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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00617708
First received: February 15, 2008
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Stage IV Pancreatic Cancer
Biological: cixutumumab
Drug: erlotinib hydrochloride
Drug: gemcitabine hydrochloride
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum Tolerated Dose Determination [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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:
  • Overall Survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 134
Study Start Date: March 2008
Study Completion Date: September 2013
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00617708

  Show 146 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Philip Philip Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00617708     History of Changes
Other Study ID Numbers: NCI-2009-00797, NCI-2009-00797, CDR0000586427, SWOG-S0727, S0727, S0727, U10CA032102
Study First Received: February 15, 2008
Results First Received: October 7, 2013
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antibodies
Antibodies, Monoclonal
Gemcitabine
Erlotinib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014