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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

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ClinicalTrials.gov Identifier: NCT00617708
Recruitment Status : Completed
First Posted : February 18, 2008
Results First Posted : December 5, 2013
Last Update Posted : July 31, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE February 15, 2008
First Posted Date  ICMJE February 18, 2008
Results First Submitted Date  ICMJE October 7, 2013
Results First Posted Date  ICMJE December 5, 2013
Last Update Posted Date July 31, 2014
Study Start Date  ICMJE March 2008
Actual Primary Completion Date September 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 7, 2013)
  • Maximum Tolerated Dose Determination [ Time Frame: 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).
  • Progression-Free Survival [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 15, 2008)
  • Recommended phase II dose of anti-IGF-1R recombinant monoclonal antibody IMC-A12 when given in combination with gemcitabine hydrochloride and erlotinib hydrochloride (Phase I)
  • Progression-free survival (Phase II)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2013)
  • Overall Survival [ Time Frame: 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.
  • Response [ Time Frame: 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.
  • Toxicity [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 15, 2008)
Overall survival (Phase II)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
Detailed Description

PRIMARY OBJECTIVES:

I. To assess the appropriate dose of IMC-A12 (cixutumumab) to use in combination with gemcitabine (gemcitabine hydrochloride) and erlotinib (erlotinib hydrochloride). (Phase I) II. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Stage IV Pancreatic Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: cixutumumab
    • Drug: erlotinib hydrochloride
    • Drug: gemcitabine hydrochloride
  • 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.
    Interventions:
    • Drug: erlotinib hydrochloride
    • Drug: gemcitabine hydrochloride
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 7, 2013)
134
Original Enrollment  ICMJE
 (submitted: February 15, 2008)
118
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date September 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00617708
Other Study ID Numbers  ICMJE NCI-2009-00797
NCI-2009-00797 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000586427
SWOG-S0727
S0727 ( Other Identifier: Southwest Oncology Group )
S0727 ( Other Identifier: CTEP )
U10CA032102 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Philip Philip Southwest Oncology Group
PRS Account National Cancer Institute (NCI)
Verification Date October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP