Radiation Therapy Regimens in Treating Patients With Limited-Stage Small Cell Lung Cancer Receiving Cisplatin and Etoposide
- Conditions
- Lung Cancer
- Interventions
- Radiation: Standard Radiation Dose TherapyRadiation: High Radiation Dose Therapy
- Registration Number
- NCT00632853
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- 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
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 731
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A - Standard Radiotherapy + Chemotherapy Standard Radiation Dose Therapy 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 Arm A - Standard Radiotherapy + Chemotherapy etoposide 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 Arm B - High Dose Radiotherapy + Chemotherapy High Radiation Dose Therapy 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 Arm A - Standard Radiotherapy + Chemotherapy cisplatin 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 Arm A - Standard Radiotherapy + Chemotherapy carboplatin 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 Arm B - High Dose Radiotherapy + Chemotherapy cisplatin 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 Arm B - High Dose Radiotherapy + Chemotherapy etoposide 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 Arm B - High Dose Radiotherapy + Chemotherapy carboplatin 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
- Primary Outcome Measures
Name Time Method Overall Survival Time 11.25 years Overall survival time is defined as the time between a patient's registration and death or end of survival follow up.
- Secondary Outcome Measures
Name Time Method Complete and Partial Response Rates 11.25 years Failure-free >> Survival Up to 5 years To Examine Blood-based Biomarkers of Response and Resistance to Cisplatin (or Carboplatin) and Etoposide. 5 years To Compare Rates of Local Relapse, Distant Metastases and Brain Metastases With These > Regimens. 5 years To Compare Patients' Quality of Life Between These Treatment Regimens in Terms of Their > Physical Symptoms, Physical Functioning and Psychological State. 5 years To Describe the Patterns of Use of Thoracic Intensity Modulated Radiation Therapy (IMRT) in Patients With Limited Stage Small Cell Lung Cancer. 5 years To Evaluate the Correspondence Between Increases in Plasma ProGRP Concentrations and Disease Progression/Recurrence 5 years To Evaluate the Correspondence Between Longitudinal Decreases in Plasma ProGRP Concentrations and Clinical Response. 5 years 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. 5 years
Trial Locations
- Locations (931)
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
The Kirklin Clinic at Acton Road
🇺🇸Birmingham, Alabama, United States
Providence Hospital
🇺🇸Mobile, Alabama, United States
Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
🇺🇸Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
🇺🇸Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸Anchorage, Alaska, United States
Alaska Regional Hospital
🇺🇸Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸Anchorage, Alaska, United States
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