S0727 Gemcitabine Hydrochloride and Erlotinib Hydrochloride With or Without Monoclonal Antibody Therapy in Treating Patients With Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00617708
Collaborator
(none)
134
146
2
71.9
0.9
0

Study Details

Study Description

Brief Summary

This randomized phase I/II trial is studying the side effects and best dose of monoclonal antibody therapy when given together with gemcitabine hydrochloride and erlotinib hydrochloride and to see how well they work compared with giving gemcitabine hydrochloride and erlotinib hydrochloride alone as first-line therapy in treating patients with metastatic pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving erlotinib hydrochloride and gemcitabine hydrochloride together with monoclonal antibody therapy may kill more tumor cells.

Condition or Disease Intervention/Treatment Phase
  • Biological: cixutumumab
  • Drug: erlotinib hydrochloride
  • Drug: gemcitabine hydrochloride
Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To assess the appropriate dose of IMC-A12 (cixutumumab) to use in combination with gemcitabine (gemcitabine hydrochloride) and erlotinib (erlotinib hydrochloride). (Phase I)
  2. To assess progression-free survival in patients with metastatic pancreatic cancer treated with IMC-A12 plus gemcitabine and erlotinib compared to those treated with gemcitabine plus erlotinib alone. (Phase II) III. To assess overall survival in each of the two treatment arms in this group of patients. (Phase II) IV. To assess the total response probability (confirmed and unconfirmed, complete and partial responses) in each of the two treatment arms in the subset of this group of patients with measurable disease. (Phase II) V. To assess the qualitative and quantitative toxicities in each of the two treatment arms in this group of patients. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of cixutumumab followed by a randomized, phase II study.

Patients are initially enrolled into the phase I portion of the study to determine the recommended phase II dose (RPTD) of cixutumumab. Once the RPTD is determined, patients are enrolled into the phase II portion of the study.

PHASE I (LIMITED INSTITUTIONS): Patients receive erlotinib hydrochloride orally (PO) once daily on days 1-28, gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II (ALL SWOG MEMBERS): Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive erlotinib hydrochloride, gemcitabine hydrochloride, and cixutumumab at the RPTD as in phase I.

ARM II: Patients receive erlotinib hydrochloride and gemcitabine hydrochloride as in arm I.

In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Previously collected tumor tissue is obtained for gene expression analyses by RT-PCR, RNA isolation, and cDNA synthesis. Blood samples are collected periodically for correlative studies. Samples are assessed for the potential relationship between gene expression levels, germline polymorphisms, Ras and P13K mutations and progression-free survival and overall survival.

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

Study Design

Study Type:
Interventional
Actual Enrollment :
134 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I and Randomized Phase II Trial of Gemcitabine + Erlotinib (NSC-718781) + IMC-A12 (NSC-742460) vs. Gemcitabine + Erlotinib as First-Line Treatment in Patients With Metastatic Pancreatic Cancer
Study Start Date :
Mar 1, 2008
Actual Primary Completion Date :
Sep 1, 2012
Actual Study Completion Date :
Feb 25, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I (erlotinib, gemcitabine, cixutumumab)

Patients receive erlotinib hydrochloride PO once daily on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: cixutumumab
Given IV
Other Names:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
  • Drug: erlotinib hydrochloride
    Given PO
    Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
  • Drug: gemcitabine hydrochloride
    Given IV
    Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
  • Active Comparator: Arm II (erlotinib, gemcitabine)

    Patients receive erlotinib hydrochloride and gemcitabine hydrochloride as in arm I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: erlotinib hydrochloride
    Given PO
    Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
  • Drug: gemcitabine hydrochloride
    Given IV
    Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose Determination [28 days]

      Maximum dose of IMC-A12 (in combination with erlotinib and gemcitabine) at which 3/10 or fewer patients have dose-limiting toxicities (DLT). Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0). DLT apply only during cycle 1 and should be drug-related (possible, probable, or definite).

    2. Progression-Free Survival [Up to 3 years]

      From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.

    Secondary Outcome Measures

    1. Overall Survival [Up to 3 years]

      From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

    2. Response [Up to 3 years]

      Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

    3. Toxicity [Up to 3 years]

      Number of patients with Grade 3 through 5 adverse events that are related to study drug. Only adverse events that are possibly, probably or definitely related to study drug are reported.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically or cytologically confirmed pancreatic adenocarcinoma

    • Stage IV disease (any T, any N, M1 [distant metastases])

    • Unresectable disease

    • Histologic diagnosis based on a metastatic site must be compatible with pancreatic cancer

    • Measurable and/or nonmeasurable disease

    • No endocrine or neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer

    • No macroscopic residual disease post-resection as the only site of disease

    • No clinically significant ascites

    • No known brain metastases

    • Patients with neurologic signs or symptoms must undergo brain imaging studies AND studies must be negative for disease

    • Zubrod performance status 0-1

    • ANC ≥ 1,500/mcL

    • Platelet count ≥ 100,000/mcL

    • Hemoglobin ≥ 9 g/dL

    • Leukocytes ≥ 3,000/mcL

    • Total bilirubin normal

    • SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN)

    • Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

    • Fasting serum glucose < 120 mg/dL or below the ULN

    • Patients with diabetes mellitus who meet this criterion must be on a stable dietary or therapeutic regimen for this condition

    • INR ≤ 1.5 and PTT ≤ 5 seconds above ULN

    • Not pregnant or nursing

    • Fertile patients must use effective contraception

    • Willing to submit previously collected tumor tissue specimens

    • No history of allergic reaction attributed to compounds of similar chemical or biological composition to anti-IGF-1R recombinant monoclonal antibody IMC-A12

    • No active acute or chronic infections requiring antibiotics

    • No significant ongoing cardiac problems, including any of the following:

    • Myocardial infarction within the past 6 months

    • Uncontrolled hypertension

    • Unstable angina

    • Uncontrolled arrhythmia

    • Congestive heart failure

    • No known HIV infection

    • No other prior malignancy, except for the following:

    • Adequately treated basal cell or squamous cell skin cancer

    • Carcinoma in situ of the cervix

    • Adequately treated stage I or II cancer from which the patient is currently in complete remission

    • Any other cancer from which the patient has been disease-free for 5 years

    • At least 14 days since prior surgery

    • At least 28 days since prior radiotherapy for palliation to metastatic sites

    • Patient must have other untreated metastatic sites that would qualify them for this protocol

    • At least 6 months since prior adjuvant chemotherapy

    • No prior chemotherapy, hormonal therapy, immunotherapy, or chemoradiotherapy for advanced or locally advanced pancreatic cancer, including drugs that target either EGFR or IGFR

    • No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other type of therapy for treatment of cancer

    • No prior gemcitabine hydrochloride

    • No prior chimerized or murine monoclonal antibody therapy

    • No concurrent CYP3A4 inducers including, but not limited to, any of the following:

    • Rifampicin

    • Rifabutin

    • Rifapentine

    • Phenytoin

    • Carbamazepine

    • Phenobarbital

    • Hypericum perforatum (St. John's wort)

    • No concurrent CYP3A4 inhibitors including, but not limited to, any of the following:

    • Atazanavir

    • Clarithromycin

    • Indinavir

    • Itraconazole

    • Ketoconazole

    • Nefazodone

    • Nelfinavir

    • Ritonavir

    • Saquinavir

    • Telithromycin

    • Troleandomycin

    • Voriconazole

    • Concurrent prophylactic low-dose coumadin or low molecular weight heparin allowed provided coagulation criteria are met

    • Full-dose anticoagulation allowed provided coagulation criteria are met and are under strict control and monitoring

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 NEA Baptist Memorial Hospital Jonesboro Arkansas United States 72401
    2 Alta Bates Summit Medical Center-Herrick Campus Berkeley California United States 94704
    3 Mills - Peninsula Hospitals Burlingame California United States 94010
    4 East Bay Radiation Oncology Center Castro Valley California United States 94546
    5 Eden Hospital Medical Center Castro Valley California United States 94546
    6 Valley Medical Oncology Consultants-Castro Valley Castro Valley California United States 94546
    7 City of Hope Medical Center Duarte California United States 91010
    8 Valley Medical Oncology Consultants-Fremont Fremont California United States 94538
    9 Glendale Memorial Hospital and Health Center Glendale California United States 91204
    10 Marin General Hospital Greenbrae California United States 94904
    11 Sutter Health Western Division Cancer Research Group Greenbrae California United States 94904
    12 University of Southern California Los Angeles California United States 90033-0804
    13 Contra Costa Regional Medical Center Martinez California United States 94553-3156
    14 El Camino Hospital Mountain View California United States 94040
    15 Highland General Hospital Oakland California United States 94602
    16 Alta Bates Summit Medical Center - Summit Campus Oakland California United States 94609
    17 Bay Area Breast Surgeons Inc Oakland California United States 94609
    18 Bay Area Tumor Institute Oakland California United States 94609
    19 Larry G Strieff MD Medical Corporation Oakland California United States 94609
    20 Tom K Lee Inc Oakland California United States 94609
    21 University of California Medical Center At Irvine-Orange Campus Orange California United States 92868
    22 Valley Care Health System - Pleasanton Pleasanton California United States 94588
    23 Valley Medical Oncology Consultants Pleasanton California United States 94588
    24 California Pacific Medical Center San Francisco California United States 94118
    25 Doctors Medical Center- JC Robinson Regional Cancer Center San Pablo California United States 94806
    26 Sutter Solano Medical Center Vallejo California United States 94589
    27 Poudre Valley Hospital Fort Collins Colorado United States 80524
    28 Piedmont Hospital Atlanta Georgia United States 30309
    29 Atlanta Regional CCOP Atlanta Georgia United States 30342
    30 Northside Hospital Atlanta Georgia United States 30342
    31 Saint Joseph's Hospital of Atlanta Atlanta Georgia United States 30342
    32 Well Star Cobb Hospital Austell Georgia United States 30106
    33 John B Amos Cancer Center Columbus Georgia United States 31904
    34 Dekalb Medical Center Decatur Georgia United States 30033
    35 Gwinnett Medical Center Lawrenceville Georgia United States 30045
    36 Wellstar Kennestone Hospital Marietta Georgia United States 30060
    37 Southern Regional Medical Center Riverdale Georgia United States 30274
    38 Harbin Clinic Medical Oncology and Clinical Research Rome Georgia United States 30165
    39 Memorial Health University Medical Center Savannah Georgia United States 31403
    40 Saint Joseph's-Candler Health System Savannah Georgia United States 31405
    41 South Georgia Medical Center Valdosta Georgia United States 31603
    42 Cancer Care Center of Decatur Decatur Illinois United States 62526
    43 Decatur Memorial Hospital Decatur Illinois United States 62526
    44 Crossroads Cancer Center Effingham Illinois United States 62401
    45 Menorah Medical Center Overland Park Kansas United States 66209
    46 Saint Luke's South Hospital Overland Park Kansas United States 66213
    47 Shawnee Mission Medical Center Shawnee Mission Kansas United States 66204
    48 Christus Saint Frances Cabrini Hospital Alexandria Louisiana United States 71301
    49 Sinai Hospital of Baltimore Baltimore Maryland United States 21215
    50 Boston Medical Center Boston Massachusetts United States 02118
    51 Bronson Battle Creek Battle Creek Michigan United States 49017
    52 Mecosta County Medical Center Big Rapids Michigan United States 49307
    53 Wayne State University Detroit Michigan United States 48202
    54 Grand Rapids Clinical Oncology Program Grand Rapids Michigan United States 49503
    55 Saint Mary's Health Care Grand Rapids Michigan United States 49503
    56 Spectrum Health at Butterworth Campus Grand Rapids Michigan United States 49503
    57 Mercy Health Partners-Mercy Campus Muskegon Michigan United States 49444
    58 William Beaumont Hospital Royal Oak Michigan United States 48073
    59 Munson Medical Center Traverse City Michigan United States 49684
    60 Metro Health Hospital Wyoming Michigan United States 49519
    61 University of Mississippi Medical Center Jackson Mississippi United States 39216
    62 Truman Medical Center Kansas City Missouri United States 64108
    63 Saint Luke's Cancer Institute Kansas City Missouri United States 64111
    64 Saint Luke's Hospital of Kansas City Kansas City Missouri United States 64111
    65 Saint Joseph Health Center Kansas City Missouri United States 64114
    66 North Kansas City Hospital Kansas City Missouri United States 64116
    67 Heartland Hematology and Oncology Associates Incorporated Kansas City Missouri United States 64118
