph nodes are not eligible

- Patients with pleural effusions that are visible on plain chest radiographs,
whether cytologically positive or not are not eligible unless they have a
negative thoracentesis

- Patients with cytologically positive pleural or pericardial fluid,
regardless of the appearance on plain x-ray are not eligible

2. Measurable disease - Patients must have measurable disease, which includes lesions
that can be accurately measured in at least one dimension (longest diameter to be
recorded) as ≥ 2 cm with conventional techniques OR ≥ 1 cm by spiral CT scan

3. Prior Treatment

1. Patients may have received one and only one cycle of chemotherapy prior to
enrolling on CALGB 30610, which must have included carboplatin or cisplatin and
etoposide.

2. If a patient has had one cycle of cisplatin or carboplatin/etoposide prior to
registration, the patient must have had all of it prior to registration tests as
outlined in the protocol and prior to starting their first cycle of chemotherapy.

3. Additionally, these patients also must have met all of the eligibility criteria
in the protocol prior to receiving the first cycle of chemotherapy.

4. Registration to CALGB 30610 must take place within 14-21 days after the start of
the non-protocol therapy.

5. Failing to do all of the above will make the patient NOT eligible for CALGB
30610.

6. No prior radiotherapy or chemotherapy (except for the chemotherapy described in
the bullet above) for SCLC

7. No prior mediastinal or thoracic radiotherapy

8. Patients with complete surgical resection of disease are not eligible

4. Age Requirement ≥ 18 years of age

5. ECOG Performance Status 0-2

6. Non-pregnant and non-nursing - No patients that are known to be pregnant or nursing

7. Required Initial Laboratory Values

1. Granulocytes ≥ 1,500/µl

2. Platelet count ≥ 100,000/µl

3. Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

4. AST (SGOT) ≤ 2.0 times ULN

5. Serum creatinine ≤ 1.5 times ULN OR Calculated creatinine clearance ≥ 70 mL/min