Erlotinib Hydrochloride and Cabozantinib-s-Malate Alone or in Combination as Second or Third Line Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT01708954
Collaborator
(none)
125
369
4
0.3

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well giving erlotinib hydrochloride and cabozantinib-s-malate alone or in combination works as second or third line therapy in treating patient with stage IV non-small cell lung cancer. Erlotinib hydrochloride and cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving erlotinib hydrochloride together with cabozantinib-s-malate is more effective than erlotinib hydrochloride or cabozantinib-s-malate alone in treating non-small cell lung cancer.

Condition or Disease Intervention/Treatment Phase
  • Drug: Cabozantinib S-malate
  • Drug: Erlotinib Hydrochloride
  • Other: Laboratory Biomarker Analysis
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To compare the progression-free survival (PFS) associated with patients treated with erlotinib (erlotinib hydrochloride) versus (vs) erlotinib plus cabozantinib (cabozantinib-s-malate).

  2. To compare the PFS associated with patients treated with erlotinib vs cabozantinib.

SECONDARY OBJECTIVES:
  1. To evaluate overall survival in the three treatment arms. II. To evaluate best objective response rate in the three treatment arms. III. To define the toxicity associated with each regimen. IV. To conduct correlative science studies that will help to select predictive biomarkers of response to therapy, including mesenchymal-epidermal transition (MET) expression and potentially other tissue biomarkers, plasma biomarkers, and bone scans.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM A (erlotinib): Patients receive erlotinib orally (PO) daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B (cabozantinib): Patients receive cabozantinib PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM C (erlotinib+cabozantinib): Patients receive erlotinib as patients in Arm A and cabozantinib as patients in Arm B. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM Z: Patients achieving disease progression in Arm A or Arm B may receive erlotinib and cabozantinib as patients in Arm C. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
125 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II Trial of Erlotinib, Cabozantinib, or Erlotinib Plus Cabozantinib as 2nd or 3rd Line Therapy in Patients With EGFR Wild-Type NSCLC
Actual Study Start Date :
Feb 13, 2013
Actual Primary Completion Date :
Aug 14, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A (erlotinib)

Patients receive erlotinib PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Erlotinib Hydrochloride
Given PO
Other Names:
  • Cp-358,774
  • OSI-774
  • Tarceva
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Experimental: Arm B (cabozantinib)

    Patients receive cabozantinib PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: Cabozantinib S-malate
    Given PO
    Other Names:
  • BMS-907351
  • Cabometyx
  • Cometriq
  • XL-184
  • XL184
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Experimental: Arm C (erlotinib+cabozantinib)

    Patients receive erlotinib as patients in Arm A and cabozantinib as patients in Arm B. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: Cabozantinib S-malate
    Given PO
    Other Names:
  • BMS-907351
  • Cabometyx
  • Cometriq
  • XL-184
  • XL184
  • Drug: Erlotinib Hydrochloride
    Given PO
    Other Names:
  • Cp-358,774
  • OSI-774
  • Tarceva
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Experimental: Arm Z (erlotinib+cabozantinib; step II)

    Patients achieving disease progression in Arm A or Arm B may receive erlotinib and cabozantinib as patients in Arm C. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: Cabozantinib S-malate
    Given PO
    Other Names:
  • BMS-907351
  • Cabometyx
  • Cometriq
  • XL-184
  • XL184
  • Drug: Erlotinib Hydrochloride
    Given PO
    Other Names:
  • Cp-358,774
  • OSI-774
  • Tarceva
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) [Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years]

      PFS is defined as the time from randomization to documented disease progression or death from any cause, whichever occurred first. Patients who had not experienced an event of interest by the time of analysis were censored at the date of last disease assessment.

    Secondary Outcome Measures

    1. Overall Survival (OS) [Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years]

      OS is defined as the time from randomization to death from any cause or date of last known alive.

    2. Proportion of Patients With Objective Response [Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years]

      Objective response is defined as complete response (CR) or partial response (PR) evaluated using RECIST v 1.1. CR is defined as disappearance of all lesions and any pathological lymph nodes must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions and persistence of one or more non-target lesion(s).

    3. Proportion of Patients With MET Positivity [Assessed at baseline]

      Submission of archival tissue for central MET IHC testing was required for this study, and total MET IHC testing was conducted at the Brigham and Women's Hospital using the c-Met clone CVD13 (arabbit polyclonal). Membranous and cytoplasmic staining were individually scored, and positivity was declared if MET was expressed in either the membrane or cytoplasm.

    4. Proportion of Patients With Worst Grade Toxicities of Grade 3 or Higher [Assessed every 4 weeks while on treatment and for 30 days after the end of treatment]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Criteria:
    • Tumor with a sensitizing mutation in epidermal growth factor receptor (EGFR), defined as follows:

    • EGFR mutation testing of tumor has been performed and did not demonstrate an EGFR tyrosine kinase inhibitor sensitizing mutation; at minimum, testing for EGFR exon 19 deletion and exon 21 L858R mutations must have been included; OR

    • EGFR mutation testing has been attempted and is inconclusive (for example, due to lack of sufficient deoxyribonucleic acid [DNA] yield); OR

    • EGFR mutation status is unknown but tumor is positive for at least one alternative driver mutation, i.e: Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, v-raf murine sarcoma viral oncogene homolog B (BRAF) mutation, human epidermal growth factor receptor 2 (HER2) mutation, ret proto-oncogene (RET) rearrangement/fusion, or one not listed following approval by the study chair prior to registration

    Inclusion Criteria:
    • INCLUSION CRITERIA STEP 1:

    • Cytologically or histologically confirmed non-small cell lung carcinoma (NSCLC)

    • Predominant non-squamous histology (patients with NSCLC not otherwise specified [NOS] are eligible); mixed tumors will be categorized by the predominant cell type; if small cell elements are present the patient is ineligible

    • Stage IV disease (includes M1a, M1b, or recurrent disease), according to the 7th edition of the lung cancer TNM classification system

    • Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria; baseline measurements and evaluation of all sites of disease must be obtained within 4 weeks prior to registration

    • Prior to registration, the investigator/site must confirm that sufficient pathology material representative of patient's cancer is available for submission for MET immunohistochemical (IHC) testing

    • Patients must have received one or two lines of prior chemotherapy (first line platinum-doublet based chemotherapy plus switch maintenance chemotherapy counts as one line of therapy); prior adjuvant chemotherapy for early stage disease does not count as one line of therapy if 12 months or greater elapsed between completion of adjuvant therapy and initiation of first-line systemic therapy; if less than 12 months elapsed, adjuvant chemotherapy counts as one line of therapy

    • Any prior chemotherapy (based on administration schedule) must have been completed in greater than or equal to the time frames specified in the protocol

    • Patients must have discontinued treatment with any other type of investigational agent

    = 4 weeks prior to registration

    • Patients must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 =< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)

    • Patients with no known brain metastasis at baseline must have baseline brain imaging within 12 weeks prior to study registration not demonstrating brain metastases; patients with brain metastases at baseline must have baseline brain imagining within 4 weeks prior to study registration and meet all of the specific criteria for brain mets listed in the protocol

    • Radiation related toxicities must have resolved to =< grade 1 prior to registration

    • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-2

    • Patients must have an anticipated life expectancy greater than 3 months

    • Acceptable bone marrow, renal and hepatic function within 2 weeks prior to registration as defined in the protocol

    • Patients must have corrected QT interval calculated by the Fridericia formula (QTcF) =< 500 ms within 28 days before registration

    • Patients must be able to swallow tablets

    • INCLUSION CRITERIA STEP 2:

    • Patients must have met all eligibility requirements for Step 1 at time of registration to Step 1 to be eligible for Step 2

    • Patients must have radiographic progressive disease per RECIST v1.1 criteria after >= 2 courses of therapy on Arm A or Arm B