    68 Research Medical Center Kansas City Missouri United States 64132
    69 Saint Luke's East - Lee's Summit Lee's Summit Missouri United States 64086
    70 Liberty Hospital Liberty Missouri United States 64068
    71 Liberty Radiation Oncology Clinic Liberty Missouri United States 64068
    72 Heartland Regional Medical Center Saint Joseph Missouri United States 64506
    73 Saint Joseph Oncology Inc Saint Joseph Missouri United States 64507
    74 Saint Louis University Hospital Saint Louis Missouri United States 63110
    75 Montana Cancer Consortium CCOP Billings Montana United States 59101
    76 Northern Rockies Radiation Oncology Center Billings Montana United States 59101
    77 Saint Vincent Healthcare Billings Montana United States 59101
    78 Hematology-Oncology Centers of the Northern Rockies PC Billings Montana United States 59102
    79 Billings Clinic Billings Montana United States 59107-7000
    80 Bozeman Deaconess Cancer Center Bozeman Montana United States 59715
    81 Bozeman Deaconess Hospital Bozeman Montana United States 59715
    82 Saint James Community Hospital and Cancer Treatment Center Butte Montana United States 59701
    83 Benefis Healthcare- Sletten Cancer Institute Great Falls Montana United States 59405
    84 Berdeaux, Donald MD (UIA Investigator) Great Falls Montana United States 59405
    85 Great Falls Clinic Great Falls Montana United States 59405
    86 Northern Montana Hospital Havre Montana United States 59501
    87 Saint Peter's Community Hospital Helena Montana United States 59601
    88 Glacier Oncology PLLC Kalispell Montana United States 59901
    89 Kalispell Medical Oncology Kalispell Montana United States 59901
    90 Kalispell Regional Medical Center Kalispell Montana United States 59901
    91 Community Medical Hospital Missoula Montana United States 59801
    92 Montana Cancer Specialists Missoula Montana United States 59802
    93 Saint Patrick Hospital - Community Hospital Missoula Montana United States 59802
    94 Guardian Oncology and Center for Wellness Missoula Montana United States 59804
    95 University of New Mexico Cancer Center Albuquerque New Mexico United States 87106
    96 Arnot Ogden Medical Center Elmira New York United States 14905
    97 Highland Hospital Rochester New York United States 14620
    98 Interlakes Foundation Inc-Rochester Rochester New York United States 14623
    99 University of Rochester Rochester New York United States 14642
    100 Randolph Hospital Asheboro North Carolina United States 27203
    101 Carolinas Medical Center Charlotte North Carolina United States 28203
    102 Presbyterian Hospital Charlotte North Carolina United States 28204
    103 Wayne Memorial Hospital Goldsboro North Carolina United States 27534
    104 Cone Health Cancer Center Greensboro North Carolina United States 27403
    105 Margaret R Pardee Memorial Hospital Hendersonville North Carolina United States 28791
    106 Annie Penn Memorial Hospital Reidsville North Carolina United States 27320
    107 Akron General Medical Center Akron Ohio United States 44307
    108 Veterans Administration Medical Center - Cincinnati Cincinnati Ohio United States 45220
    109 University of Cincinnati Cincinnati Ohio United States 45267
    110 Medical University of South Carolina Charleston South Carolina United States 29425
    111 The Don and Sybil Harrington Cancer Center Amarillo Texas United States 79106
    112 University of Texas Medical Branch at Galveston Galveston Texas United States 77555-0565
    113 Baylor College of Medicine Houston Texas United States 77030
    114 Ben Taub General Hospital Houston Texas United States 77030
    115 Methodist Hospital Houston Texas United States 77030
    116 Saint Luke's Episcopal Hospital Houston Texas United States 77030
    117 Veterans Administration Medical Center Houston Texas United States 77030
    118 Scott and White Memorial Hospital Temple Texas United States 76508
    119 American Fork Hospital American Fork Utah United States 84003
    120 Sandra L Maxwell Cancer Center Cedar City Utah United States 84720
    121 Logan Regional Hospital Logan Utah United States 84321
    122 Intermountain Medical Center Murray Utah United States 84157
    123 McKay-Dee Hospital Center Ogden Utah United States 84403
    124 Utah Valley Regional Medical Center Provo Utah United States 84604-3337
    125 Dixie Medical Center Regional Cancer Center Saint George Utah United States 84770
    126 Intermountain Health Care Salt Lake City Utah United States 84103
    127 Utah Cancer Specialists-Salt Lake City Salt Lake City Utah United States 84106
    128 LDS Hospital Salt Lake City Utah United States 84143
    129 Memorial Hospital Of Martinsville Martinsville Virginia United States 24115
    130 PeaceHealth Saint Joseph Medical Center Bellingham Washington United States 98225
    131 Harrison Bremerton Hematology and Oncology Bremerton Washington United States 98310
    132 Columbia Basin Hematology and Oncology PLLC Kennewick Washington United States 99336
    133 Skagit Valley Hospital Mount Vernon Washington United States 98274
    134 Harrison Poulsbo Hematology and Oncology Poulsbo Washington United States 98370
    135 Harborview Medical Center Seattle Washington United States 98104
    136 Minor and James Medical PLLC Seattle Washington United States 98104
    137 Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle Washington United States 98109
    138 Group Health Cooperative Seattle Washington United States 98112
    139 Swedish Medical Center-First Hill Seattle Washington United States 98122-4307
    140 The Polyclinic Seattle Washington United States 98122
    141 University of Washington Medical Center Seattle Washington United States 98195
    142 Cancer Care Northwest - Spokane South Spokane Washington United States 99202
    143 Evergreen Hematology and Oncology PS Spokane Washington United States 99218
    144 Wenatchee Valley Medical Center Wenatchee Washington United States 98801
    145 Rocky Mountain Oncology Casper Wyoming United States 82609
    146 Welch Cancer Center Sheridan Wyoming United States 82801

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Philip Philip, Southwest Oncology Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00617708
    Other Study ID Numbers:
    • NCI-2009-00797
    • NCI-2009-00797
    • CDR0000586427
    • SWOG-S0727
    • S0727
    • S0727
    • U10CA032102
    First Posted:
    Feb 18, 2008
    Last Update Posted:
    Feb 8, 2022
    Last Verified:
    Jan 1, 2022

