S1300: Pemetrexed Disodium With or Without Crizotinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer That Has Progressed After Crizotinib

Stage IV Non-small Cell Lung Cancer Clinical Trial

Official title:

S1300: A Randomized, Phase II Trial of Crizotinib Plus Pemetrexed Versus Pemetrexed Monotherapy in ALK-Positive Non-squamous NSCLC Patients Who Have Progressed Systemically After Previous Clinical Benefit From Crizotinib Monotherapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02134912
• Other study ID #: S1300
• Secondary ID: NCI-2014-00685S1
• Status: Terminated
• Phase: Phase 2
• Start date: August 2014
• Est. completion date: September 2016

Study information

• Verified date: February 2020
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies how well pemetrexed disodium with or without crizotinib works in treating patients with stage IV non-small cell lung cancer that has progressed after crizotinib. Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving pemetrexed disodium is more effective with or without crizotinib in treating patients with non-small cell lung cancer that has progressed after crizotinib.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of the combination of crizotinib and pemetrexed (pemetrexed disodium) compared to pemetrexed monotherapy as measured by progression-free survival (PFS) in anaplastic lymphoma kinase (ALK)+ non-squamous non-small cell lung cancer (NSCLC) patients who achieved clinical benefit with crizotinib monotherapy and subsequently progressed systemically.

SECONDARY OBJECTIVES:

I. To compare the response rate (confirmed and unconfirmed, complete and partial responses) in patients randomized to receive pemetrexed monotherapy to historical data.

II. To assess overall survival in both arms. III. To evaluate the patterns of failure (central nervous system [CNS], extra-CNS) of the combination of crizotinib and pemetrexed and of pemetrexed monotherapy in ALK+ non-squamous NSCLC after progression on crizotinib.

IV. To evaluate the frequency and severity of toxicities resulting from the administration of crizotinib and pemetrexed compared to pemetrexed monotherapy.

V. To evaluate PFS and the response rate in patients treated with crizotinib following progression on the pemetrexed monotherapy arm.

TERTIARY OBJECTIVES:

I. To compare progression-free survival (PFS) and response rates (RR) between ALK dominant and ALK non-dominant patients in the entire study population and within each treatment arm.

II. To evaluate if the magnitude of difference in these outcomes between ALK dominant and ALK non-dominant patients varies by treatment arm.

III. To assess blood biomarkers of sensitivity and resistance to crizotinib and pemetrexed in an exploratory manner. The blood biomarkers include cell free circulating deoxyribonucleic acid (DNA), micro ribonucleic acid (microRNA) before treatment, during treatment (after 2 cycles) and at treatment progression.

IV. To assess pharmacogenomic factors in peripheral blood that might affect the drug level and treatment outcomes in an exploratory manner.

V. To assess proteomic/immunologic parameters that might affect the treatment outcomes in an exploratory manner.

VI. To evaluate the frequency of individual mechanisms of resistance (copy number gain [CNG], mutation, alternate oncogene).

VII. To identify alternative driver mechanisms in ALK fluorescence in situ hybridization positive (FISH+) otherwise unknown.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21 and pemetrexed disodium intravenously (IV) over 10 minutes on day 1.

ARM II: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Upon disease progression or symptomatic deterioration, patients may crossover to Arm I.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have histologically or cytologically proven primary non-squamous non-small cell lung cancer (adenocarcinoma, large cell carcinoma, adenocarcinoma in situ, mixed histology with < 50% squamous or unspecified); patients with tumors having squamous cell components >= 50% are not eligible; disease must be stage IV

• Patients must have documented ALK positivity at the time of initial crizotinib monotherapy using the Vysis Break-Apart FISH assay (or other Food and Drug Administration [FDA]-approved diagnostic test); samples are deemed to be FISH-positive if greater than or equal to 15% of scored tumor cells had split ALK 5' and 3' probe signals or had isolated 3' signal; FISH status must be documented on the Onstudy Form and a copy of the pathology report from the Vysis Break-Apart FISH assay (or other FDA-approved diagnostic test) must be submitted

• Prior to registration, patients must have achieved clinical benefit with crizotinib monotherapy and subsequently have systemically progressed; clinical benefit is defined as having stable disease on crizotinib monotherapy for at least 90 days or achieving a confirmed partial or complete response; systemic progression is defined as progressive disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, excluding progression based on brain/CNS metastases alone

