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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

Phase 2
Completed
Conditions
Lung Cancer
Interventions
Biological: cetuximab
Radiation: radiation therapy
Registration Number
NCT00117962
Lead Sponsor
Alliance for Clinical Trials in Oncology
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
109
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Std Tx + Pemetrexedradiation therapyPatients 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.
Std Tx + Pemetrexed and CetuximabcetuximabPatients 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.
Std Tx + Pemetrexed and Cetuximabpemetrexed disodiumPatients 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.
Std Tx + Pemetrexed and Cetuximabradiation therapyPatients 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.
Std Tx + Pemetrexedpemetrexed disodiumPatients 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.
Std Tx + PemetrexedcarboplatinPatients 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.
Std Tx + Pemetrexed and CetuximabcarboplatinPatients 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.
Primary Outcome Measures
NameTimeMethod
18 Month Survival18 months (from randomization)

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
NameTimeMethod
Failure-free SurvivalTime from randomization to failure (up to 4 years)

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 ResponseDuration of study until progression (up to 4 years)

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.

Trial Locations

Locations (71)

Arroyo Grande Community Hospital

🇺🇸

Arroyo Grande, California, United States

Eden Medical Center

🇺🇸

Castro Valley, California, United States

Saint Rose Hospital

🇺🇸

Hayward, California, United States

Rebecca and John Moores UCSD Cancer Center

🇺🇸

La Jolla, California, United States

Highland General Hospital

🇺🇸

Oakland, California, United States

Alta Bates Summit Medical Center - Summit Campus

🇺🇸

Oakland, California, United States

CCOP - Bay Area Tumor Institute

🇺🇸

Oakland, California, United States

Valley Care Medical Center

🇺🇸

Pleasanton, California, United States

Doctors Medical Center - San Pablo Campus

🇺🇸

San Pablo, California, United States

Bendheim Cancer Center at Greenwich Hospital

🇺🇸

Greenwich, Connecticut, United States

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Arroyo Grande Community Hospital
🇺🇸Arroyo Grande, California, United States

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