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Ph I: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine
    Arm/Group Description Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days.
    Period Title: Overall Study
    STARTED 10 60 64
    Eligible and Began Protocol Therapy 9 57 59
    COMPLETED 0 0 0
    NOT COMPLETED 10 60 64

    Baseline Characteristics

    Arm/Group Title Ph I: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine Total
    Arm/Group Description Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days. Total of all reporting groups
    Overall Participants 9 57 59 125
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    61
    63
    64
    63
    Sex: Female, Male (Count of Participants)
    Female
    3
    33.3%
    34
    59.6%
    25
    42.4%
    62
    49.6%
    Male
    6
    66.7%
    23
    40.4%
    34
    57.6%
    63
    50.4%
    Race/Ethnicity, Customized (participants) [Number]
    White
    5
    55.6%
    44
    77.2%
    51
    86.4%
    100
    80%
    Black
    2
    22.2%
    10
    17.5%
    6
    10.2%
    18
    14.4%
    Asian
    1
    11.1%
    2
    3.5%
    2
    3.4%
    5
    4%
    Unknown
    1
    11.1%
    1
    1.8%
    0
    0%
    2
    1.6%
    Race/Ethnicity, Customized (participants) [Number]
    Hispanic
    1
    11.1%
    3
    5.3%
    5
    8.5%
    9
    7.2%
    Non-Hispanic
    8
    88.9%
    53
    93%
    47
    79.7%
    108
    86.4%
    Unknown
    0
    0%
    1
    1.8%
    7
    11.9%
    8
    6.4%

