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

NCT ID: NCT00117962

Last Updated: 2016-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2012-09-30

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.

Conditions

Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

AUC = 5 q 21 days for 4 cycles

pemetrexed disodium

Intervention Type: DRUG

500 mg/sq m IV q 21 days during chemoradiation and consolidation chemotherapy phases

radiation therapy

Intervention Type: RADIATION

Thoracic radiotherapy: 70 Gy for 7 weeks beginning on Day 1.

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.

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

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.

carboplatin

Intervention Type: DRUG

AUC = 5 q 21 days for 4 cycles

pemetrexed disodium

Intervention Type: DRUG

500 mg/sq m IV q 21 days during chemoradiation and consolidation chemotherapy phases

radiation therapy

Intervention Type: RADIATION

Thoracic radiotherapy: 70 Gy for 7 weeks beginning on Day 1.

Interventions

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.

Intervention Type: BIOLOGICAL

carboplatin

AUC = 5 q 21 days for 4 cycles

Intervention Type: DRUG

pemetrexed disodium

500 mg/sq m IV q 21 days during chemoradiation and consolidation chemotherapy phases

Intervention Type: DRUG

radiation therapy

Thoracic radiotherapy: 70 Gy for 7 weeks beginning on Day 1.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ramaswamy Govindan, MD

Role: STUDY_CHAIR

Washington University School of Medicine

Locations

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

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, United States

Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Louis A. Weiss Memorial Hospital

Chicago, Illinois, United States

La Grange Memorial Hospital

La Grange, Illinois, United States

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States

Hematology Oncology Associates of the Quad Cities

Bettendorf, Iowa, United States

Iowa Blood and Cancer Care

Cedar Rapids, Iowa, United States

St. Luke's Hospital

Cedar Rapids, Iowa, United States

Mercy Regional Cancer Center at Mercy Medical Center

Cedar Rapids, Iowa, United States

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Upper Chesapeake Medical Center

Bel Air, Maryland, United States

Union Hospital Cancer Program at Union Hospital

Elkton MD, Maryland, United States

Hudner Oncology Center at Saint Anne's Hospital - Fall River

Fall River, Massachusetts, United States

Saint Luke's Hospital

Chesterfield, Missouri, United States

Missouri Cancer Associates

Columbia, Missouri, United States

Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis

St Louis, Missouri, United States

St. Anthony's Cancer Center

St Louis, Missouri, United States

Missouri Baptist Cancer Center

St Louis, Missouri, United States

Arch Medical Services, Incorporated at Center for Cancer Care and Research

St Louis, Missouri, United States

Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center

Grand Island, Nebraska, United States

Callahan Cancer Center at Great Plains Regional Medical Center

North Platte, Nebraska, United States

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

New Hampshire Oncology - Hematology, PA - Hooksett

Hooksett, New Hampshire, United States

Lakes Region General Hospital

Laconia, New Hampshire, United States

Elliot Regional Cancer Center at Elliot Hospital

Manchester, New Hampshire, United States

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, United States

CCOP - Hematology-Oncology Associates of Central New York

East Syracuse, New York, United States

Charles R. Wood Cancer Center at Glens Falls Hospital

Glens Falls, New York, United States

Mount Sinai Medical Center

New York, New York, United States

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Veterans Affairs Medical Center - Syracuse

Syracuse, New York, United States

Mission Hospitals - Memorial Campus

Asheville, North Carolina, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Wayne Memorial Hospital, Incorporated

Goldsboro, North Carolina, United States

Pardee Memorial Hospital

Hendersonville, North Carolina, United States

Kinston Medical Specialists

Kinston, North Carolina, United States

FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center

Pinehurst, North Carolina, United States

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, United States

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Cancer Care Associates - Mercy Campus

Oklahoma City, Oklahoma, United States

Rhode Island Hospital Comprehensive Cancer Center

Providence, Rhode Island, United States

Miriam Hospital

Providence, Rhode Island, United States

Roper St. Francis Cancer Center at Roper Hospital

Charleston, South Carolina, United States

McLeod Regional Medical Center

Florence, South Carolina, United States

Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center

Kingsport, Tennessee, United States

Mountainview Medical

Berlin Corners, Vermont, United States

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, United States

Danville Regional Medical Center

Danville, Virginia, United States

Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County

Martinsville, Virginia, United States

Southwest Virginia Regional Cancer Center at Wellmonth Health

Norton, Virginia, United States

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

St. Mary's Regional Cancer Center at St. Mary's Medical Center

Huntington, West Virginia, United States

Countries

United States

References

Govindan R, Bogart J, Stinchcombe T, Wang X, Hodgson L, Kratzke R, Garst J, Brotherton T, Vokes EE. Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: Cancer and Leukemia Group B trial 30407. J Clin Oncol. 2011 Aug 10;29(23):3120-5. doi: 10.1200/JCO.2010.33.4979. Epub 2011 Jul 11.

Reference Type: RESULT

PMID: 21747084 (View on PubMed)

Other Identifiers

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000434616

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB 30407

Identifier Type: -

Identifier Source: org_study_id