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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00117962
• Other study ID #: CALGB 30407
• Secondary ID: U10CA031946CDR00
• Status: Completed
• Phase: Phase 2
• First received: July 8, 2005
• Last updated: November 14, 2014
• Start date: September 2005
• Est. completion date: September 2012

Study information

• Verified date: November 2014
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: September 2012
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

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
• 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.

Locations

Country	Name	City	State
United States	Arroyo Grande Community Hospital	Arroyo Grande	California
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Mountainview Medical	Berlin	Vermont
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Eden Medical Center	Castro Valley	California
United States	Iowa Blood and Cancer Care	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	St. Luke's Hospital	Cedar Rapids	Iowa
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Roper St. Francis Cancer Center at Roper Hospital	Charleston	South Carolina
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York
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	McLeod Regional Medical Center	Florence	South Carolina
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center	Grand Island	Nebraska
United States	Bendheim Cancer Center at Greenwich Hospital	Greenwich	Connecticut
United States	Saint Rose Hospital	Hayward	California
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire
United States	St. Mary's Regional Cancer Center at St. Mary's Medical Center	Huntington	West Virginia
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	La Grange Memorial Hospital	La Grange	Illinois
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Lakes Region General Hospital	Laconia	New Hampshire
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Elliot Regional Cancer Center at Elliot Hospital	Manchester	New Hampshire
United States	Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County	Martinsville	Virginia
United States	Mount Sinai Medical Center	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Callahan Cancer Center at Great Plains Regional Medical Center	North Platte	Nebraska
United States	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Cancer Care Associates - Mercy Campus	Oklahoma City	Oklahoma
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center	Pinehurst	North Carolina
United States	Valley Care Medical Center	Pleasanton	California
United States	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri
United States	Doctors Medical Center - San Pablo Campus	San Pablo	California
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis	St Louis	Missouri
United States	Missouri Baptist Cancer Center	St. Louis	Missouri
United States	St. Anthony's Cancer Center	St. Louis	Missouri
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (4)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	Bristol-Myers Squibb, Eli Lilly and Company, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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-s — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Survival	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.	Time from randomization to death (up to 4 years)	No
Primary	18 Month Survival	Percentage of participants who were alive at 18 months. The 18 month survival, with 95% CI, was estimated using the Kaplan-Meier method.	18 months (from randomization)	No
Secondary	Failure-free Survival	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,	Time from randomization to failure (up to 4 years)	No
Secondary	Number of Participants With Overall Tumor Response	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.	Duration of study until progression (up to 4 years)	No