    Outcome Measures

    1. Secondary Outcome
    Title Overall Survival
    Description From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    Eligible patients in the Phase II portion of the study.
    Arm/Group Title Erlotinib + Gemcitabine + IMC-A12 Erlotinib + Gemcitabine
    Arm/Group Description Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days.
    Measure Participants 57 59
    Median (95% Confidence Interval) [months]
    7.0
    6.5
    2. Primary Outcome
    Title Maximum Tolerated Dose Determination
    Description Maximum dose of IMC-A12 (in combination with erlotinib and gemcitabine) at which 3/10 or fewer patients have dose-limiting toxicities (DLT). Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0). DLT apply only during cycle 1 and should be drug-related (possible, probable, or definite).
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    Phase I patients receiving at least three doses of the assigned dose during Cycle 1 or whom developed a DLT.
    Arm/Group Title Ph I: Erlotinib + Gemcitabine + IMC-A12
    Arm/Group Description Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days.
    Measure Participants 10
    Number [mg/kg IMC-A12]
    6
    3. Secondary Outcome
    Title Response
    Description Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    Eligible patients in the Phase II portion of the study with measurable disease and adequate response assessment.
    Arm/Group Title Erlotinib + Gemcitabine + IMC-A12 Erlotinib + Gemcitabine
    Arm/Group Description Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days.
    Measure Participants 51 53
    Number (95% Confidence Interval) [percentage of participants]
    13.7
    152.2%
    15.3
    26.8%
    4. Secondary Outcome
    Title Toxicity
    Description Number of patients with Grade 3 through 5 adverse events that are related to study drug. Only adverse events that are possibly, probably or definitely related to study drug are reported.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    Eligible patients who received any treatment and were assessed for toxicity were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.
    Arm/Group Title Ph I: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine
    Arm/Group Description Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days.
    Measure Participants 9 57 57
    ALT, SGPT (serum glutamic pyruvic transaminase)
    0
    0%
    9
    15.8%
    4
    6.8%
    AST, SGOT
    0
    0%
    6
    10.5%
    3
    5.1%
    Acidosis (metabolic or respiratory)
    0
    0%
    1
    1.8%
    0
    0%
    Adult respiratory distress syndrome (ARDS)
    0
    0%
    0
    0%
    1
    1.7%
    Albumin, serum-low (hypoalbuminemia)
    0
    0%
    3
    5.3%
    0
    0%
    Alkaline phosphatase
    0
    0%
    4
    7%
    3
    5.1%
    Allergic reaction/hypersensitivity
    1
    11.1%
    0
    0%
    0
    0%
    Anorexia
    1
    11.1%
    7
    12.3%
    6
    10.2%
    Bilirubin (hyperbilirubinemia)
    0
    0%
    5
    8.8%
    0
    0%
    Calcium, serum-low (hypocalcemia)
    0
    0%
    1
    1.8%
    1
    1.7%
    Cardiac troponin I (cTnI)
    0
    0%
    3
    5.3%
    0
    0%
    Cardiac-ischemia/infarction
    0
    0%
    0
    0%
    1
    1.7%
    Cardiopulmonary arrest, cause unknown (non-fatal)
    0
    0%
    0
    0%
    1
    1.7%
    Dehydration
    3
    33.3%
    6
    10.5%
    5
    8.5%
    Diarrhea
    2
    22.2%
    3
    5.3%
    2
    3.4%
    Dizziness
    0
    0%
    1
    1.8%
    0
    0%
    Dysphagia (difficulty swallowing)
    0
    0%
    0
    0%
    1
    1.7%
    Dyspnea (shortness of breath)
    0
    0%
    2
    3.5%
    4
    6.8%
    Edema: limb
    0
    0%
    0
    0%
    1
    1.7%
    Edema: trunk/genital
    0
    0%
    0
    0%
    1
    1.7%
    Fatigue (asthenia, lethargy, malaise)
    4
    44.4%
    16
    28.1%
    12
    20.3%
    GGT (gamma-glutamyl transpeptidase)
    0
    0%
    1
    1.8%
    0
    0%
    Glucose, serum-high (hyperglycemia)
    2
    22.2%
    16
    28.1%
    1
    1.7%
    Hemoglobin
    0
    0%
    9
    15.8%
    8
    13.6%
    Hypotension
    0
    0%
    3
    5.3%
    1
    1.7%
    Hypoxia
    0
    0%
    1
    1.8%
    2
    3.4%
    Inf (clin/microbio) w/Gr 3-4 neuts - Blood
    0
    0%
    0
    0%
    1
    1.7%
    Inf (clin/microbio) w/Gr 3-4 neuts - UTI
    0
    0%
    0
    0%
    1
    1.7%
    Inf w/normal ANC or Gr 1-2 neutrophils - Bil. tree
    0
    0%
    1
    1.8%
    0
    0%
    Inf w/normal ANC or Gr 1-2 neutrophils - Blood
    1
    11.1%
    0
    0%
    1
    1.7%
    Inf w/normal ANC or Gr 1-2 neutrophils - Lung
    0
    0%
    1
    1.8%
    2
    3.4%
    Inf w/normal ANC or Gr 1-2 neutrophils - Pancreas
    0
    0%
    0
    0%
    1
    1.7%
    Inf w/normal ANC or Gr 1-2 neutrophils - Skin
    0
    0%
    1
    1.8%
    0
    0%
    Inf w/normal ANC or Gr 1-2 neutrophils - UTI
    0
    0%
    0
    0%
    1
    1.7%
    Inf w/normal ANC or Gr 1-2 neutrophils -Up aerodig
    0
    0%
    1
    1.8%
    0
    0%
    Infection-Other (Specify)
    0
    0%
    1
    1.8%
    0
    0%
    Left ventricular systolic dysfunction
    0
    0%
    1
    1.8%
    0
    0%
    Leukocytes (total WBC)
    1
    11.1%
    9
    15.8%
    5
    8.5%
    Liver dysfunction/failure (clinical)
    0
    0%
    0
    0%
    1
    1.7%
    Lymphatics-Other (Specify)
    0
    0%
    0
    0%
    1
    1.7%
    Lymphopenia
    1
    11.1%
    4
    7%
    5
    8.5%
    Magnesium, serum-low (hypomagnesemia)
    0
    0%
    1
    1.8%
    0
    0%
    Mucositis/stomatitis (functional/symp) - Oral cav
    0
    0%
    1
    1.8%
    0
    0%
    Muscle weakness, not d/t neuropathy - Extrem-lower
    0
    0%
    1
    1.8%
    0
    0%
    Muscle weakness, not d/t neuropathy - body/general
    0
    0%
    5
    8.8%
    3
    5.1%
    Nausea
    4
    44.4%
    9
    15.8%
    6
    10.2%
    Neuropathy: sensory
    0
    0%
    1
    1.8%
    0
    0%
    Neutrophils/granulocytes (ANC/AGC)
    3
    33.3%
    21
    36.8%
    10
    16.9%
    Obstruction, GI - Duodenum
    0
    0%
    0
    0%
    1
    1.7%
    Opportunistic inf associated w/gt=Gr 2 lymphopenia
    1
    11.1%
    0
    0%
    0
    0%
    PTT (Partial thromboplastin time)
    0
    0%
    1
    1.8%
    0
    0%
    Pain - Abdomen NOS
    0
    0%
    0
    0%
    1
    1.7%
    Pain - Eye
    0
    0%
    1
    1.8%
    0
    0%
    Pain - Head/headache
    0
    0%
    1
    1.8%
    0
    0%
    Pain - Muscle
    0
    0%
    0
    0%
    1
    1.7%
    Pancreas, exocrine enzyme deficiency
    0
    0%
    1
    1.8%
    0
    0%
    Pancreatic endocrine: glucose intolerance
    0
    0%
    6
    10.5%
    0
    0%
    Pericardial effusion (non-malignant)
    0
    0%
    0
    0%
    1
    1.7%
    Personality/behavioral
    0
    0%
    1
    1.8%
    0
    0%
    Platelets
    2
    22.2%
    16
    28.1%
    7
    11.9%
    Pleural effusion (non-malignant)
    0
    0%
    0
    0%
    1
    1.7%
    Pneumonitis/pulmonary infiltrates
    0
    0%
    1
    1.8%
    2
    3.4%
    Potassium, serum-low (hypokalemia)
    0
    0%
    1
    1.8%
    1
    1.7%
    Pulmonary/Upper Respiratory-Other (Specify)
    0
    0%
    1
    1.8%
    1
    1.7%
    Rash/desquamation
    0
    0%
    0
    0%
    1
    1.7%
    Rash: acne/acneiform
    0
    0%
    3
    5.3%
    2
    3.4%
    Rash: erythema multiforme
    0
    0%
    1
    1.8%
    0
    0%
    SVT and nodal arrhythmia - Atrial fibrillation
    0
    0%
    1
    1.8%
    0
    0%
    Sodium, serum-low (hyponatremia)
    1
    11.1%
    5
    8.8%
    1
    1.7%
    Stricture/stenosis (incl anastomotic), Stomach
    0
    0%
    0
    0%
    1
    1.7%
    Syncope (fainting)
    0
    0%
    3
    5.3%
    0
    0%
    Thrombosis/embolism (vascular access-related)
    0
    0%
    1
    1.8%
    0
    0%
    Thrombosis/thrombus/embolism
    0
    0%
    4
    7%
    1
    1.7%
    Tremor
    0
    0%
    1
    1.8%
    0
    0%
    Uric acid, serum-high (hyperuricemia)
    0
    0%
    1
    1.8%
    0
    0%
    Ventricular arrhythmia - Ventricular fibrillation
    0
    0%
    1
    1.8%
    0
    0%
    Vision-blurred vision
    0
    0%
    1
    1.8%
    0
    0%
    Vision-photophobia
    0
    0%
    1
    1.8%
    0
    0%
    Vomiting
    2
    22.2%
    5
    8.8%
    1
    1.7%
    Weight loss
    0
    0%
    2
    3.5%
    0
    0%
    5. Primary Outcome
    Title Progression-Free Survival
    Description From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    Eligible patients in the Phase II portion of the study.
    Arm/Group Title Erlotinib + Gemcitabine + IMC-A12 Erlotinib + Gemcitabine
    Arm/Group Description Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days.
    Measure Participants 57 59
    Median (95% Confidence Interval) [months]
    3.6
    3.6