    • Patients must be registered to Step 2 within 4 weeks of the last dose of treatment administration from Step 1

    • Patients must have an ECOG performance status between 0-2

    • Patients must have recovered to baseline (pre-Step 1) or CTCAE version 4.0 <= grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs

    Exclusion Criteria:
    • EXCLUSION CRITERIA STEP 1:

    • Patients without sufficient pathology material representative of the patient's cancer (tumor block or 10 unstained slides)

    • Prior erlotinib, other EGFR tyrosine kinase inhibitor therapy, vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor therapy, Met tyrosine kinase inhibitor therapy, or Met monoclonal antibody (MetMAb); prior antibody therapy such as bevacizumab or cetuximab is allowed with a washout period depending on dosing interval and investigational nature

    • Prior radiation therapy to the thoracic cavity, abdomen, or pelvis within 3 months prior to registration, to bone or brain metastasis within 14 days prior to registration, or to any other site within 28 days prior to registration

    • History of the following: Clinically-significant gastrointestinal (GI) bleeding within 6 months prior to registration; Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months prior to registration; Any other signs indicative of pulmonary hemorrhage within 3 months prior to registration

    • Radiographic or other evidence of the following within 28 days prior to registration: • Tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor; Cavitating pulmonary lesion(s); Tumor in contact with, invading or encasing any major blood vessels

    • Psychiatric illness/social situations that would limit compliance with study requirements

    • History of major thrombotic events (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 6 months prior to registration

    • Concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, low molecular weight heparin (LMWH), thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). (low dose aspirin [=< 81 mg/day] and prophylactic LMWH are permitted)

    • Concomitant treatment of strong cytochrome P450 3A4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort)

    • Cardiovascular disorders including: Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening;

    • Concurrent uncontrolled hypertension; Any history of congenital long QT syndrome; Any of the following within 6 months prior to registration:

    • Unstable angina pectoris

    • Clinically-significant cardiac arrhythmias

    • Stroke (including transient ischemic attack [TIA], or other ischemic event)

    • Myocardial infarction

    • GI disorders particularly those associated with a high risk of perforation or fistula formation specified in the protocol

    • Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months prior to registration

    • Uncontrolled, significant, intercurrent or recent illness

    • Prior malignancy within 2 years prior to registration which required systemic treatment or is currently active

    • Pregnant or breast-feeding

    • Patients with known human immunodeficiency virus (HIV) disease taking antiretroviral therapy

    • Known chronic active hepatitis B

    • EXCLUSION CRITERIA (STEP 2):

    • Intervening anticancer treatment or major surgical procedure(s) between Step 1 and Step 2, except palliative radiation to the bone finishing >= 2 weeks prior to registration to Step 2

    • Central nervous system (CNS) progression; patients with stable CNS disease are allowed

    • Intercurrent illness or disease complication that the investigator believes would limit the ability to safely tolerate the combination of erlotinib and cabozantinib

