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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 That Cannot Be Removed By Surgery
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00117962
  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
Drug: carboplatin
Drug: cetuximab
Drug: pemetrexed disodium
Procedure: radiation therapy
Phase II

MedlinePlus related topics: Cancer Lung Cancer
Drug Information available for: Carboplatin Pemetrexed disodium Pemetrexed Cetuximab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Failure-free survival [ Designated as safety issue: No ]
  • Response rate [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: September 2005
Estimated Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Experimental
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
Given IV
Drug: pemetrexed disodium
Given IV
Procedure: radiation therapy
Thoracic radiotherapy
Arm II: Experimental
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.
Drug: carboplatin
Given IV
Drug: cetuximab
Given IV
Drug: pemetrexed disodium
Given IV
Procedure: radiation therapy
Thoracic radiotherapy

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 and erbB2 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 unidimensionally 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 allowed
    • 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
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Weight loss ≤ 10% within the past 3 months
  • No other active* malignancy except nonmelanoma skin cancer
  • No ongoing or active infection
  • No psychiatric illness
  • 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 Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Investigator: Jeffrey A. Bogart, MD State University of New York - Upstate Medical University
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
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.

Study ID Numbers: CDR0000434616, CALGB-30407
Study First Received: July 8, 2005
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00117962  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Study placed in the following topic categories:
Thoracic Neoplasms
Non-small cell lung cancer
Adenocarcinoma, Bronchiolo-Alveolar
Cetuximab
Carboplatin
Carcinoma
Folic Acid
Pemetrexed
Adenocarcinoma of lung
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Adenocarcinoma
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Antimetabolites
Respiratory Tract Neoplasms
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Folic Acid Antagonists
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009