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

Tracking Information
First Submitted Date ICMJE	March 8, 2008
First Posted Date ICMJE	March 11, 2008
Last Update Posted Date	June 12, 2018
Study Start Date ICMJE	March 2008
Estimated Primary Completion Date	June 2023 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: August 10, 2015)	Overall survival time between 3 treatment arms [ Time Frame: Up to 5 years ]
Original Primary Outcome Measures ICMJE; (submitted: March 8, 2008)	Overall survival time between 3 treatment arms
Change History	Complete list of historical versions of study NCT00632853 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: August 10, 2015)	Complete and partial response rates [ Time Frame: Up to 5 years ]; Failure-free survival [ Time Frame: Up to 5 years ]
Original Secondary Outcome Measures ICMJE; (submitted: March 8, 2008)	Toxicity; Complete and partial response rates; Failure-free survival; Local tumor progression according to RECIST criteria; Rates of distant metastases and intracranial metastases
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Radiation Therapy Regimens in Treating Patients With Limited-Stage Small Cell Lung Cancer Receiving Cisplatin and Etoposide
Official Title ICMJE	Phase III Comparison of Thoracic Radiotherapy Regimens in Patients With Limited Small Cell Lung Cancer Also Receiving Cisplatin and Etoposide
Brief Summary	Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as etoposide, carboplatin and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. This randomized phase III trial is comparing different chest radiation therapy regimens to see how well they work in treating patients with limited-stage small cell lung cancer.
Detailed Description	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; 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 compare patients' quality of life between these treatment regimens in terms of their physical symptoms, physical functioning and psychological state; To describe the patterns of use of thoracic intensity modulated radiation therapy (IMRT) in patients with limited stage small cell lung cancer; To examine blood-based biomarkers of response and resistance to cisplatin (or carboplatin) and etoposide; To evaluate the correspondence between increases in plasma ProGRP concentrations and disease progression/recurrence; 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; 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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Lung Cancer
Intervention ICMJE	Radiation: Standard Radiation Dose Therapy 45 Gy; Drug: cisplatin IV; Drug: etoposide IV; Radiation: High Radiation Dose Therapy 70 Gy; Drug: carboplatin IV
Study Arms	Active Comparator: Arm A - Standard Radiotherapy + Chemotherapy Radiotherapy (every day, Monday-Friday, for a total of 3 weeks) XRT: 45 Gy BID (1.5 Gy/fx) starting on day 1 of Cycle 1 or 2, every day, for 3 weeks Chemotherapy (every 21 days for 4 cycles, for a total of 12 weeks): Cisplatin 80 mg/m2 IV on day 1 OR Carboplatin AUC 5 IV day 1, every 21 days Etoposide 100 mg/m2 IV Register/ on days 1, 2, and 3, every 21 days Interventions: Radiation: Standard Radiation Dose Therapy Drug: cisplatin Drug: etoposide Drug: carboplatin; Experimental: Arm B - High Dose Radiotherapy + Chemotherapy Radiotherapy (every day, Monday-Friday, for a total of 7 weeks) XRT: 70 Gy QD (2.0 Gy/fx), starting on day 1 of Cycle 1 or 2, every day, for 7 weeks Chemotherapy (every 21 days for 4 cycles, for a total of 12 weeks): Cisplatin 80 mg/m2 IV on day 1 OR Carboplatin AUC 5 IV day 1, every 21 days Etoposide 100 mg/m2 IV on days 1, 2, and 3, every 21 days Interventions: Drug: cisplatin Drug: etoposide Radiation: High Radiation Dose Therapy Drug: carboplatin
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: February 14, 2013)	729
Original Enrollment ICMJE; (submitted: March 8, 2008)	712
Study Completion Date	Not Provided
Estimated Primary Completion Date	June 2023 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Documentation of Disease Histologically or cytologically documented small cell lung cancer (SCLC) 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; 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; Prior Treatment 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. 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. Additionally, these patients also must have met all of the eligibility criteria in the protocol 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 SCLC No prior mediastinal or thoracic radiotherapy Patients with complete surgical resection of disease are not eligible; Age Requirement ≥ 18 years of age; ECOG Performance Status 0-2; Non-pregnant and non-nursing - No patients that are known to be pregnant or nursing; Required Initial Laboratory Values Granulocytes ≥ 1,500/µl Platelet count ≥ 100,000/µl Total bilirubin ≤ 1.5 times upper limit of normal (ULN) AST (SGOT) ≤ 2.0 times ULN Serum creatinine ≤ 1.5 times ULN OR Calculated creatinine clearance ≥ 70 mL/min
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Jeffrey A. Bogart, MD 315 464-5276
Listed Location Countries ICMJE	Israel, Korea, Republic of, Puerto Rico, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00632853
Other Study ID Numbers ICMJE	CALGB-30610; CALGB-30610 ( Other Identifier: Cancer and Leukemia Group B ); RTOG 0538 ( Other Identifier: Radiation Therapy Oncology Group ); U10CA031946 ( U.S. NIH Grant/Contract ); CDR0000588879 ( Registry Identifier: Physician Data Query ); NCI-2009-00470 ( Registry Identifier: NCI Clinical Trials Reporting Program )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Alliance for Clinical Trials in Oncology
Study Sponsor ICMJE	Alliance for Clinical Trials in Oncology
Collaborators ICMJE	National Cancer Institute (NCI)
Investigators ICMJE	Study Chair: Jeffrey A. Bogart, MD State University of New York - Upstate Medical University
PRS Account	Alliance for Clinical Trials in Oncology
Verification Date	June 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP