Gemcitabine and Erlotinib With or Without Monoclonal Antibody Therapy in Treating Patients With Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery - Full Text View

Sponsor:	Southwest Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00617708

Purpose

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib 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 and gemcitabine together with monoclonal antibody therapy may kill more tumor cells.

PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of monoclonal antibody therapy when given together with gemcitabine and erlotinib and to see how well they work compared with giving gemcitabine and erlotinib alone as first-line therapy in treating patients with metastatic pancreatic cancer that cannot be removed by surgery.

Condition	Intervention	Phase
Pancreatic Cancer	Biological: cixutumumab Drug: erlotinib hydrochloride Drug: gemcitabine hydrochloride	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized
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:

MedlinePlus related topics: Cancer Pancreatic Cancer Surgery

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

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

Primary Outcome Measures:

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) [ Designated as safety issue: Yes ]
Progression-free survival (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival (Phase II) [ Designated as safety issue: No ]

Estimated Enrollment:	118
Study Start Date:	March 2008
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I (phase II): Experimental Patients receive oral erlotinib hydrochloride once daily on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and IMC-A12 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 Drug: erlotinib hydrochloride Given orally Drug: gemcitabine hydrochloride Given IV
Arm II (phase II): Active Comparator 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 orally Drug: gemcitabine hydrochloride Given IV

Detailed Description:

OBJECTIVES:

To assess the appropriate dose of anti-IGF-1R recombinant monoclonal antibody IMC-A12 (IMC-A12) in combination with gemcitabine hydrochloride and erlotinib hydrochloride as first-line therapy in patients with unresectable, metastatic pancreatic cancer. (Phase I)
To assess progression-free survival in patients treated with gemcitabine hydrochloride and erlotinib hydrochloride with vs without IMC-A12. (Phase II)
To assess overall survival in patients treated with these regimens. (Phase II)
To assess the total response probability (confirmed and unconfirmed, complete and partial responses) in patients with measurable disease treated with these regimens. (Phase II)
To assess the qualitative and quantitative toxicities in patients treated with these regimens. (Phase II)
To explore whether expression levels of genes involved in the EGFR, IGFR, and gemcitabine hydrochloride pathways (VEGF, IL-8, cycline D, IGFR, IGFII, cda, cdk, RRM1, and RRM2) in the tumor tissue of patients treated with gemcitabine hydrochloride, erlotinib hydrochloride, and IMC-A12 are associated with clinical outcome. (Phase II)
To explore whether germline polymorphisms (DNA) of genes involved in the EGFR, IGFR, and gemcitabine hydrochloride pathways (VEGF, IL-8, cycline D, IGFR, RRM1, RRM2, cda, and cdk) are associated with toxicity and clinical outcome. (Phase II)
To explore whether mutations in the RAS and P13K oncogenes will be associated with clinical outcome. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of anti-IGF-1R recombinant monoclonal antibody IMC-A12 (IMC-A12) 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 IMC-A12. Once the RPTD is determined, patients are enrolled into the phase II portion of the study.

Phase I (Limited institutions): Patients receive oral erlotinib hydrochloride once daily on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and IMC-A12 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 IMC-A12 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

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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

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

Show 122 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Robert P. Whitehead, MD	University of Texas
Investigator:	Chris H. Takimoto, MD, PhD, FACP	South Texas Accelerated Research Therapeutics

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Southwest Oncology Group - Group Chair's Office ( Laurence H. Baker )
Study ID Numbers:	CDR0000586427, SWOG-S0727
Study First Received:	February 15, 2008
Last Updated:	February 4, 2010
ClinicalTrials.gov Identifier:	NCT00617708 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IV pancreatic cancer

Additional relevant MeSH terms:

Erlotinib
Antimetabolites
Anti-Infective Agents
Digestive System Neoplasms
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Endocrine System Diseases
Enzyme Inhibitors

Protein Kinase Inhibitors
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Digestive System Diseases
Radiation-Sensitizing Agents
Therapeutic Uses
Pancreatic Diseases
Gemcitabine
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010