• Patients must have received crizotinib monotherapy at 250 mg BID on a continuous dosing schedule for at least 90 days; patients must be planning to start treatment at least three days, but no more than 30 days after discontinuing crizotinib monotherapy; patients who were not able to tolerate 250 mg BID of crizotinib are not eligible for this study

• Patients must be pemetrexed-naïve; patients may have received any number of prior chemotherapy or molecularly targeted agents; if crizotinib was used in the 1st line setting then chemotherapy naive patients are also eligible; if patient received crizotinib in combination with chemotherapy, prior chemotherapy must have been discontinued at least 14 days prior to registration and all adverse events must have resolved to =< grade 1

• Patients must have measurable disease per RECIST documented by computed tomography (CT) or magnetic resonance imaging (MRI); the CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality; measurable disease must be assessed within 28 days prior to registration; pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease; non-measurable disease must be assessed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form RECIST 1.1

• Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to registration; patient must not have brain metastases unless: (1) metastases have been treated and have remained controlled for at least 14 days following treatment or was not treated, but is asymptomatic, AND (2) patient has no residual neurological dysfunction off corticosteroids or anti-convulsants for at least 14 days

• Patients may have received palliative radiotherapy to non-target lesions within 14 days prior to registration provided all radiotherapy related toxicities have resolved to =< grade 1 prior to registration; patients must not have received any major surgery within 28 days prior to registration

• Patients must not have had any prior exposure to heat shock protein (HSP)90 inhibitors (such as IPI-504 or ganetespib) or non-crizotinib ALK inhibitors (such as AP26113 or LDK378)

• Patients must be offered participation in the translational medicine studies; additionally if patient has biopsy accessible disease they must be offered participation in the translational medicine studies

• Absolute neutrophil count (ANC) >= 1,500/ul

• Platelet count >= 100,000/ul

• Hemoglobin >= 9 g/dL

• Serum bilirubin =< 2 X institutional upper limit of normal (IULN)

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x IULN

• Estimated (calculated) or measured glomerular filtration rate >= 45 mL/min (or 45 mL/min/1.73 m^2); creatinine (mg/dl) used in calculation (Cockroft-Gault) must be obtained within 28 days prior to registration

• Male patients must have free and total testosterone level obtained within 28 days prior to registration

• Pre-study history and physical must be obtained with 28 days prior to registration

• Patients must have Zubrod performance status 0-2 within 28 days prior to registration

• Patients must be able to swallow capsules

• Patients must have corrected QT (QTC) interval =< 480 msec on electrocardiogram (EKG) at baseline; patient with congenital long QT syndrome are not eligible

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years

• Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

• REGULATORY CRITERIA: Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• REGULATORY CRITERIA: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

• CROSSOVER (STEP 2) REGISTRATION: Patients must have progressed systemically on Arm 2 of this study (pemetrexed monotherapy)

• CROSSOVER (STEP 2) REGISTRATION: Patients must be registered to crossover (Step 2) within 30 days of discontinuing treatment on Arm 2 of this study

• CROSSOVER (STEP 2) REGISTRATION: ANC >= 1,500/ul

• CROSSOVER (STEP 2) REGISTRATION: Platelet count >= 100,000/ul

• CROSSOVER (STEP 2) REGISTRATION: Serum bilirubin =< 2 X IULN

• CROSSOVER (STEP 2) REGISTRATION: SGOT (AST) or SGPT (ALT) =< 2.5 x IULN

• CROSSOVER (STEP 2) REGISTRATION: estimated (calculated) or measured glomerular filtration rate >= 45 mL/min (or 45 mL/min/1.73 m^2) within 28 days prior to registration; creatinine (mg/dl) used in calculation (Cockroft-Gault) must be obtained within 28 days prior to registration

• CROSSOVER (STEP 2) REGISTRATION: male patients must have free and total testosterone level obtained within 28 days prior to Crossover (Step 2) Registration

• CROSSOVER (STEP 2) REGISTRATION: patients must have Zubrod performance status 0-2 within 28 days prior to Crossover (Step 2) Registration