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic in Arizona Scottsdale Arizona United States 85259
    2 Memorial Medical Center Modesto California United States 95355
    3 Community Hospital of Monterey Peninsula Monterey California United States 93940
    4 Stanford Cancer Institute Palo Alto Palo Alto California United States 94304
    5 VA Palo Alto Health Care System Palo Alto California United States 94304
    6 Eisenhower Medical Center Rancho Mirage California United States 92270
    7 The Medical Center of Aurora Aurora Colorado United States 80012
    8 Boulder Community Hospital Boulder Colorado United States 80301
    9 Rocky Mountain Cancer Centers-Boulder Boulder Colorado United States 80304
    10 Penrose-Saint Francis Healthcare Colorado Springs Colorado United States 80907
    11 Rocky Mountain Cancer Centers-Penrose Colorado Springs Colorado United States 80907
    12 Porter Adventist Hospital Denver Colorado United States 80210
    13 Colorado Blood Cancer Institute Denver Colorado United States 80218
    14 Presbyterian - Saint Lukes Medical Center - Health One Denver Colorado United States 80218
    15 Rocky Mountain Cancer Centers-Midtown Denver Colorado United States 80218
    16 SCL Health Saint Joseph Hospital Denver Colorado United States 80218
    17 Rocky Mountain Cancer Centers-Rose Denver Colorado United States 80220
    18 Rose Medical Center Denver Colorado United States 80220
    19 Western States Cancer Research NCORP Denver Colorado United States 80222
    20 Mercy Medical Center Durango Colorado United States 81301
    21 Mountain Blue Cancer Care Center - Swedish Englewood Colorado United States 80113
    22 Swedish Medical Center Englewood Colorado United States 80113
    23 Mountain Blue Cancer Care Center Golden Colorado United States 80401
    24 North Colorado Medical Center Greeley Colorado United States 80631
    25 Rocky Mountain Cancer Centers-Greenwood Village Greenwood Village Colorado United States 80111
    26 Rocky Mountain Cancer Centers-Lakewood Lakewood Colorado United States 80228
    27 Saint Anthony Hospital Lakewood Colorado United States 80228
    28 Littleton Adventist Hospital Littleton Colorado United States 80122
    29 Rocky Mountain Cancer Centers-Sky Ridge Lone Tree Colorado United States 80124
    30 Sky Ridge Medical Center Lone Tree Colorado United States 80124
    31 Longmont United Hospital Longmont Colorado United States 80501
    32 Rocky Mountain Cancer Centers-Longmont Longmont Colorado United States 80501
    33 McKee Medical Center Loveland Colorado United States 80539
    34 Parker Adventist Hospital Parker Colorado United States 80138
    35 Rocky Mountain Cancer Centers-Parker Parker Colorado United States 80138
    36 Saint Mary Corwin Medical Center Pueblo Colorado United States 81004
    37 Rocky Mountain Cancer Centers - Pueblo Pueblo Colorado United States 81008
    38 SCL Health Lutheran Medical Center Wheat Ridge Colorado United States 80033
    39 Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut United States 06105
    40 The Hospital of Central Connecticut New Britain Connecticut United States 06050
    41 Beebe Medical Center Lewes Delaware United States 19958
    42 Christiana Gynecologic Oncology LLC Newark Delaware United States 19713
    43 Delaware Clinical and Laboratory Physicians PA Newark Delaware United States 19713
    44 Helen F Graham Cancer Center Newark Delaware United States 19713
    45 Medical Oncology Hematology Consultants PA Newark Delaware United States 19713
    46 Christiana Care Health System-Christiana Hospital Newark Delaware United States 19718
    47 Beebe Health Campus Rehoboth Beach Delaware United States 19971
    48 TidalHealth Nanticoke / Allen Cancer Center Seaford Delaware United States 19973
    49 Christiana Care Health System-Wilmington Hospital Wilmington Delaware United States 19801
    50 University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida United States 33136
    51 Emory University Hospital Midtown Atlanta Georgia United States 30308
    52 Emory University Hospital/Winship Cancer Institute Atlanta Georgia United States 30322
    53 Emory Saint Joseph's Hospital Atlanta Georgia United States 30342
    54 Atlanta VA Medical Center Decatur Georgia United States 30033
    55 Medical Center of Central Georgia Macon Georgia United States 31201
    56 Lewis Cancer and Research Pavilion at Saint Joseph's/Candler Savannah Georgia United States 31405
    57 Saint Alphonsus Cancer Care Center-Boise Boise Idaho United States 83706
    58 Rush - Copley Medical Center Aurora Illinois United States 60504
    59 Saint Joseph Medical Center Bloomington Illinois United States 61701
    60 Illinois CancerCare-Bloomington Bloomington Illinois United States 61704
    61 Illinois CancerCare-Canton Canton Illinois United States 61520
    62 Illinois CancerCare-Carthage Carthage Illinois United States 62321
    63 Centralia Oncology Clinic Centralia Illinois United States 62801
    64 Northwestern University Chicago Illinois United States 60611
    65 Carle on Vermilion Danville Illinois United States 61832
    66 Cancer Care Specialists of Illinois - Decatur Decatur Illinois United States 62526
    67 Decatur Memorial Hospital Decatur Illinois United States 62526
    68 Heartland Cancer Research NCORP Decatur Illinois United States 62526
    69 Carle Physician Group-Effingham Effingham Illinois United States 62401
    70 Crossroads Cancer Center Effingham Illinois United States 62401
    71 Illinois CancerCare-Eureka Eureka Illinois United States 61530
    72 NorthShore University HealthSystem-Evanston Hospital Evanston Illinois United States 60201
    73 Illinois CancerCare-Galesburg Galesburg Illinois United States 61401
    74 NorthShore University HealthSystem-Glenbrook Hospital Glenview Illinois United States 60026
    75 Ingalls Memorial Hospital Harvey Illinois United States 60426
    76 Hematology Oncology Associates of Illinois-Highland Park Highland Park Illinois United States 60035
    77 NorthShore University HealthSystem-Highland Park Hospital Highland Park Illinois United States 60035
    78 Presence Saint Mary's Hospital Kankakee Illinois United States 60901
    79 Illinois CancerCare-Kewanee Clinic Kewanee Illinois United States 61443
    80 AMG Libertyville - Oncology Libertyville Illinois United States 60048
    81 Illinois CancerCare-Macomb Macomb Illinois United States 61455
    82 Carle Physician Group-Mattoon/Charleston Mattoon Illinois United States 61938
    83 Garneau, Stewart C MD (UIA Investigator) Moline Illinois United States 61265
    84 Porubcin, Michael MD (UIA Investigator) Moline Illinois United States 61265
    85 Spector, David MD (UIA Investigator) Moline Illinois United States 61265
    86 Trinity Medical Center Moline Illinois United States 61265
    87 Illinois CancerCare-Monmouth Monmouth Illinois United States 61462
    88 Illinois Cancer Specialists-Niles Niles Illinois United States 60714
    89 Carle Cancer Institute Normal Normal Illinois United States 61761
    90 Illinois CancerCare-Ottawa Clinic Ottawa Illinois United States 61350
    91 Ottawa Regional Hospital and Healthcare Center Ottawa Illinois United States 61350
    92 Illinois CancerCare-Pekin Pekin Illinois United States 61554
    93 OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center Pekin Illinois United States 61554
    94 Proctor Hospital Peoria Illinois United States 61614
    95 Illinois CancerCare-Peoria Peoria Illinois United States 61615
    96 Methodist Medical Center of Illinois Peoria Illinois United States 61636
    97 OSF Saint Francis Medical Center Peoria Illinois United States 61637
    98 Illinois CancerCare-Peru Peru Illinois United States 61354
    99 Illinois Valley Hospital Peru Illinois United States 61354
    100 Illinois CancerCare-Princeton Princeton Illinois United States 61356
    101 Swedish American Hospital Rockford Illinois United States 61104
    102 SwedishAmerican Regional Cancer Center/ACT Rockford Illinois United States 61114
    103 Hematology Oncology Associates of Illinois - Skokie Skokie Illinois United States 60076
    104 Memorial Medical Center Springfield Illinois United States 62781
    105 Carle Cancer Center Urbana Illinois United States 61801
    106 The Carle Foundation Hospital Urbana Illinois United States 61801
    107 Rush-Copley Healthcare Center Yorkville Illinois United States 60560
    108 IU Health Bloomington Bloomington Indiana United States 47403
    109 Elkhart Clinic Elkhart Indiana United States 46514-2098
    110 Michiana Hematology Oncology PC-Elkhart Elkhart Indiana United States 46514
    111 Elkhart General Hospital Elkhart Indiana United States 46515
    112 Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    113 IU Health Central Indiana Cancer Centers-East Indianapolis Indiana United States 46219
    114 Community Howard Regional Health Kokomo Indiana United States 46904
    115 IU Health La Porte Hospital La Porte Indiana United States 46350
    116 Franciscan Saint Anthony Health-Michigan City Michigan City Indiana United States 46360
    117 Woodland Cancer Care Center Michigan City Indiana United States 46360
    118 Michiana Hematology Oncology PC-Mishawaka Mishawaka Indiana United States 46545
    119 Saint Joseph Regional Medical Center-Mishawaka Mishawaka Indiana United States 46545
    120 IU Health Ball Memorial Hospital Muncie Indiana United States 47303
    121 Michiana Hematology Oncology PC-Plymouth Plymouth Indiana United States 46563
    122 Memorial Hospital of South Bend South Bend Indiana United States 46601
    123 Michiana Hematology Oncology PC-South Bend South Bend Indiana United States 46601
    124 South Bend Clinic South Bend Indiana United States 46617
    125 Northern Indiana Cancer Research Consortium South Bend Indiana United States 46628
    126 Michiana Hematology Oncology PC-Westville Westville Indiana United States 46391
    127 Mary Greeley Medical Center Ames Iowa United States 50010
    128 McFarland Clinic PC - Ames Ames Iowa United States 50010
    129 Constantinou, Costas L MD (UIA Investigator) Bettendorf Iowa United States 52722
    130 McFarland Clinic PC-Boone Boone Iowa United States 50036
    131 Mercy Hospital Cedar Rapids Iowa United States 52403
    132 Oncology Associates at Mercy Medical Center Cedar Rapids Iowa United States 52403
    133 Medical Oncology and Hematology Associates-West Des Moines Clive Iowa United States 50325
    134 Mercy Cancer Center-West Lakes Clive Iowa United States 50325
    135 Iowa Methodist Medical Center Des Moines Iowa United States 50309
    136 Iowa-Wide Oncology Research Coalition NCORP Des Moines Iowa United States 50309
    137 Medical Oncology and Hematology Associates-Des Moines Des Moines Iowa United States 50309
    138 Medical Oncology and Hematology Associates-Laurel Des Moines Iowa United States 50314
    139 Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
    140 Iowa Lutheran Hospital Des Moines Iowa United States 50316
    141 McFarland Clinic PC-Jefferson Jefferson Iowa United States 50129
    142 McFarland Clinic PC-Marshalltown Marshalltown Iowa United States 50158
    143 Mercy Medical Center - North Iowa Mason City Iowa United States 50401
    144 Siouxland Regional Cancer Center Sioux City Iowa United States 51101
    145 Mercy Medical Center-Sioux City Sioux City Iowa United States 51102
    146 Saint Luke's Regional Medical Center Sioux City Iowa United States 51104
    147 Mercy Medical Center-West Lakes West Des Moines Iowa United States 50266
    148 Cancer Center of Kansas - Chanute Chanute Kansas United States 66720
    149 Cancer Center of Kansas - Dodge City Dodge City Kansas United States 67801
    150 Cancer Center of Kansas - El Dorado El Dorado Kansas United States 67042
    151 Cancer Center of Kansas - Fort Scott Fort Scott Kansas United States 66701
    152 Cancer Center of Kansas-Independence Independence Kansas United States 67301
    153 Cancer Center of Kansas-Kingman Kingman Kansas United States 67068
    154 Lawrence Memorial Hospital Lawrence Kansas United States 66044
    155 Cancer Center of Kansas-Liberal Liberal Kansas United States 67905
    156 Cancer Center of Kansas-Manhattan Manhattan Kansas United States 66502
    157 Cancer Center of Kansas - McPherson McPherson Kansas United States 67460
    158 Cancer Center of Kansas - Newton Newton Kansas United States 67114
    159 Cancer Center of Kansas - Parsons Parsons Kansas United States 67357
    160 Cancer Center of Kansas - Pratt Pratt Kansas United States 67124
    161 Cancer Center of Kansas - Salina Salina Kansas United States 67401
    162 Cancer Center of Kansas - Wellington Wellington Kansas United States 67152
    163 Associates In Womens Health Wichita Kansas United States 67208
    164 Cancer Center of Kansas-Wichita Medical Arts Tower Wichita Kansas United States 67208
    165 Ascension Via Christi Hospitals Wichita Wichita Kansas United States 67214
    166 Cancer Center of Kansas - Wichita Wichita Kansas United States 67214
    167 Wichita NCI Community Oncology Research Program Wichita Kansas United States 67214
    168 Cancer Center of Kansas - Winfield Winfield Kansas United States 67156
    169 Ochsner Health Center-Summa Baton Rouge Louisiana United States 70809
    170 Ochsner Baptist Medical Center New Orleans Louisiana United States 70115
    171 Ochsner Medical Center Jefferson New Orleans Louisiana United States 70121
    172 York Hospital York Maine United States 03909
    173 Greater Baltimore Medical Center Baltimore Maryland United States 21204
    174 Christiana Care - Union Hospital Elkton Maryland United States 21921
    175 Bixby Medical Center Adrian Michigan United States 49221
    176 Hickman Cancer Center Adrian Michigan United States 49221
    177 Michigan Cancer Research Consortium NCORP Ann Arbor Michigan United States 48106
    178 Saint Joseph Mercy Hospital Ann Arbor Michigan United States 48106
    179 Beaumont Hospital - Dearborn Dearborn Michigan United States 48124
    180 Ascension Saint John Hospital Detroit Michigan United States 48236
    181 Green Bay Oncology - Escanaba Escanaba Michigan United States 49829
    182 Genesys Hurley Cancer Institute Flint Michigan United States 48503
    183 Hurley Medical Center Flint Michigan United States 48503
    184 Green Bay Oncology - Iron Mountain Iron Mountain Michigan United States 49801
    185 Allegiance Health Jackson Michigan United States 49201
    186 Bronson Methodist Hospital Kalamazoo Michigan United States 49007
    187 West Michigan Cancer Center Kalamazoo Michigan United States 49007
    188 Borgess Medical Center Kalamazoo Michigan United States 49048
    189 Sparrow Hospital Lansing Michigan United States 48912
    190 Trinity Health Saint Mary Mercy Livonia Hospital Livonia Michigan United States 48154
    191 Mercy Memorial Hospital Monroe Michigan United States 48162
    192 Toledo Clinic Cancer Centers-Monroe Monroe Michigan United States 48162
    193 Saint Joseph Mercy Oakland Pontiac Michigan United States 48341
    194 Lake Huron Medical Center Port Huron Michigan United States 48060
    195 Ascension Saint Mary's Hospital Saginaw Michigan United States 48601
    196 Lakeland Medical Center Saint Joseph Saint Joseph Michigan United States 49085
    197 Marie Yeager Cancer Center Saint Joseph Michigan United States 49085
    198 Saint John Macomb-Oakland Hospital Warren Michigan United States 48093
    199 Sanford Joe Lueken Cancer Center Bemidji Minnesota United States 56601
    200 Fairview Ridges Hospital Burnsville Minnesota United States 55337
    201 Mercy Hospital Coon Rapids Minnesota United States 55433
    202 Fairview Southdale Hospital Edina Minnesota United States 55435
    203 Unity Hospital Fridley Minnesota United States 55432
    204 Hutchinson Area Health Care Hutchinson Minnesota United States 55350
    205 Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota United States 55109
    206 Saint John's Hospital - Healtheast Maplewood Minnesota United States 55109
    207 Abbott-Northwestern Hospital Minneapolis Minnesota United States 55407
    208 Hennepin County Medical Center Minneapolis Minnesota United States 55415
    209 New Ulm Medical Center New Ulm Minnesota United States 56073
    210 North Memorial Medical Health Center Robbinsdale Minnesota United States 55422
    211 Metro Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota United States 55416
    212 Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota United States 55416
    213 Regions Hospital Saint Paul Minnesota United States 55101
    214 United Hospital Saint Paul Minnesota United States 55102
    215 Saint Francis Regional Medical Center Shakopee Minnesota United States 55379
    216 Lakeview Hospital Stillwater Minnesota United States 55082
    217 Ridgeview Medical Center Waconia Minnesota United States 55387
    218 Rice Memorial Hospital Willmar Minnesota United States 56201
    219 Minnesota Oncology Hematology PA-Woodbury Woodbury Minnesota United States 55125
    220 Saint Francis Medical Center Cape Girardeau Missouri United States 63703
    221 Nebraska Cancer Research Center Lincoln Nebraska United States 68510
    222 Missouri Valley Cancer Consortium Omaha Nebraska United States 68106
    223 Alegent Health Immanuel Medical Center Omaha Nebraska United States 68122
    224 Alegent Health Bergan Mercy Medical Center Omaha Nebraska United States 68124
    225 Alegent Health Lakeside Hospital Omaha Nebraska United States 68130
    226 Creighton University Medical Center Omaha Nebraska United States 68131
    227 Cancer and Blood Specialists-Henderson Henderson Nevada United States 89052
    228 Comprehensive Cancer Centers of Nevada - Henderson Henderson Nevada United States 89052
    229 Las Vegas Cancer Center-Henderson Henderson Nevada United States 89052
    230 Comprehensive Cancer Centers of Nevada-Southeast Henderson Henderson Nevada United States 89074
    231 GenesisCare USA - Henderson Henderson Nevada United States 89074
    232 University Medical Center of Southern Nevada Las Vegas Nevada United States 89102
    233 Cancer and Blood Specialists-Shadow Las Vegas Nevada United States 89106
    234 Radiation Oncology Centers of Nevada Central Las Vegas Nevada United States 89106
    235 GenesisCare USA - Las Vegas Las Vegas Nevada United States 89109
    236 HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway Las Vegas Nevada United States 89109
    237 HealthCare Partners Medical Group Oncology/Hematology-San Martin Las Vegas Nevada United States 89113
    238 Radiation Oncology Centers of Nevada Southeast Las Vegas Nevada United States 89119
    239 Cancer Therapy and Integrative Medicine Las Vegas Nevada United States 89121
    240 Cancer and Blood Specialists-Tenaya Las Vegas Nevada United States 89128
    241 Comprehensive Cancer Centers of Nevada - Northwest Las Vegas Nevada United States 89128
    242 GenesisCare USA - Vegas Tenaya Las Vegas Nevada United States 89128
    243 HealthCare Partners Medical Group Oncology/Hematology-Tenaya Las Vegas Nevada United States 89128
    244 Comprehensive Cancer Centers of Nevada-Summerlin Las Vegas Nevada United States 89144
    245 Las Vegas Cancer Center-Medical Center Las Vegas Nevada United States 89148-2405
    246 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89148
    247 GenesisCare USA - Fort Apache Las Vegas Nevada United States 89148
    248 OptumCare Cancer Care at Fort Apache Las Vegas Nevada United States 89148
    249 HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills Las Vegas Nevada United States 89149
    250 Comprehensive Cancer Centers of Nevada - Central Valley Las Vegas Nevada United States 89169
    251 Nevada Cancer Research Foundation NCORP Las Vegas Nevada United States 89169
    252 Cooper Hospital University Medical Center Camden New Jersey United States 08103
    253 Veterans Adminstration New Jersey Health Care System East Orange New Jersey United States 07018-1095
    254 Hackensack University Medical Center Hackensack New Jersey United States 07601
    255 Monmouth Medical Center Long Branch New Jersey United States 07740
    256 Morristown Medical Center Morristown New Jersey United States 07960
    257 Virtua Memorial Mount Holly New Jersey United States 08060
    258 Rutgers New Jersey Medical School Newark New Jersey United States 07101
    259 Overlook Hospital Summit New Jersey United States 07902
    260 Inspira Medical Center Vineland Vineland New Jersey United States 08360
    261 University of New Mexico Cancer Center Albuquerque New Mexico United States 87102
    262 Memorial Medical Center - Las Cruces Las Cruces New Mexico United States 88011
    263 Montefiore Medical Center-Weiler Hospital Bronx New York United States 10461
    264 Montefiore Medical Center - Moses Campus Bronx New York United States 10467
    265 Stony Brook University Medical Center Stony Brook New York United States 11794
    266 Dickstein Cancer Treatment Center White Plains New York United States 10601
    267 Sanford Broadway Medical Center Fargo North Dakota United States 58122
    268 Sanford Clinic North-Fargo Fargo North Dakota United States 58122
    269 Sanford Roger Maris Cancer Center Fargo North Dakota United States 58122
    270 Summa Health System - Akron Campus Akron Ohio United States 44304
    271 Strecker Cancer Center-Belpre Belpre Ohio United States 45714
    272 Toledo Clinic Cancer Centers-Bowling Green Bowling Green Ohio United States 43402
    273 Cleveland Clinic Mercy Hospital Canton Ohio United States 44708
    274 Adena Regional Medical Center Chillicothe Ohio United States 45601
    275 Case Western Reserve University Cleveland Ohio United States 44106
    276 MetroHealth Medical Center Cleveland Ohio United States 44109
    277 Columbus Oncology and Hematology Associates Inc Columbus Ohio United States 43214
    278 Riverside Methodist Hospital Columbus Ohio United States 43214
    279 Columbus NCI Community Oncology Research Program Columbus Ohio United States 43215
    280 Grant Medical Center Columbus Ohio United States 43215
    281 The Mark H Zangmeister Center Columbus Ohio United States 43219
    282 Mount Carmel Health Center West Columbus Ohio United States 43222
    283 Doctors Hospital Columbus Ohio United States 43228
    284 Delaware Health Center-Grady Cancer Center Delaware Ohio United States 43015
    285 Delaware Radiation Oncology Delaware Ohio United States 43015
    286 Grady Memorial Hospital Delaware Ohio United States 43015
    287 Fairfield Medical Center Lancaster Ohio United States 43130
    288 Saint Rita's Medical Center Lima Ohio United States 45801
    289 Lima Memorial Hospital Lima Ohio United States 45804
    290 Marietta Memorial Hospital Marietta Ohio United States 45750
    291 Toledo Clinic Cancer Centers-Maumee Maumee Ohio United States 43537
    292 Knox Community Hospital Mount Vernon Ohio United States 43050
    293 Licking Memorial Hospital Newark Ohio United States 43055
    294 Newark Radiation Oncology Newark Ohio United States 43055
    295 Saint Charles Hospital Oregon Ohio United States 43616
    296 Toledo Clinic Cancer Centers-Oregon Oregon Ohio United States 43616
    297 Southern Ohio Medical Center Portsmouth Ohio United States 45662
    298 Springfield Regional Medical Center Springfield Ohio United States 45505
    299 ProMedica Flower Hospital Sylvania Ohio United States 43560
    300 Mercy Hospital of Tiffin Tiffin Ohio United States 44883
    301 ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital Toledo Ohio United States 43606
    302 Saint Vincent Mercy Medical Center Toledo Ohio United States 43608
    303 University of Toledo Toledo Ohio United States 43614
    304 Toledo Community Hospital Oncology Program CCOP Toledo Ohio United States 43617
    305 Mercy Health - Saint Anne Hospital Toledo Ohio United States 43623
    306 Toledo Clinic Cancer Centers-Toledo Toledo Ohio United States 43623
    307 Fulton County Health Center Wauseon Ohio United States 43567
    308 Saint Ann's Hospital Westerville Ohio United States 43081
    309 Genesis Healthcare System Cancer Care Center Zanesville Ohio United States 43701
    310 Bryn Mawr Hospital Bryn Mawr Pennsylvania United States 19010
    311 Geisinger Medical Center Danville Pennsylvania United States 17822
    312 Doylestown Hospital Doylestown Pennsylvania United States 18901
    313 UPMC Hillman Cancer Center Erie Erie Pennsylvania United States 16505
    314 Geisinger Medical Center-Cancer Center Hazleton Hazleton Pennsylvania United States 18201
    315 Penn State Milton S Hershey Medical Center Hershey Pennsylvania United States 17033-0850
    316 Lancaster General Hospital Lancaster Pennsylvania United States 17602
    317 Geisinger Medical Oncology-Lewisburg Lewisburg Pennsylvania United States 17837
    318 Paoli Memorial Hospital Paoli Pennsylvania United States 19301
    319 Thomas Jefferson University Hospital Philadelphia Pennsylvania United States 19107
    320 Einstein Medical Center Philadelphia Philadelphia Pennsylvania United States 19141
    321 Geisinger Cancer Services-Pottsville Pottsville Pennsylvania United States 17901
    322 Guthrie Medical Group PC-Robert Packer Hospital Sayre Pennsylvania United States 18840
    323 Geisinger Medical Group State College Pennsylvania United States 16801
    324 Geisinger Wyoming Valley/Henry Cancer Center Wilkes-Barre Pennsylvania United States 18711
    325 Lankenau Medical Center Wynnewood Pennsylvania United States 19096
    326 Main Line Health NCORP Wynnewood Pennsylvania United States 19096
    327 WellSpan Health-York Hospital York Pennsylvania United States 17403
    328 Sanford Cancer Center Oncology Clinic Sioux Falls South Dakota United States 57104
    329 Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota United States 57117-5134
    330 Dell Seton Medical Center at The University of Texas Austin Texas United States 78701
    331 Cancer Therapy and Research Center at The UT Health Science Center at San Antonio San Antonio Texas United States 78229
    332 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229
    333 University of Texas Health Science Center at Tyler Tyler Texas United States 75708
    334 Fredericksburg Oncology Inc Fredericksburg Virginia United States 22401
    335 West Virginia University Charleston Division Charleston West Virginia United States 25304
    336 West Virginia University Healthcare Morgantown West Virginia United States 26506
    337 Wheeling Hospital/Schiffler Cancer Center Wheeling West Virginia United States 26003
    338 Marshfield Clinic-Chippewa Center Chippewa Falls Wisconsin United States 54729
    339 HSHS Sacred Heart Hospital Eau Claire Wisconsin United States 54701
    340 Marshfield Clinic Cancer Center at Sacred Heart Eau Claire Wisconsin United States 54701
    341 Green Bay Oncology at Saint Vincent Hospital Green Bay Wisconsin United States 54301-3526
    342 Saint Vincent Hospital Cancer Center Green Bay Green Bay Wisconsin United States 54301
    343 Green Bay Oncology Limited at Saint Mary's Hospital Green Bay Wisconsin United States 54303
    344 Saint Vincent Hospital Cancer Center at Saint Mary's Green Bay Wisconsin United States 54303
    345 UW Cancer Center Johnson Creek Johnson Creek Wisconsin United States 53038
    346 Dean Hematology and Oncology Clinic Madison Wisconsin United States 53717
    347 University of Wisconsin Carbone Cancer Center Madison Wisconsin United States 53792
    348 Holy Family Memorial Hospital Manitowoc Wisconsin United States 54221
    349 Bay Area Medical Center Marinette Wisconsin United States 54143
    350 Marshfield Medical Center-Marshfield Marshfield Wisconsin United States 54449
    351 Marshfield Medical Center Marshfield Wisconsin United States 54449
    352 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    353 Marshfield Clinic-Minocqua Center Minocqua Wisconsin United States 54548
    354 Cancer Center of Western Wisconsin New Richmond Wisconsin United States 54017
    355 ProHealth Oconomowoc Memorial Hospital Oconomowoc Wisconsin United States 53066
    356 Saint Vincent Hospital Cancer Center at Oconto Falls Oconto Falls Wisconsin United States 54154
    357 Ascension Saint Mary's Hospital Rhinelander Wisconsin United States 54501
    358 Saint Mary's Hospital Rhinelander Wisconsin United States 54501
    359 Marshfield Medical Center-Rice Lake Rice Lake Wisconsin United States 54868
    360 HSHS Saint Nicholas Hospital Sheboygan Wisconsin United States 53081
    361 Ascension Saint Michael's Hospital Stevens Point Wisconsin United States 54481
    362 Green Bay Oncology - Sturgeon Bay Sturgeon Bay Wisconsin United States 54235
    363 ProHealth Waukesha Memorial Hospital Waukesha Wisconsin United States 53188
    364 Marshfield Clinic-Wausau Center Wausau Wisconsin United States 54401
    365 Ascension Saint Clare's Hospital Weston Wisconsin United States 54476
    366 Diagnostic and Treatment Center Weston Wisconsin United States 54476
    367 Marshfield Medical Center - Weston Weston Wisconsin United States 54476
    368 Aspirus Cancer Care - Wisconsin Rapids Wisconsin Rapids Wisconsin United States 54494
    369 Marshfield Clinic - Wisconsin Rapids Center Wisconsin Rapids Wisconsin United States 54494

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Joel W Neal, ECOG-ACRIN Cancer Research Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01708954
    Other Study ID Numbers:
    • NCI-2012-01938
    • NCI-2012-01938
    • ECOG-E1512
    • CDR0000741879
    • E1512
    • E1512
    • U10CA180820
    • U10CA021115
    First Posted:
    Oct 17, 2012
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    Apr 1, 2022

    Study Results

    Participant Flow

    Recruitment Details This study was activated on February 7, 2013 and closed to accrual on July 1, 2014 with final accrual of 125 patients. Among these, a total of 20 patients registered to Step 2.
    Pre-assignment Detail
    Arm/Group Title Arm A (Erlotinib) Arm B (Cabozantinib) Arm C (Erlotinib+Cabozantinib)
    Arm/Group Description Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Period Title: Step 1
    STARTED 42 40 43
    Started Protocol Therapy 40 40 39
    Eligible and Treated 38 38 35
    Patients With MET Status Data Available 30 32 24
    COMPLETED 0 0 0
    NOT COMPLETED 42 40 43
    Period Title: Step 1
    STARTED 13 7 0
    COMPLETED 0 0 0
    NOT COMPLETED 13 7 0

    Baseline Characteristics

    Arm/Group Title Arm A (Erlotinib) Arm B (Cabozantinib) Arm C (Erlotinib+Cabozantinib) Total
    Arm/Group Description Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Total of all reporting groups
    Overall Participants 38 38 35 111
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    68
    65
    63
    66
    Sex: Female, Male (Count of Participants)
    Female
    20
    52.6%
    24
    63.2%
    17
    48.6%
    61
    55%
    Male
    18
    47.4%
    14
    36.8%
    18
    51.4%
    50
    45%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival (PFS)
    Description PFS is defined as the time from randomization to documented disease progression or death from any cause, whichever occurred first. Patients who had not experienced an event of interest by the time of analysis were censored at the date of last disease assessment.
    Time Frame Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Eligible and treated patients
    Arm/Group Title Arm A (Erlotinib) Arm B (Cabozantinib) Arm C (Erlotinib+Cabozantinib)
    Arm/Group Description Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 38 38 35
    Median (95% Confidence Interval) [months]
    1.8
    4.3
    4.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Erlotinib), Arm C (Erlotinib+Cabozantinib)
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.37
    Confidence Interval (2-Sided) 80%
    0.25 to 0.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio of Arm C/Arm A
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A (Erlotinib), Arm B (Cabozantinib)
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.39
    Confidence Interval (2-Sided) 80%
    0.27 to 0.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio of Arm B/Arm A
    2. Secondary Outcome
    Title Overall Survival (OS)
    Description OS is defined as the time from randomization to death from any cause or date of last known alive.
    Time Frame Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Eligible and treated patients
    Arm/Group Title Arm A (Erlotinib) Arm B (Cabozantinib) Arm C (Erlotinib+Cabozantinib)
    Arm/Group Description Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 38 38 35
    Median (95% Confidence Interval) [months]
    5.1
    9.2
    13.3
    3. Secondary Outcome
    Title Proportion of Patients With Objective Response
    Description Objective response is defined as complete response (CR) or partial response (PR) evaluated using RECIST v 1.1. CR is defined as disappearance of all lesions and any pathological lymph nodes must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions and persistence of one or more non-target lesion(s).
    Time Frame Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Eligible and treated patients
    Arm/Group Title Arm A (Erlotinib) Arm B (Cabozantinib) Arm C (Erlotinib+Cabozantinib)
    Arm/Group Description Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 38 38 35
    Number (95% Confidence Interval) [proportion of participants]
    0.03
    0.1%
    0.11
    0.3%
    0.03
    0.1%
    4. Secondary Outcome
    Title Proportion of Patients With MET Positivity
    Description Submission of archival tissue for central MET IHC testing was required for this study, and total MET IHC testing was conducted at the Brigham and Women's Hospital using the c-Met clone CVD13 (arabbit polyclonal). Membranous and cytoplasmic staining were individually scored, and positivity was declared if MET was expressed in either the membrane or cytoplasm.
    Time Frame Assessed at baseline

    Outcome Measure Data

    Analysis Population Description
    Eligible and treated patients who had sufficient samples for MET expression analysis.
    Arm/Group Title Arm A (Erlotinib) Arm B (Cabozantinib) Arm C (Erlotinib+Cabozantinib)
    Arm/Group Description Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 30 32 24
    Number (95% Confidence Interval) [proportion of participants]
    0.80
    2.1%
    0.81
    2.1%
    0.96
    2.7%
    5. Secondary Outcome
    Title Proportion of Patients With Worst Grade Toxicities of Grade 3 or Higher
    Description
    Time Frame Assessed every 4 weeks while on treatment and for 30 days after the end of treatment

    Outcome Measure Data

    Analysis Population Description
    All patients who received protocol therapy
    Arm/Group Title Arm A (Erlotinib) Arm B (Cabozantinib) Arm C (Erlotinib+Cabozantinib)
    Arm/Group Description Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants 40 40 39
    Number (90% Confidence Interval) [Proportion of participants]
    0.325
    0.9%
    0.70
    1.8%
    0.718
    2.1%

