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Pemetrexed Disodium, Carboplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Stage III Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborators:
Eli Lilly and Company
Bristol-Myers Squibb
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00117962
First received: July 8, 2005
Last updated: November 14, 2014
Last verified: November 2014
  Purpose

RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also make tumor cells more sensitive to radiation therapy. Giving pemetrexed disodium, carboplatin, and radiation therapy together with cetuximab may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving pemetrexed disodium and carboplatin together with radiation therapy with or without cetuximab works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery.


Condition Intervention Phase
Lung Cancer
Biological: cetuximab
Drug: carboplatin
Drug: pemetrexed disodium
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Radiation Therapy, Pemetrexed and Carboplatin With or Without Cetuximab in Stage III Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • 18 Month Survival [ Time Frame: 18 months (from randomization) ] [ Designated as safety issue: No ]
    Percentage of participants who were alive at 18 months. The 18 month survival, with 95% CI, was estimated using the Kaplan-Meier method.


Secondary Outcome Measures:
  • Failure-free Survival [ Time Frame: Time from randomization to failure (up to 4 years) ] [ Designated as safety issue: No ]
    Failure-free survival (FFS) is the time from randomization to a failure event, defined as disease progression or death from any cause (which ever occurred first). The median FFS with 95% CI was estimated using the Kaplan-Meier method,

  • Number of Participants With Overall Tumor Response [ Time Frame: Duration of study until progression (up to 4 years) ] [ Designated as safety issue: No ]

    Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:

    • Complete Response (CR): disappearance of all target lesions;
    • Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;
    • Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions;
    • Stable Disease (SD): small changes that do not meet above criteria.

    Overall tumor response is the total number of CR and PRs.



Other Outcome Measures:
  • Overall Survival [ Time Frame: Time from randomization to death (up to 4 years) ] [ Designated as safety issue: No ]
    Overall survival (OS) is defined as the time from patient randomization (arm assignment) to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.


Enrollment: 109
Study Start Date: September 2005
Study Completion Date: September 2012
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Std Tx + Pemetrexed
Patients receive pemetrexed disodium IV over 10 minutes followed by carboplatin IV over 30 minutes on days 1, 22, 43, and 64. Patients also undergo thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.
Drug: carboplatin
AUC = 5 q 21 days for 4 cycles
Drug: pemetrexed disodium
500 mg/sq m IV q 21 days during chemoradiation and consolidation chemotherapy phases
Radiation: radiation therapy
Thoracic radiotherapy: 70 Gy for 7 weeks beginning on Day 1.
Experimental: Std Tx + Pemetrexed and Cetuximab
Patients receive pemetrexed disodium, carboplatin, and thoracic radiotherapy as in arm I. Patients also receive cetuximab IV over 2 hours on day 1 and then IV over 1 hour on days 8, 15, 22, 29, 36, and 43.
Biological: cetuximab
400 mg/sq m IV over 120 min: Day 1; Week 1 250 mg/sq m IV over 60 min weekly for 6 more weeks.
Drug: carboplatin
AUC = 5 q 21 days for 4 cycles
Drug: pemetrexed disodium
500 mg/sq m IV q 21 days during chemoradiation and consolidation chemotherapy phases
Radiation: radiation therapy
Thoracic radiotherapy: 70 Gy for 7 weeks beginning on Day 1.

Detailed Description:

OBJECTIVES:

Primary

  • Determine the overall survival of patients with unresectable stage III non-small cell lung cancer treated with pemetrexed disodium, carboplatin, and thoracic radiotherapy with or without cetuximab.

Secondary

  • Determine the failure-free survival and response rates in patients treated with these regimens.
  • Correlate epidermal growth factor receptor, erbB2, and K-ras mutations with survival and tumor response in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study.

  • Chemoradiotherapy (courses 1-4): Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive pemetrexed disodium IV over 10 minutes followed by carboplatin IV over 30 minutes on days 1, 22, 43, and 64. Patients also undergo thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.
    • Arm II: Patients receive pemetrexed disodium, carboplatin, and thoracic radiotherapy as in arm I. Patients also receive cetuximab IV over 2 hours on day 1 and then IV over 1 hour on days 8, 15, 22, 29, 36, and 43.
  • Consolidation chemotherapy (courses 5-8): Beginning 3-5 weeks after completion of chemoradiotherapy, all patients receive consolidation chemotherapy comprising pemetrexed disodium alone IV over 10 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study within 10-13 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  1. Histologically or cytologically documented NSCLC, including squamous cell carcinoma, adenocarcinoma including bronchoalveolar cell, and large cell anaplastic carcinoma (including giant and clear cell carcinomas)
  2. Eligible Disease Stages: Inoperable IIIA and Selected IIIB - Patients entered must be considered unresectable or inoperable. Patients do not need to have a mediastinoscopy.