    Adverse Events

    Time Frame Up to 3 years
    Adverse Event Reporting Description
    Arm/Group Title Ph I: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine
    Arm/Group Description Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days.
    All Cause Mortality
    Ph I: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Ph I: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/9 (55.6%) 34/57 (59.6%) 33/57 (57.9%)
    Blood and lymphatic system disorders
    Hemoglobin 0/9 (0%) 6/57 (10.5%) 2/57 (3.5%)
    Lymphatics-Other (Specify) 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Cardiac disorders
    Atrioventricular block - first degree 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Cardiac-ischemia/infarction 0/9 (0%) 1/57 (1.8%) 2/57 (3.5%)
    Left ventricular systolic dysfunction 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Pericardial effusion (non-malignant) 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    SVT and nodal arrhythmia - Atrial fibrillation 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Ventricular arrhythmia - Ventricular fibrillation 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Gastrointestinal disorders
    Ascites (non-malignant) 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Constipation 0/9 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Diarrhea 1/9 (11.1%) 1/57 (1.8%) 0/57 (0%)
    Distention/bloating, abdominal 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Gastrointestinal-Other (Specify) 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Hemorrhage, GI - Duodenum 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Hemorrhage, GI - Rectum 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Hemorrhage, GI - Upper GI NOS 0/9 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Ileus, GI (functional obstruction of bowel) 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Incontinence, anal 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Nausea 3/9 (33.3%) 3/57 (5.3%) 3/57 (5.3%)
    Obstruction, GI - Duodenum 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Obstruction, GI - Small bowel NOS 1/9 (11.1%) 0/57 (0%) 1/57 (1.8%)
    Obstruction, GI - Stomach 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Pain - Abdomen NOS 0/9 (0%) 9/57 (15.8%) 3/57 (5.3%)
    Vomiting 2/9 (22.2%) 4/57 (7%) 3/57 (5.3%)
    General disorders
    Death not associated with CTCAE term - Death NOS 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Edema: limb 0/9 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Fatigue (asthenia, lethargy, malaise) 1/9 (11.1%) 3/57 (5.3%) 4/57 (7%)
    Hepatobiliary disorders
    Hepatobiliary/Pancreas-Other (Specify) 0/9 (0%) 2/57 (3.5%) 0/57 (0%)
    Liver dysfunction/failure (clinical) 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Portal vein flow 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Stricture/stenosis (incl anastomotic)-Biliary tree 0/9 (0%) 0/57 (0%) 2/57 (3.5%)
    Immune system disorders
    Allergic reaction/hypersensitivity 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Infections and infestations
    Inf (clin/microbio) w/Gr 3-4 neuts - Blood 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Ab NOS 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Bil. tree 0/9 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Blood 1/9 (11.1%) 0/57 (0%) 1/57 (1.8%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Catheter 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Lung 0/9 (0%) 1/57 (1.8%) 2/57 (3.5%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Pancreas 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Perit cav 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Skin 0/9 (0%) 2/57 (3.5%) 1/57 (1.8%)
    Inf w/normal ANC or Gr 1-2 neutrophils - UTI 0/9 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Up airway 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils -Up aerodig 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils-Foreign bod 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Infection with unknown ANC - Blood 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Injury, poisoning and procedural complications
    Fracture 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Thrombosis/embolism (vascular access-related) 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Investigations
    ALT, SGPT (serum glutamic pyruvic transaminase) 0/9 (0%) 1/57 (1.8%) 1/57 (1.8%)
    AST, SGOT 0/9 (0%) 1/57 (1.8%) 2/57 (3.5%)
    Alkaline phosphatase 0/9 (0%) 1/57 (1.8%) 2/57 (3.5%)
    Amylase 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Bilirubin (hyperbilirubinemia) 0/9 (0%) 5/57 (8.8%) 2/57 (3.5%)
    Cardiac troponin I (cTnI) 0/9 (0%) 2/57 (3.5%) 1/57 (1.8%)
    Creatinine 1/9 (11.1%) 1/57 (1.8%) 0/57 (0%)
    Lipase 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Lymphopenia 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Pancreas, exocrine enzyme deficiency 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Platelets 0/9 (0%) 2/57 (3.5%) 0/57 (0%)
    Weight loss 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Metabolism and nutrition disorders
    Acidosis (metabolic or respiratory) 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Albumin, serum-low (hypoalbuminemia) 0/9 (0%) 3/57 (5.3%) 0/57 (0%)
    Anorexia 0/9 (0%) 1/57 (1.8%) 2/57 (3.5%)
    Calcium, serum-low (hypocalcemia) 0/9 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Dehydration 4/9 (44.4%) 6/57 (10.5%) 5/57 (8.8%)
    Glucose, serum-high (hyperglycemia) 0/9 (0%) 4/57 (7%) 1/57 (1.8%)