    Adverse Events

    Time Frame Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
    Adverse Event Reporting Description
    Arm/Group Title Arm A (Erlotinib) Arm B (Cabozantinib) Arm C (Erlotinib+Cabozantinib) Arm Z (Erlotinib+Cabozantinib; Step 2)
    Arm/Group Description Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression in Arm A or Arm B may receive erlotinib 150mg and cabozantinib 40mg as patients in Arm C. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    All Cause Mortality
    Arm A (Erlotinib) Arm B (Cabozantinib) Arm C (Erlotinib+Cabozantinib) Arm Z (Erlotinib+Cabozantinib; Step 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Arm A (Erlotinib) Arm B (Cabozantinib) Arm C (Erlotinib+Cabozantinib) Arm Z (Erlotinib+Cabozantinib; Step 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 13/40 (32.5%) 28/40 (70%) 28/39 (71.8%) 12/20 (60%)
    Blood and lymphatic system disorders
    Anemia 1/40 (2.5%) 1/40 (2.5%) 1/39 (2.6%) 0/20 (0%)
    Cardiac disorders
    Atrial fibrillation 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Myocardial infarction 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Sinus tachycardia 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Diarrhea 3/40 (7.5%) 3/40 (7.5%) 11/39 (28.2%) 8/20 (40%)
    Ileus 0/40 (0%) 0/40 (0%) 0/39 (0%) 1/20 (5%)
    Mucositis oral 0/40 (0%) 4/40 (10%) 1/39 (2.6%) 0/20 (0%)
    Nausea 1/40 (2.5%) 2/40 (5%) 1/39 (2.6%) 1/20 (5%)
    Pancreatitis 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Vomiting 1/40 (2.5%) 1/40 (2.5%) 1/39 (2.6%) 1/20 (5%)
    Gastrointestinal disorders - Other, specify 0/40 (0%) 0/40 (0%) 0/39 (0%) 1/20 (5%)
    General disorders
    Fatigue 5/40 (12.5%) 6/40 (15%) 6/39 (15.4%) 1/20 (5%)
    Hepatobiliary disorders
    Portal vein thrombosis 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Infections and infestations
    Lung infection 0/40 (0%) 2/40 (5%) 0/39 (0%) 0/20 (0%)
    Skin infection 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Urinary tract infection 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Injury, poisoning and procedural complications
    Fall 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Investigations
    Aspartate aminotransferase increased 0/40 (0%) 0/40 (0%) 0/39 (0%) 1/20 (5%)
    Blood bilirubin increased 1/40 (2.5%) 0/40 (0%) 1/39 (2.6%) 0/20 (0%)
    Lipase increased 1/40 (2.5%) 2/40 (5%) 0/39 (0%) 0/20 (0%)
    Lymphocyte count decreased 0/40 (0%) 1/40 (2.5%) 1/39 (2.6%) 0/20 (0%)
    Neutrophil count decreased 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Platelet count decreased 0/40 (0%) 0/40 (0%) 1/39 (2.6%) 0/20 (0%)
    Weight loss 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Metabolism and nutrition disorders
    Anorexia 2/40 (5%) 1/40 (2.5%) 3/39 (7.7%) 1/20 (5%)
    Dehydration 1/40 (2.5%) 0/40 (0%) 1/39 (2.6%) 3/20 (15%)
    Hypocalcemia 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Hypokalemia 1/40 (2.5%) 0/40 (0%) 0/39 (0%) 1/20 (5%)
    Hypomagnesemia 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Hyponatremia 0/40 (0%) 1/40 (2.5%) 3/39 (7.7%) 1/20 (5%)
    Musculoskeletal and connective tissue disorders
    Bone pain 0/40 (0%) 0/40 (0%) 1/39 (2.6%) 0/20 (0%)
    Generalized muscle weakness 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Muscle weakness lower limb 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Nervous system disorders
    Cognitive disturbance 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Dysphasia 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Intracranial hemorrhage 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Peripheral sensory neuropathy 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Syncope 0/40 (0%) 0/40 (0%) 3/39 (7.7%) 0/20 (0%)
    Psychiatric disorders
    Confusion 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Insomnia 1/40 (2.5%) 0/40 (0%) 0/39 (0%) 0/20 (0%)
    Renal and urinary disorders
    Proteinuria 0/40 (0%) 2/40 (5%) 0/39 (0%) 0/20 (0%)
    Reproductive system and breast disorders
    Vaginal fistula 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 0/40 (0%) 2/40 (5%) 1/39 (2.6%) 0/20 (0%)
    Pneumonitis 0/40 (0%) 0/40 (0%) 1/39 (2.6%) 0/20 (0%)
    Respiratory failure 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Skin and subcutaneous tissue disorders
    Palmar-plantar erythrodysesthesia syndrome 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Rash acneiform 1/40 (2.5%) 1/40 (2.5%) 2/39 (5.1%) 0/20 (0%)
    Rash maculo-papular 0/40 (0%) 0/40 (0%) 1/39 (2.6%) 0/20 (0%)
    Skin and subcutaneous tissue disorders - Other, specify 0/40 (0%) 0/40 (0%) 1/39 (2.6%) 0/20 (0%)
    Vascular disorders
    Hypertension 0/40 (0%) 10/40 (25%) 1/39 (2.6%) 0/20 (0%)
    Hypotension 0/40 (0%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)
    Thromboembolic event 0/40 (0%) 3/40 (7.5%) 2/39 (5.1%) 2/20 (10%)
    Other (Not Including Serious) Adverse Events
    Arm A (Erlotinib) Arm B (Cabozantinib) Arm C (Erlotinib+Cabozantinib) Arm Z (Erlotinib+Cabozantinib; Step 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 35/40 (87.5%) 40/40 (100%) 38/39 (97.4%) 19/20 (95%)
    Blood and lymphatic system disorders
    Anemia 6/40 (15%) 12/40 (30%) 13/39 (33.3%) 1/20 (5%)
    Cardiac disorders
    Atrial fibrillation 0/40 (0%) 2/40 (5%) 0/39 (0%) 0/20 (0%)
    Sinus tachycardia 0/40 (0%) 0/40 (0%) 0/39 (0%) 1/20 (5%)
    Endocrine disorders
    Hyperthyroidism 0/40 (0%) 5/40 (12.5%) 1/39 (2.6%) 0/20 (0%)
    Hypothyroidism 0/40 (0%) 10/40 (25%) 2/39 (5.1%) 1/20 (5%)
    Endocrine disorders - Other, specify 0/40 (0%) 1/40 (2.5%) 2/39 (5.1%) 0/20 (0%)
    Eye disorders
    Conjunctivitis 3/40 (7.5%) 0/40 (0%) 0/39 (0%) 1/20 (5%)
    Dry eye 2/40 (5%) 2/40 (5%) 2/39 (5.1%) 0/20 (0%)