    A size of 2 cm or greater by CT is a sufficient criterion for the diagnosis of mediastinal lymph node (N2 or N3) involvement by malignancy. If the largest mediastinal lymph node is less than 2 cm in diameter, a biopsy confirmation of mediastinal nodal involvement is required.

    1. The following patients are eligible:

      • Patients must be M0
      • Patients with any T with N2 or N3 are eligible
      • Patients with T3, N1-N3 disease are eligible if deemed unresectable
      • Patients with T4, any N are eligible provided the T4 status is not determined because of malignant effusion
      • Patients with contralateral mediastinal disease (N3) are eligible if all gross disease can be encompassed in the radiation field in accordance with the homogeneity criteria
      • Patients with a pleural effusion, which is a transudate, cytologically negative and non-bloody, are eligible if the radiation oncologist feels the tumor can be encompassed within a reasonable field of radiotherapy
      • If a pleural effusion can be seen on the chest CT but not on CXR and is too small to tap, the patient will be eligible. Patients who develop a new pleural effusion after thoracotomy or other invasive thoracic procedure will be eligible.
    2. The following patients are NOT eligible:

      • Patients with T3, N0 disease
      • Patients with M1 disease
      • Patients with atelectasis of the entire lung
      • Patients with direct invasion of vertebral body
      • Patients with scalene, supraclavicular, or contralateral hilar node involvement
      • Patients with exudative, bloody, or cytologically malignant effusions
  3. Patients must have Measurable Disease: Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥10 mm with spiral CT scan. Lesions that are not considered measurable include bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusion, abdominal masses that are not confirmed and followed by imaging techniques, cystic lesions and tumor lesions situated in a previously irradiated area.
  4. Prior Therapy: ≥ 2 weeks since formal exploratory thoracotomy. No prior chemotherapy for NSCLC, chest radiation therapy or therapy that specifically and directly targets the EGFR pathway
  5. ECOG performance status 0-1
  6. Positron Emission Tomography (PET) using 18 fluorodeoxyglucose (FDG) must be negative for distant metastasis. PET imaging is mandatory.
  7. Weight loss of ≤ 10% in the past 3 months
  8. No "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse.
  9. Non-pregnant and non-nursing because of significant risk to the fetus/infant
  10. Age ≥ 18 years
  11. No patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness.
  12. No HIV-positive patients receiving combination anti-retroviral therapy because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy
  13. No known history of hypersensitivity to carboplatin, pemetrexed or a monoclonal antibody
  14. Required Initial Laboratory Values:

    1. Granulocytes ≥ 1,500/mcl
    2. Platelets ≥ 100,000/mcl
    3. Calculated Creatinine Clearance ≥ 45 ml/min
    4. Bilirubin < 1.5 x ULN
    5. AST/ALT < 3 x ULN
    6. Alkaline Phosphatase < 3 x ULN
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00117962

  Show 71 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Eli Lilly and Company
Bristol-Myers Squibb
Investigators
Study Chair: Ramaswamy Govindan, MD Washington University School of Medicine
  More Information

Additional Information:
Publications:
Govindan R, Bogart J, Wang X, et al.: Phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small cell lung cancer: CALGB 30407. [Abstract] J Clin Oncol 27 (Suppl 15): A-7505, 2009.
Govindan R, Bogart J, Wang X, et al.: A phase II study of pemetrexed, carboplatin and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small cell lung cancer: CALGB 30407--early evaluation of feasibility and toxicity. [Abstract] J Clin Oncol 26 (Suppl 15): A-30407, 2008.

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00117962     History of Changes
Other Study ID Numbers: CALGB 30407, U10CA031946, CDR0000434616
Study First Received: July 8, 2005
Results First Received: November 5, 2012
Last Updated: November 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
squamous cell lung cancer
large cell lung cancer
adenocarcinoma of the lung
bronchoalveolar cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Cetuximab
Pemetrexed
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014