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

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

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.

Study Overview

• Status: Terminated
• Conditions: Recurrent Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Adenocarcinoma of the Lung; Large Cell Lung Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: crizotinib; Drug: pemetrexed disodium

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center - Anschutz Cancer Pavilion
    • Colorado Springs, Colorado, United States, 80909
      • Memorial Hospital Colorado Springs
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Medical Center
    • Post Falls, Idaho, United States, 83854
      • Kootenai Cancer Center
    • Sandpoint, Idaho, United States, 83864
      • Kootenai Cancer
  • Illinois
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
  • Indiana
    • Richmond, Indiana, United States, 47374
      • Reid Health
  • Iowa
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Council Bluffs, Iowa, United States, 51503
      • Alegent Health Mercy Hospital
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67905
      • Cancer Center of Kansas-Liberal
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Flaget Memorial Hospital
    • Corbin, Kentucky, United States, 40701
      • Commonwealth Cancer Center-Corbin
    • Crestview Hills, Kentucky, United States, 41017
      • Oncology Hematology Care Inc-Crestview
    • Lexington, Kentucky, United States, 40504
      • Saint Joseph Radiation Oncology Resource Center
    • Lexington, Kentucky, United States, 40509
      • Saint Joseph Hospital East
    • Louisville, Kentucky, United States, 40202
      • Jewish Hospital
    • Louisville, Kentucky, United States, 40215
      • Saints Mary and Elizabeth Hospital
    • Louisville, Kentucky, United States, 40245
      • Jewish Hospital Medical Center Northeast
    • Shepherdsville, Kentucky, United States, 40165
      • Jewish Hospital Medical Center South
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital-Dearborn
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States, 48334
      • Weisberg Cancer Treatment Center
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center-Carrie J Babb Cancer Center
    • Branson, Missouri, United States, 65616
      • CoxHealth Cancer Center
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital-Joplin
    • Rolla, Missouri, United States, 65401
      • Phelps County Regional Medical Center
    • Rolla, Missouri, United States, 65401
      • Saint John's Clinic-Rolla-Cancer and Hematology
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59101
      • Montana Cancer Consortium NCORP
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59801
      • Community Medical Hospital
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis
    • Kearney, Nebraska, United States, 68847
      • CHI Health Good Samaritan
    • Kearney, Nebraska, United States, 68845
      • Heartland Hematology and Oncology
    • Lincoln, Nebraska, United States, 68506
      • Nebraska Hematology and Oncology
    • Lincoln, Nebraska, United States, 68510
      • Nebraska Cancer Research Center
    • Lincoln, Nebraska, United States, 68510
      • Saint Elizabeth Regional Medical Center
    • Lincoln, Nebraska, United States, 68510
      • Southeast Nebraska Cancer Center
    • Norfolk, Nebraska, United States, 68701
      • Faith Regional Medical Offices West
    • North Platte, Nebraska, United States, 69103
      • Great Plains Regional Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
    • Omaha, Nebraska, United States, 68130
      • Alegent Health Lakeside Hospital
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68106
      • Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West PC
    • Omaha, Nebraska, United States, 68122
      • Hemotology and Oncology Consultants PC
    • Omaha, Nebraska, United States, 68124
      • Oncology Hematology West
    • Papillion, Nebraska, United States, 68046
      • Midlands Community Hospital
    • Scottsbluff, Nebraska, United States, 69361
      • Regional West Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
    • Manchester, New Hampshire, United States, 03102
      • Norris Cotton Cancer Center-Manchester
    • Nashua, New Hampshire, United States, 03063
      • Norris Cotton Cancer Center-Nashua
  • New York
    • Middletown, New York, United States, 10940
      • Orange Regional Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Hematology-Oncology Associates
    • Hendersonville, North Carolina, United States, 28792
      • Park Ridge Hospital Breast Health Center
  • Ohio
    • Belpre, Ohio, United States, 45714
      • Strecker Cancer Center-Belpre
    • Centerville, Ohio, United States, 45459
      • Miami Valley Hospital South
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital - Cincinnati
    • Cincinnati, Ohio, United States, 45242
      • Bethesda North Hospital
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc-Blue Ash
    • Cincinnati, Ohio, United States, 45202
      • Oncology Hematology Care Inc-Eden Park
    • Cincinnati, Ohio, United States, 45211
      • Oncology Hematology Care Inc-Mercy West
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Care Inc-Kenwood
    • Cincinnati, Ohio, United States, 45230
      • Oncology Hematology Care Inc - Anderson
    • Cincinnati, Ohio, United States, 45247
      • TriHealth Cancer Institute-Westside
    • Cincinnati, Ohio, United States, 45255
      • TriHealth Cancer Institute-Anderson
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43219
      • The Mark H Zangmeister Center
    • Columbus, Ohio, United States, 43214
      • Columbus Oncology and Hematology Associates Inc
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Columbus, Ohio, United States, 43215
      • Columbus NCI Community Oncology Research Program
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Delaware, Ohio, United States, 43015
      • Delaware Health Center-Grady Cancer Center
    • Delaware, Ohio, United States, 43015
      • Delaware Radiation Oncology
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Fairfield, Ohio, United States, 45014
      • Oncology Hematology Care Inc-Healthplex
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Newark, Ohio, United States, 43055
      • Newark Radiation Oncology
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Springfield, Ohio, United States, 45504
      • Springfield Regional Cancer Center
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Wright-Patterson Air Force Base, Ohio, United States, 45433-5529
      • Wright-Patterson Medical Center
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • SWOG
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Cancer Center
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Memorial Hospital
    • Hixson, Tennessee, United States, 37343
      • Pulmonary Medicine Center of Chattanooga-Hixson
    • Ooltewah, Tennessee, United States, 37363
      • Memorial GYN Plus
  • Washington
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Bremerton, Washington, United States, 98310
      • Harrison Medical Center
    • Burien, Washington, United States, 98166
      • Highline Medical Center-Main Campus
    • Enumclaw, Washington, United States, 98022
      • Saint Elizabeth Hospital
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Lakewood, Washington, United States, 98499
      • Saint Clare Hospital
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties PLLC
    • Tacoma, Washington, United States, 98405
      • Franciscan Research Center-Northwest Medical Plaza
  • Wyoming
    • Cody, Wyoming, United States, 82414
      • Big Horn Basin Cancer Center
    • Cody, Wyoming, United States, 82414
      • Billings Clinic-Cody
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (crizotinib, pemetrexed disodium); Patients receive crizotinib PO BID on days 1-21 and pemetrexed disodium IV over 10 minutes on day 1.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: crizotinib; Given PO; Other Names: MET Tyrosine Kinase Inhibitor PF-02341066; PF-02341066; c-met/hepatocyte growth factor receptor tyrosine kinase inhibitor PF-02341066; c-met/HGFR tyrosine kinase inhibitor PF-02341066; Drug: pemetrexed disodium; Given IV; Other Names: ALIMTA; LY231514; MTA
Experimental: Arm II (pemetrexed disodium); 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.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: pemetrexed disodium; Given IV; Other Names: ALIMTA; LY231514; MTA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David Camidge, Southwest Oncology Group

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: May 7, 2014
• First Submitted That Met QC Criteria: May 7, 2014
• First Posted (Estimate): May 9, 2014

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 19, 2020
• Last Verified: February 1, 2020

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Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Pemetrexed; Crizotinib
• Other Study ID Numbers: S1300 (Other Identifier: CTEP); U10CA032102 (U.S. NIH Grant/Contract); U10CA180888 (U.S. NIH Grant/Contract); NCI-2014-00685 (Registry Identifier: CTRP (Clinical Trial Reporting Program))