    Potassium, serum-low (hypokalemia) 0/9 (0%) 1/57 (1.8%) 2/57 (3.5%)
    Sodium, serum-low (hyponatremia) 0/9 (0%) 3/57 (5.3%) 0/57 (0%)
    Uric acid, serum-high (hyperuricemia) 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis (non-septic) 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Muscle weakness, not d/t neuropathy - body/general 0/9 (0%) 5/57 (8.8%) 1/57 (1.8%)
    Pain - Back 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Pain - Muscle 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Death - Disease progression NOS 1/9 (11.1%) 9/57 (15.8%) 10/57 (17.5%)
    Pain - Tumor pain 0/9 (0%) 3/57 (5.3%) 1/57 (1.8%)
    Nervous system disorders
    CNS cerebrovascular ischemia 0/9 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Dizziness 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Neuropathy: motor 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Syncope (fainting) 0/9 (0%) 2/57 (3.5%) 0/57 (0%)
    Psychiatric disorders
    Confusion 1/9 (11.1%) 2/57 (3.5%) 0/57 (0%)
    Mood alteration - agitation 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Personality/behavioral 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Psychosis (hallucinations/delusions) 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Renal and urinary disorders
    Incontinence, urinary 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome (ARDS) 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Dyspnea (shortness of breath) 0/9 (0%) 2/57 (3.5%) 5/57 (8.8%)
    Hypoxia 0/9 (0%) 1/57 (1.8%) 3/57 (5.3%)
    Pleural effusion (non-malignant) 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Pneumonitis/pulmonary infiltrates 0/9 (0%) 1/57 (1.8%) 3/57 (5.3%)
    Pulmonary/Upper Respiratory-Other (Specify) 0/9 (0%) 1/57 (1.8%) 1/57 (1.8%)
    Skin and subcutaneous tissue disorders
    Rash/desquamation 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Rash: acne/acneiform 0/9 (0%) 0/57 (0%) 1/57 (1.8%)
    Skin breakdown/decubitus ulcer 0/9 (0%) 1/57 (1.8%) 0/57 (0%)
    Vascular disorders
    Hypotension 0/9 (0%) 2/57 (3.5%) 3/57 (5.3%)
    Thrombosis/thrombus/embolism 0/9 (0%) 5/57 (8.8%) 3/57 (5.3%)
    Other (Not Including Serious) Adverse Events
    Ph I: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine + IMC-A12 Ph II: Erlotinib + Gemcitabine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/9 (100%) 56/57 (98.2%) 57/57 (100%)
    Blood and lymphatic system disorders
    Hemoglobin 8/9 (88.9%) 38/57 (66.7%) 39/57 (68.4%)
    Cardiac disorders
    Cardiac Arrhythmia-Other (Specify) 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Cardiac-ischemia/infarction 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    SVT and nodal arrhythmia - Atrial tachycardia/PAT 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    SVT and nodal arrhythmia - Sinus bradycardia 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Ear and labyrinth disorders
    Auditory/Ear-Other (Specify) 2/9 (22.2%) 0/57 (0%) 0/57 (0%)
    Eye disorders
    Dry eye syndrome 1/9 (11.1%) 4/57 (7%) 0/57 (0%)
    Ocular/Visual-Other (Specify) 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Vision-blurred vision 0/9 (0%) 5/57 (8.8%) 4/57 (7%)
    Vision-flashing lights/floaters 3/9 (33.3%) 3/57 (5.3%) 0/57 (0%)
    Gastrointestinal disorders
    Constipation 7/9 (77.8%) 33/57 (57.9%) 27/57 (47.4%)
    Diarrhea 5/9 (55.6%) 32/57 (56.1%) 27/57 (47.4%)
    Distention/bloating, abdominal 0/9 (0%) 0/57 (0%) 3/57 (5.3%)
    Dry mouth/salivary gland (xerostomia) 1/9 (11.1%) 6/57 (10.5%) 5/57 (8.8%)
    Flatulence 0/9 (0%) 3/57 (5.3%) 5/57 (8.8%)
    Gastrointestinal-Other (Specify) 0/9 (0%) 3/57 (5.3%) 5/57 (8.8%)
    Heartburn/dyspepsia 3/9 (33.3%) 10/57 (17.5%) 4/57 (7%)
    Hemorrhage, GI - Abdomen NOS 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Hemorrhoids 1/9 (11.1%) 4/57 (7%) 0/57 (0%)
    Malabsorption 0/9 (0%) 0/57 (0%) 3/57 (5.3%)
    Mucositis/stomatitis (clinical exam) - Oral cavity 1/9 (11.1%) 17/57 (29.8%) 0/57 (0%)
    Mucositis/stomatitis (functional/symp) - Oral cav 2/9 (22.2%) 10/57 (17.5%) 4/57 (7%)
    Nausea 9/9 (100%) 43/57 (75.4%) 34/57 (59.6%)
    Obstruction, GI - Small bowel NOS 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Pain - Abdomen NOS 5/9 (55.6%) 17/57 (29.8%) 21/57 (36.8%)
    Pain - Oral cavity 0/9 (0%) 4/57 (7%) 0/57 (0%)
    Pain - Rectum 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Pain - Stomach 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Vomiting 6/9 (66.7%) 26/57 (45.6%) 25/57 (43.9%)
    General disorders
    Edema: limb 1/9 (11.1%) 12/57 (21.1%) 16/57 (28.1%)
    Fatigue (asthenia, lethargy, malaise) 8/9 (88.9%) 47/57 (82.5%) 43/57 (75.4%)
    Fever in absence of neutropenia, ANC lt1.0x10e9/L 3/9 (33.3%) 5/57 (8.8%) 15/57 (26.3%)
    Pain - Chest/thorax NOS 0/9 (0%) 3/57 (5.3%) 0/57 (0%)
    Pain-Other (Specify) 0/9 (0%) 7/57 (12.3%) 3/57 (5.3%)
    Rigors/chills 1/9 (11.1%) 5/57 (8.8%) 7/57 (12.3%)
    Immune system disorders
    Allergic reaction/hypersensitivity 0/9 (0%) 0/57 (0%) 3/57 (5.3%)
    Allergy/Immunology-Other (Specify) 0/9 (0%) 3/57 (5.3%) 0/57 (0%)
    Infections and infestations
    Inf w/normal ANC or Gr 1-2 neutrophils - Ab NOS 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Skin 2/9 (22.2%) 3/57 (5.3%) 0/57 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - UTI 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Inf w/normal ANC or Gr 1-2 neutrophils - Up airway 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Infection-Other (Specify) 0/9 (0%) 3/57 (5.3%) 3/57 (5.3%)