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Adenocarcinoma of the Lung
• Carcinoma, Non-Small-Cell Lung
• Large Cell Lung Cancer
• Lung Neoplasms
• Recurrent Non-small Cell Lung Cancer
• Stage IV Non-small Cell Lung Cancer

Intervention

Drug:
• crizotinib
Given PO
• pemetrexed disodium
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Asheville Hematology-Oncology Associates	Asheville	North Carolina
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Central Care Cancer Center-Carrie J Babb Cancer Center	Bolivar	Missouri
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	CoxHealth Cancer Center	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc - Anderson	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Big Horn Basin Cancer Center	Cody	Wyoming
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Medical Center	Coeur d'Alene	Idaho
United States	Memorial Hospital Colorado Springs	Colorado Springs	Colorado
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Beaumont Hospital-Dearborn	Dearborn	Michigan
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Saint Francis Hospital	Federal Way	Washington
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Park Ridge Hospital Breast Health Center	Hendersonville	North Carolina
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital-Joplin	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	Kettering Medical Center	Kettering	Ohio
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Saint Clare Hospital	Lakewood	Washington
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Nebraska Cancer Research Center	Lincoln	Nebraska
United States	Nebraska Hematology and Oncology	Lincoln	Nebraska
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Southeast Nebraska Cancer Center	Lincoln	Nebraska
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Jewish Hospital	Louisville	Kentucky
United States	Jewish Hospital Medical Center Northeast	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	Norris Cotton Cancer Center-Manchester	Manchester	New Hampshire
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Orange Regional Medical Center	Middletown	New York
United States	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Norris Cotton Cancer Center-Nashua	Nashua	New Hampshire
United States	Licking Memorial Hospital	Newark	Ohio
United States	Newark Radiation Oncology	Newark	Ohio
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Faith Regional Medical Offices West	Norfolk	Nebraska
United States	Great Plains Regional Medical Center	North Platte	Nebraska
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Hemotology and Oncology Consultants PC	Omaha	Nebraska
United States	Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Oncology Hematology West	Omaha	Nebraska
United States	Oncology Hematology West PC	Omaha	Nebraska
United States	Memorial GYN Plus	Ooltewah	Tennessee
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	SWOG	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Reid Health	Richmond	Indiana
United States	Mayo Clinic	Rochester	Minnesota
United States	Phelps County Regional Medical Center	Rolla	Missouri
United States	Saint John's Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Kootenai Cancer	Sandpoint	Idaho
United States	Regional West Medical Center	Scottsbluff	Nebraska
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Flower Hospital	Sylvania	Ohio
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Upper Valley Medical Center	Troy	Ohio
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS Between Patients Randomized to Receive Pemetrexed Disodium Monotherapy Versus Crizotinib and Pemetrexed Disodium Combination Therapy	A stratified log-rank test at the 0.10 level will be used to test the primary hypothesis comparing the two treatment arms.	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years
Secondary	Incidence of Adverse Events of Crizotinib in Combination With Pemetrexed Disodium, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0	Comparisons of toxicities rates will be done using a Fisher's exact or chi-squared test of independence, when appropriate using 10% as the significance threshold. Within each treatment arm, any toxicity with at least 5% prevalence has at least a 95% chance of being observed.	Up to 3 years
Secondary	Response Rate (Confirmed and Unconfirmed) With Pemetrexed Disodium Monotherapy	Comparisons of response rates will be done using a chi-square test of independence using 10% as the significance threshold. Within each treatment arm, response rates can be estimated to within 13% (with 95% confidence).	Up to 3 years
Secondary	Response Rates (Confirmed and Unconfirmed) of Crizotinib With Pemetrexed Disodium	Comparisons of response rates will be done using a chi-square test of independence using 10% as the significance threshold. Within each treatment arm, response rates can be estimated to within 13% (with 95% confidence).	Up to 3 years
Secondary	Patterns of Failure	Defined as CNS-only, extra-CNS, and both CNS and extra-CNS progression between the treatment arms. Evaluated within each treatment arm using cumulative incidence curves.	Up to 3 years
Secondary	Overall Survival	Differences in OS by treatment arm will be evaluated using a 1-sided log-rank test with significant level of 10%.	Up to 3 years