Clinical trial NCT00117962: Pemetrexed Disodium, Carboplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Stage III Non-Small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: 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
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Eli Lilly and Company
name: Bristol-Myers Squibb
First posted: 2005-07-11
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 18 Month Survival
timeFrame: 18 months (from randomization)
Secondary outcomes:
measure: Failure-free Survival
timeFrame: Time from randomization to failure (up to 4 years)
measure: Number of Participants With Overall Tumor Response
timeFrame: Duration of study until progression (up to 4 years)
Other outcomes:
measure: Overall Survival
timeFrame: Time from randomization to death (up to 4 years)
Locations:
city: Arroyo Grande
country: United States
facility: Arroyo Grande Community Hospital
state: California
city: Castro Valley
country: United States
facility: Eden Medical Center
state: California
city: Hayward
country: United States
facility: Saint Rose Hospital
state: California
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Oakland
country: United States
facility: Highland General Hospital
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Medical Center - Summit Campus
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Pleasanton
country: United States
facility: Valley Care Medical Center
state: California
city: San Pablo
country: United States
facility: Doctors Medical Center - San Pablo Campus
state: California
city: Greenwich
country: United States
facility: Bendheim Cancer Center at Greenwich Hospital
state: Connecticut
city: Lewes
country: United States
facility: Tunnell Cancer Center at Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute at Florida Hospital Orlando
state: Florida
city: Savannah
country: United States
facility: Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
state: Illinois
city: La Grange
country: United States
facility: La Grange Memorial Hospital
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Bettendorf
country: United States
facility: Hematology Oncology Associates of the Quad Cities
state: Iowa
city: Cedar Rapids
country: United States
facility: Iowa Blood and Cancer Care
state: Iowa
city: Cedar Rapids
country: United States
facility: St. Luke's Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Regional Cancer Center at Mercy Medical Center
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Bel Air
country: United States
facility: Upper Chesapeake Medical Center
state: Maryland
city: Elkton MD
country: United States
facility: Union Hospital Cancer Program at Union Hospital
state: Maryland
city: Fall River
country: United States
facility: Hudner Oncology Center at Saint Anne's Hospital - Fall River
state: Massachusetts
city: Chesterfield
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Saint Louis
country: United States
facility: Arch Medical Services, Incorporated at Center for Cancer Care and Research
state: Missouri
city: St Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis
state: Missouri
city: St. Louis
country: United States
facility: St. Anthony's Cancer Center
state: Missouri
city: St. Louis
country: United States
facility: Missouri Baptist Cancer Center
state: Missouri
city: Grand Island
country: United States
facility: Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center
state: Nebraska
city: North Platte
country: United States
facility: Callahan Cancer Center at Great Plains Regional Medical Center
state: Nebraska
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: CCOP - Nevada Cancer Research Foundation
state: Nevada
city: Hooksett
country: United States
facility: New Hampshire Oncology - Hematology, PA - Hooksett
state: New Hampshire
city: Laconia
country: United States
facility: Lakes Region General Hospital
state: New Hampshire
city: Manchester
country: United States
facility: Elliot Regional Cancer Center at Elliot Hospital
state: New Hampshire
city: Paterson
country: United States
facility: St. Joseph's Hospital and Medical Center
state: New Jersey
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: East Syracuse
country: United States
facility: CCOP - Hematology-Oncology Associates of Central New York
state: New York
city: Glens Falls
country: United States
facility: Charles R. Wood Cancer Center at Glens Falls Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Asheville
country: United States
facility: Mission Hospitals - Memorial Campus
state: North Carolina
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Hendersonville
country: United States
facility: Pardee Memorial Hospital
state: North Carolina
city: Kinston
country: United States
facility: Kinston Medical Specialists
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Oklahoma City
country: United States
facility: Cancer Care Associates - Mercy Campus
state: Oklahoma
city: Providence
country: United States
facility: Rhode Island Hospital Comprehensive Cancer Center
state: Rhode Island
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Roper St. Francis Cancer Center at Roper Hospital
state: South Carolina
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Kingsport
country: United States
facility: Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
state: Tennessee
city: Berlin
country: United States
facility: Mountainview Medical
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Martinsville
country: United States
facility: Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County
state: Virginia
city: Norton
country: United States
facility: Southwest Virginia Regional Cancer Center at Wellmonth Health
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Huntington
country: United States
facility: St. Mary's Regional Cancer Center at St. Mary's Medical Center
state: West Virginia
Study officials:
affiliation: Washington University School of Medicine
name: Ramaswamy Govindan, MD
role: STUDY_CHAIR
References:
citation: 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.