Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

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

Protocol: CALGB-30610

Full Title

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

Purpose

This randomized phase III trial is comparing three different chest radiation therapy regimens to see how well they work in treating patients with limited-stage small cell lung cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as etoposide, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known which radiation therapy regimen is more effective when given together with chemotherapy in treating patients with limited-stage small cell lung cancer.

Study Objective

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.

Are you eligible?

Inclusion Criteria:

Histologically or cytologically confirmed small cell lung cancer

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

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 as >= 1 cm with spiral computed tomography (CT) scan

Patients may have received one and only one cycle of chemotherapy prior to enrolling on Cancer and Leukemia Group B (CALGB) 30610, which must have included carboplatin or cisplatin and etoposide; if a patient has had one cycle of cisplatin (or carboplatin)/etoposide prior to registration, the patient must have had all of the prior to registration tests prior to starting their first cycle of chemotherapy; additionally, these patients also must have met all of the eligibility criteria prior to receiving the first cycle of chemotherapy; registration to CALGB 30610 must take place within 14-21 days after the start of the non-protocol therapy; failing to do all of the above will make the patient NOT eligible for CALGB 30610

No prior radiotherapy or chemotherapy (except for the chemotherapy described in the bullet above) for small cell lung cancer (SCLC)

No prior mediastinal or thoracic radiotherapy

Patients with complete surgical resection of disease are not eligible

Eastern Cooperative Oncology Group (ECOG) performance status = 0-2

No patients that are known to be pregnant or nursing

Granulocytes >= 1,500/ul

Platelet count >= 100,000/ul

Total bilirubin =< 1.5 x upper limit of normal (ULN)

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.0 x ULN

Serum creatinine =< 1.5 times ULN OR creatinine clearance >= 70 mL/min

Lung Cancers