Pemetrexed Disodium, Carboplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:
NCT00117962
First received: July 8, 2005
Last updated: December 10, 2012
Last verified: December 2012
  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 Cancer and Leukemia Group B:

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including any of the following subtypes:

    • Squamous cell carcinoma
    • Adenocarcinoma (including bronchoalveolar cell carcinoma)
    • Large cell anaplastic carcinoma (including giant cell and clear cell carcinoma)
  • Stage IIIA OR selected stage IIIB disease*

    • Any T, N2-3, M0 disease
    • T3, N1-3, M0 disease allowed provided disease is unresectable
    • T4, any N, M0 disease allowed provided T4 status cannot be determined due to malignant effusion
    • No T3, N0, M0 disease NOTE: *If the largest mediastinal lymph node is < 2 cm in diameter by CT scan, a biopsy confirmation of mediastinal nodal involvement is required
  • Unresectable disease
  • Contralateral mediastinal disease (N3) allowed provided all gross disease can be encompassed within the radiation field in accordance with the homogeneity criteria
  • Measurable disease, defined as ≥ 1 one-dimensional measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

    • The following are not considered measurable disease:

      • Bone lesions
      • Leptomeningeal disease
      • Ascites
      • Pleural or pericardial effusion
      • Abdominal masses not confirmed and followed by imaging techniques
      • Cystic lesions
      • Tumor lesions in a previously irradiated area
  • No exudative, bloody, or cytologically positive malignant effusion

    • Transudate, cytologically negative, non-bloody pleural effusion allowed provided the tumor can be encompassed within a reasonable field of radiotherapy
    • Pleural effusion detectable by chest CT scan but not by chest x-ray that is too small to tap
    • New pleural effusion appearing after thoracotomy or other invasive thoracic procedure allowed
  • No atelectasis of the entire lung
  • No direct invasion of the vertebral body
  • No scalene, supraclavicular, or contralateral hilar node involvement
  • No distant metastases (M1) by fludeoxyglucose F18 positron emission tomography

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT < 3 times ULN
  • Alkaline phosphatase < 3 times ULN

Renal

  • Creatinine clearance ≥ 45 mL/min

Cardiovascular

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Other

  • Not pregnant or nursing
  • Weight loss ≤ 10% within the past 3 months
  • No other active* malignancy except nonmelanoma skin cancer
  • No ongoing or active infection
  • No other uncontrolled illness
  • No history of hypersensitivity to carboplatin, pemetrexed disodium, or a monoclonal antibody NOTE: *Malignancy is not considered active if the patient has completed treatment and has < 30% risk of relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent filgrastim (G-CSF), pegfilgrastim, or sargramostim (GM-CSF) during thoracic radiotherapy or as prophylaxis for myelosuppression

Chemotherapy

  • No prior chemotherapy for NSCLC
  • No other concurrent chemotherapy

Endocrine therapy

  • No concurrent hormonal therapy except megestrol for appetite stimulation or dexamethasone to prevent rash from pemetrexed disodium

Radiotherapy

  • No prior radiotherapy to the chest
  • No concurrent palliative radiotherapy
  • No concurrent intensity modulated radiotherapy

Surgery

  • See Disease Characteristics
  • At least 2 weeks since prior formal exploratory thoracotomy

Other

  • No prior therapy that directly targets the epidermal growth factor receptor pathway
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00117962

  Show 71 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Ramaswamy Govindan, MD Washington University Siteman Cancer Center
Study Director: Jeffrey A. Bogart, MD State University of New York - Upstate Medical University
  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: Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00117962     History of Changes
Other Study ID Numbers: CDR0000434616, U10CA031946, CALGB-30407
Study First Received: July 8, 2005
Results First Received: November 5, 2012
Last Updated: December 10, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Cancer and Leukemia Group B:
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
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Cetuximab
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on April 15, 2014