    Opportunistic inf associated w/gt=Gr 2 lymphopenia 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Injury, poisoning and procedural complications
    Bruising (in absence of Gr 3-4 thrombocytopenia) 2/9 (22.2%) 0/57 (0%) 0/57 (0%)
    Investigations
    ALT, SGPT (serum glutamic pyruvic transaminase) 8/9 (88.9%) 34/57 (59.6%) 30/57 (52.6%)
    AST, SGOT 8/9 (88.9%) 36/57 (63.2%) 31/57 (54.4%)
    Alkaline phosphatase 5/9 (55.6%) 35/57 (61.4%) 25/57 (43.9%)
    Bilirubin (hyperbilirubinemia) 3/9 (33.3%) 18/57 (31.6%) 18/57 (31.6%)
    Creatinine 3/9 (33.3%) 9/57 (15.8%) 8/57 (14%)
    INR (of prothrombin time) 0/9 (0%) 4/57 (7%) 7/57 (12.3%)
    Leukocytes (total WBC) 4/9 (44.4%) 29/57 (50.9%) 29/57 (50.9%)
    Lymphopenia 1/9 (11.1%) 8/57 (14%) 10/57 (17.5%)
    Metabolic/Laboratory-Other (Specify) 0/9 (0%) 5/57 (8.8%) 4/57 (7%)
    Neutrophils/granulocytes (ANC/AGC) 6/9 (66.7%) 30/57 (52.6%) 20/57 (35.1%)
    PTT (Partial thromboplastin time) 0/9 (0%) 3/57 (5.3%) 4/57 (7%)
    Platelets 9/9 (100%) 42/57 (73.7%) 36/57 (63.2%)
    Weight loss 3/9 (33.3%) 27/57 (47.4%) 25/57 (43.9%)
    Metabolism and nutrition disorders
    Albumin, serum-low (hypoalbuminemia) 2/9 (22.2%) 25/57 (43.9%) 18/57 (31.6%)
    Anorexia 5/9 (55.6%) 35/57 (61.4%) 31/57 (54.4%)
    Calcium, serum-high (hypercalcemia) 2/9 (22.2%) 0/57 (0%) 0/57 (0%)
    Calcium, serum-low (hypocalcemia) 2/9 (22.2%) 18/57 (31.6%) 14/57 (24.6%)
    Dehydration 2/9 (22.2%) 12/57 (21.1%) 11/57 (19.3%)
    Glucose, serum-high (hyperglycemia) 9/9 (100%) 27/57 (47.4%) 29/57 (50.9%)
    Glucose, serum-low (hypoglycemia) 0/9 (0%) 7/57 (12.3%) 4/57 (7%)
    Magnesium, serum-low (hypomagnesemia) 2/9 (22.2%) 5/57 (8.8%) 5/57 (8.8%)
    Pancreatic endocrine: glucose intolerance 0/9 (0%) 7/57 (12.3%) 0/57 (0%)
    Phosphate, serum-low (hypophosphatemia) 2/9 (22.2%) 4/57 (7%) 0/57 (0%)
    Potassium, serum-high (hyperkalemia) 2/9 (22.2%) 11/57 (19.3%) 4/57 (7%)
    Potassium, serum-low (hypokalemia) 1/9 (11.1%) 10/57 (17.5%) 15/57 (26.3%)
    Sodium, serum-low (hyponatremia) 3/9 (33.3%) 19/57 (33.3%) 19/57 (33.3%)
    Musculoskeletal and connective tissue disorders
    Muscle weakness, not d/t neuropathy - Extrem-lower 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Muscle weakness, not d/t neuropathy - body/general 2/9 (22.2%) 10/57 (17.5%) 9/57 (15.8%)
    Pain - Back 2/9 (22.2%) 13/57 (22.8%) 8/57 (14%)
    Pain - Extremity-limb 0/9 (0%) 3/57 (5.3%) 0/57 (0%)
    Pain - Joint 3/9 (33.3%) 7/57 (12.3%) 3/57 (5.3%)
    Pain - Muscle 1/9 (11.1%) 3/57 (5.3%) 0/57 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pain - Tumor pain 3/9 (33.3%) 6/57 (10.5%) 7/57 (12.3%)
    Nervous system disorders
    Dizziness 2/9 (22.2%) 8/57 (14%) 7/57 (12.3%)
    Neuropathy: sensory 1/9 (11.1%) 9/57 (15.8%) 4/57 (7%)
    Ocular/Visual-Other (Specify) 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Pain - Head/headache 1/9 (11.1%) 6/57 (10.5%) 0/57 (0%)
    Syncope (fainting) 0/9 (0%) 3/57 (5.3%) 0/57 (0%)
    Taste alteration (dysgeusia) 3/9 (33.3%) 21/57 (36.8%) 16/57 (28.1%)
    Tremor 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Psychiatric disorders
    Confusion 1/9 (11.1%) 3/57 (5.3%) 0/57 (0%)
    Insomnia 2/9 (22.2%) 10/57 (17.5%) 12/57 (21.1%)
    Mood alteration - agitation 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Mood alteration - anxiety 1/9 (11.1%) 11/57 (19.3%) 8/57 (14%)
    Mood alteration - depression 3/9 (33.3%) 8/57 (14%) 5/57 (8.8%)
    Renal and urinary disorders
    Hemorrhage, GU - Urinary NOS 0/9 (0%) 0/57 (0%) 3/57 (5.3%)
    Renal failure 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Urinary frequency/urgency 0/9 (0%) 5/57 (8.8%) 0/57 (0%)
    Urinary retention (including neurogenic bladder) 0/9 (0%) 0/57 (0%) 4/57 (7%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 0/9 (0%) 4/57 (7%) 0/57 (0%)
    Cough 2/9 (22.2%) 12/57 (21.1%) 8/57 (14%)
    Dyspnea (shortness of breath) 2/9 (22.2%) 15/57 (26.3%) 20/57 (35.1%)
    Hemorrhage, pulmonary/upper respiratory - Nose 1/9 (11.1%) 9/57 (15.8%) 0/57 (0%)
    Mucositis/stomatitis (clinical exam) - Pharynx 2/9 (22.2%) 0/57 (0%) 0/57 (0%)
    Nasal cavity/paranasal sinus reactions 1/9 (11.1%) 0/57 (0%) 0/57 (0%)
    Pleural effusion (non-malignant) 0/9 (0%) 0/57 (0%) 4/57 (7%)
    Voice changes/dysarthria 0/9 (0%) 4/57 (7%) 0/57 (0%)
    Skin and subcutaneous tissue disorders
    Dermatology/Skin-Other (Specify) 0/9 (0%) 5/57 (8.8%) 0/57 (0%)
    Dry skin 6/9 (66.7%) 13/57 (22.8%) 10/57 (17.5%)
    Hair loss/Alopecia (scalp or body) 1/9 (11.1%) 4/57 (7%) 10/57 (17.5%)
    Nail changes 0/9 (0%) 8/57 (14%) 0/57 (0%)
    Pruritus/itching 2/9 (22.2%) 12/57 (21.1%) 4/57 (7%)
    Rash/desquamation 2/9 (22.2%) 14/57 (24.6%) 22/57 (38.6%)
    Rash: acne/acneiform 6/9 (66.7%) 31/57 (54.4%) 24/57 (42.1%)
    Rash: hand-foot skin reaction 0/9 (0%) 4/57 (7%) 0/57 (0%)
    Sweating (diaphoresis) 1/9 (11.1%) 6/57 (10.5%) 6/57 (10.5%)
    Vascular disorders
    Hypertension 1/9 (11.1%) 4/57 (7%) 4/57 (7%)
    Hypotension 3/9 (33.3%) 6/57 (10.5%) 5/57 (8.8%)
    Thrombosis/thrombus/embolism 0/9 (0%) 4/57 (7%) 4/57 (7%)

    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 SWOG
    Phone 206-667-4623
    Email
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00617708
    Other Study ID Numbers:
    • NCI-2009-00797
    • NCI-2009-00797
    • CDR0000586427
    • SWOG-S0727
    • S0727
    • S0727
    • U10CA032102
    First Posted:
    Feb 18, 2008
    Last Update Posted:
    Feb 8, 2022
    Last Verified:
    Jan 1, 2022