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

• ClinicalTrials.gov Identifier: NCT00632853
• Recruitment Status: Active, not recruiting
• First Posted: March 11, 2008
• Results First Posted: June 12, 2023
• Last Update Posted: June 12, 2023
• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Alliance for Clinical Trials in Oncology

Tracking Information

• First Submitted Date: March 8, 2008
• First Posted Date: March 11, 2008
• Results First Submitted Date: April 28, 2023
• Results First Posted Date: June 12, 2023
• Last Update Posted Date: June 12, 2023
• Actual Study Start Date: March 2008
• Actual Primary Completion Date: March 2, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 8, 2023)

Overall Survival Time [ Time Frame: 11.25 years ]

Overall survival time is defined as the time between a patient's registration and death or end of survival follow up.

• Original Primary Outcome Measures (submitted: March 8, 2008): Overall survival time between 3 treatment arms

Current Secondary Outcome Measures (submitted: June 8, 2023)

• Complete and Partial Response Rates [ Time Frame: 11.25 years ]
• Failure-free >> Survival [ Time Frame: Up to 5 years ]
• To Compare Rates of Local Relapse, Distant Metastases and Brain Metastases With These > Regimens. [ Time Frame: 5 years ]
• To Compare Patients' Quality of Life Between These Treatment Regimens in Terms of Their > Physical Symptoms, Physical Functioning and Psychological State. [ Time Frame: 5 years ]
• To Describe the Patterns of Use of Thoracic Intensity Modulated Radiation Therapy (IMRT) in Patients With Limited Stage Small Cell Lung Cancer. [ Time Frame: 5 years ]
• To Examine Blood-based Biomarkers of Response and Resistance to Cisplatin (or Carboplatin) and Etoposide. [ Time Frame: 5 years ]
• To Evaluate the Correspondence Between Increases in Plasma ProGRP Concentrations and Disease Progression/Recurrence [ Time Frame: 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. [ Time Frame: 5 years ]
• To Evaluate the Correspondence Between Longitudinal Decreases in Plasma ProGRP Concentrations and Clinical Response. [ Time Frame: 5 years ]

Original Secondary Outcome Measures (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Radiation Therapy Regimens in Treating Patients With Limited-Stage Small Cell Lung Cancer Receiving Cisplatin and Etoposide
• Official Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lung Cancer

Intervention

• 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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 7, 2020): 731
• Original Enrollment (submitted: March 8, 2008): 712
• Study Completion Date: Not Provided
• Actual Primary Completion Date: March 2, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel, Korea, Republic of, Puerto Rico, United States

Administrative Information

• NCT Number: NCT00632853
• Other Study ID Numbers: 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
• Current Responsible Party: Alliance for Clinical Trials in Oncology
• Original Responsible Party: Not Provided
• Current Study Sponsor: Alliance for Clinical Trials in Oncology
• Original Study Sponsor: Cancer and Leukemia Group B
• Collaborators: National Cancer Institute (NCI)

Investigators

• 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 2023