    Watering eyes 1/40 (2.5%) 1/40 (2.5%) 2/39 (5.1%) 0/20 (0%)
    Gastrointestinal disorders
    Abdominal pain 4/40 (10%) 4/40 (10%) 4/39 (10.3%) 3/20 (15%)
    Bloating 0/40 (0%) 2/40 (5%) 0/39 (0%) 0/20 (0%)
    Constipation 1/40 (2.5%) 6/40 (15%) 4/39 (10.3%) 0/20 (0%)
    Diarrhea 24/40 (60%) 23/40 (57.5%) 31/39 (79.5%) 15/20 (75%)
    Dry mouth 3/40 (7.5%) 3/40 (7.5%) 6/39 (15.4%) 2/20 (10%)
    Dyspepsia 2/40 (5%) 4/40 (10%) 5/39 (12.8%) 0/20 (0%)
    Dysphagia 3/40 (7.5%) 2/40 (5%) 0/39 (0%) 0/20 (0%)
    Flatulence 0/40 (0%) 3/40 (7.5%) 1/39 (2.6%) 0/20 (0%)
    Gastroesophageal reflux disease 0/40 (0%) 2/40 (5%) 0/39 (0%) 0/20 (0%)
    Mucositis oral 2/40 (5%) 17/40 (42.5%) 9/39 (23.1%) 1/20 (5%)
    Nausea 8/40 (20%) 19/40 (47.5%) 17/39 (43.6%) 4/20 (20%)
    Oral pain 0/40 (0%) 2/40 (5%) 4/39 (10.3%) 1/20 (5%)
    Proctitis 0/40 (0%) 0/40 (0%) 0/39 (0%) 1/20 (5%)
    Rectal hemorrhage 0/40 (0%) 1/40 (2.5%) 2/39 (5.1%) 0/20 (0%)
    Vomiting 4/40 (10%) 5/40 (12.5%) 11/39 (28.2%) 1/20 (5%)
    Gastrointestinal disorders - Other, specify 0/40 (0%) 2/40 (5%) 0/39 (0%) 1/20 (5%)
    General disorders
    Chills 1/40 (2.5%) 2/40 (5%) 0/39 (0%) 1/20 (5%)
    Edema limbs 0/40 (0%) 4/40 (10%) 1/39 (2.6%) 0/20 (0%)
    Fatigue 20/40 (50%) 27/40 (67.5%) 32/39 (82.1%) 13/20 (65%)
    Fever 0/40 (0%) 2/40 (5%) 0/39 (0%) 1/20 (5%)
    Pain 0/40 (0%) 2/40 (5%) 0/39 (0%) 0/20 (0%)
    Infections and infestations
    Paronychia 0/40 (0%) 0/40 (0%) 2/39 (5.1%) 0/20 (0%)
    Skin infection 1/40 (2.5%) 2/40 (5%) 0/39 (0%) 1/20 (5%)
    Upper respiratory infection 0/40 (0%) 0/40 (0%) 0/39 (0%) 1/20 (5%)
    Investigations
    Alanine aminotransferase increased 4/40 (10%) 21/40 (52.5%) 13/39 (33.3%) 4/20 (20%)
    Alkaline phosphatase increased 2/40 (5%) 8/40 (20%) 3/39 (7.7%) 2/20 (10%)
    Aspartate aminotransferase increased 8/40 (20%) 26/40 (65%) 17/39 (43.6%) 10/20 (50%)
    Blood bilirubin increased 5/40 (12.5%) 5/40 (12.5%) 4/39 (10.3%) 2/20 (10%)
    Creatinine increased 1/40 (2.5%) 5/40 (12.5%) 3/39 (7.7%) 1/20 (5%)
    Lipase increased 2/40 (5%) 1/40 (2.5%) 3/39 (7.7%) 2/20 (10%)
    Lymphocyte count decreased 1/40 (2.5%) 5/40 (12.5%) 5/39 (12.8%) 2/20 (10%)
    Neutrophil count decreased 0/40 (0%) 2/40 (5%) 2/39 (5.1%) 0/20 (0%)
    Platelet count decreased 1/40 (2.5%) 14/40 (35%) 8/39 (20.5%) 2/20 (10%)
    Weight loss 6/40 (15%) 13/40 (32.5%) 13/39 (33.3%) 5/20 (25%)
    White blood cell decreased 1/40 (2.5%) 9/40 (22.5%) 5/39 (12.8%) 0/20 (0%)
    Metabolism and nutrition disorders
    Anorexia 11/40 (27.5%) 16/40 (40%) 19/39 (48.7%) 7/20 (35%)
    Dehydration 2/40 (5%) 2/40 (5%) 5/39 (12.8%) 0/20 (0%)
    Hypercalcemia 2/40 (5%) 0/40 (0%) 1/39 (2.6%) 0/20 (0%)
    Hyperglycemia 1/40 (2.5%) 3/40 (7.5%) 2/39 (5.1%) 0/20 (0%)
    Hyperkalemia 0/40 (0%) 2/40 (5%) 0/39 (0%) 0/20 (0%)
    Hypoalbuminemia 2/40 (5%) 9/40 (22.5%) 4/39 (10.3%) 3/20 (15%)
    Hypocalcemia 1/40 (2.5%) 4/40 (10%) 7/39 (17.9%) 0/20 (0%)
    Hypokalemia 4/40 (10%) 4/40 (10%) 7/39 (17.9%) 2/20 (10%)
    Hypomagnesemia 6/40 (15%) 13/40 (32.5%) 13/39 (33.3%) 2/20 (10%)
    Hyponatremia 3/40 (7.5%) 3/40 (7.5%) 3/39 (7.7%) 1/20 (5%)
    Musculoskeletal and connective tissue disorders
    Generalized muscle weakness 0/40 (0%) 2/40 (5%) 4/39 (10.3%) 1/20 (5%)
    Myalgia 2/40 (5%) 1/40 (2.5%) 1/39 (2.6%) 0/20 (0%)
    Nervous system disorders
    Dizziness 1/40 (2.5%) 3/40 (7.5%) 5/39 (12.8%) 0/20 (0%)
    Dysgeusia 6/40 (15%) 12/40 (30%) 11/39 (28.2%) 6/20 (30%)
    Headache 1/40 (2.5%) 2/40 (5%) 1/39 (2.6%) 0/20 (0%)
    Lethargy 0/40 (0%) 2/40 (5%) 0/39 (0%) 0/20 (0%)
    Peripheral sensory neuropathy 0/40 (0%) 5/40 (12.5%) 1/39 (2.6%) 0/20 (0%)
    Psychiatric disorders
    Anxiety 0/40 (0%) 0/40 (0%) 2/39 (5.1%) 0/20 (0%)
    Renal and urinary disorders
    Chronic kidney disease 0/40 (0%) 2/40 (5%) 1/39 (2.6%) 0/20 (0%)
    Hematuria 0/40 (0%) 2/40 (5%) 0/39 (0%) 1/20 (5%)
    Proteinuria 1/40 (2.5%) 13/40 (32.5%) 18/39 (46.2%) 0/20 (0%)
    Renal and urinary disorders - Other, specify 0/40 (0%) 0/40 (0%) 0/39 (0%) 1/20 (5%)
    Respiratory, thoracic and mediastinal disorders
    Cough 2/40 (5%) 2/40 (5%) 3/39 (7.7%) 1/20 (5%)
    Dyspnea 1/40 (2.5%) 3/40 (7.5%) 6/39 (15.4%) 2/20 (10%)
    Epistaxis 1/40 (2.5%) 2/40 (5%) 1/39 (2.6%) 1/20 (5%)
    Hoarseness 0/40 (0%) 2/40 (5%) 2/39 (5.1%) 0/20 (0%)
    Pneumonitis 0/40 (0%) 0/40 (0%) 0/39 (0%) 1/20 (5%)
    Sore throat 1/40 (2.5%) 3/40 (7.5%) 0/39 (0%) 0/20 (0%)
    Voice alteration 1/40 (2.5%) 3/40 (7.5%) 3/39 (7.7%) 0/20 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/40 (2.5%) 2/40 (5%) 2/39 (5.1%) 1/20 (5%)
    Dry skin 9/40 (22.5%) 9/40 (22.5%) 10/39 (25.6%) 3/20 (15%)
    Nail loss 0/40 (0%) 0/40 (0%) 0/39 (0%) 1/20 (5%)
    Palmar-plantar erythrodysesthesia syndrome 3/40 (7.5%) 6/40 (15%) 6/39 (15.4%) 2/20 (10%)
    Pruritus 5/40 (12.5%) 2/40 (5%) 7/39 (17.9%) 1/20 (5%)
    Rash acneiform 23/40 (57.5%) 6/40 (15%) 25/39 (64.1%) 9/20 (45%)
    Rash maculo-papular 3/40 (7.5%) 4/40 (10%) 6/39 (15.4%) 3/20 (15%)
    Skin hypopigmentation 0/40 (0%) 2/40 (5%) 0/39 (0%) 0/20 (0%)
    Skin and subcutaneous tissue disorders - Other, specify 0/40 (0%) 4/40 (10%) 3/39 (7.7%) 0/20 (0%)
    Vascular disorders
    Hypertension 4/40 (10%) 10/40 (25%) 17/39 (43.6%) 4/20 (20%)
    Thromboembolic event 2/40 (5%) 1/40 (2.5%) 0/39 (0%) 0/20 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Study Statistician
    Organization ECOG-ACRIN Statistical Office
    Phone 617-632-3012
    Email
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01708954
    Other Study ID Numbers:
    • NCI-2012-01938
    • NCI-2012-01938
    • ECOG-E1512
    • CDR0000741879
    • E1512
    • E1512
    • U10CA180820
    • U10CA021115
    First Posted:
    Oct 17, 2012
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    Apr 1, 2022