Gemcitabine and Imatinib Mesylate as First-Line Therapy in Patients With Locally Adv. or Metastatic Pancreatic Cancer

Phase II Study of Imatinib Mesylate and Gemcitabine for First-line Treatment of Metastatic Pancreatic Cancer

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. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with imatinib mesylate may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gemcitabine together with imatinib mesylate works as first-line therapy in treating patients with locally advanced or metastatic pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: imatinib mesylate

Detailed Description

OBJECTIVES:

Primary

• Evaluate the time to progression in patients with locally advanced or metastatic pancreatic cancer treated with gemcitabine hydrochloride and imatinib mesylate as first-line therapy.

Secondary

• Assess the response rate in patients treated with this regimen.
• Assess the percentage of patients treated with this regimen who survive 1 year or more.
• Assess the toxicity of this regimen in these patients.
• Assess the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter, nonrandomized, open-label, uncontrolled study.

Patients receive gemcitabine hydrochloride IV over 120 minutes on days 3 and 10 and oral imatinib mesylate on days 1-5 and 8-12. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • CentraState Medical Center
    • Hamilton, New Jersey, United States, 08690
      • Cancer Institute of New Jersey At Hamilton
    • Neptune, New Jersey, United States, 07754
      • Jersey Shore Cancer Center at Jersey Shore University Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
    • New Brunswick, New Jersey, United States, 08903
      • Saint Peter's University Hospital
    • New Brunswick, New Jersey, United States, 08901
      • Central Jersey Oncology Group
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed pancreatic adenocarcinoma or poorly differentiated carcinoma (originating in the pancreas)

  • Locally advanced or metastatic disease
• Not eligible for curative resection

• Must have measurable or evaluable disease as defined by RECIST criteria

  • No CA19-9 elevation as only evidence of disease
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 125,000/mm³
• Bilirubin < 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Alkaline phosphatase < 3 times ULN
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective nonhormonal contraception
• No coexisting medical condition that would preclude study compliance
• No inability to ingest tablets
• No active illness (e.g., active or uncontrolled infection, uncontrolled cardiac disease) that would preclude study participation
• No chronic uncontrolled diarrhea and/or daily emesis
• No other cancer within the past 5 years except for surgically removed noninvasive nonmelanoma skin cancer or in situ cervical cancer

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy for metastatic disease
• No prior gemcitabine
• No prior imatinib mesylate
• Prior surgical resection and adjuvant fluorouracil chemotherapy allowed provided there was an interval of > 6 months between the last dose of adjuvant chemotherapy and recurrence of pancreatic cancer
• Prior fluorouracil as a radiosensitizing agent allowed

• At least 4 weeks since prior radiotherapy and recovered

  • Must have evidence of disease outside the radiation fields OR radiologically confirmed disease progression within the radiation fields after completion of radiotherapy

• No concurrent therapeutic warfarin

  • Prophylactic warfarin ≤ 1 mg daily allowed for prophylaxis of central venous catheter thrombosis
  • Low molecular weight heparin or heparin allowed for anticoagulation
• No concurrent chronic systemic corticosteroids
• No other concurrent agents or therapies, including chemotherapy, immunotherapy, hormonal cancer therapy, radiotherapy, or cancer surgery
• No other concurrent experimental medications
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemcitabine and Imatinib	Drug: gemcitabine hydrochloride; Drug: imatinib mesylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival in months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		5 years
Response Rate	Response rate as defined by a best response of "Stable Disease or better."	5 years
1-year Survival Rate	Percentage of subjects who survive up to 1 year	5 years

Collaborators and Investigators

• Sponsor: University of Medicine and Dentistry of New Jersey
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Elizabeth A. Poplin, MD, Rutgers Cancer Institute of New Jersey

Publications and helpful links

General Publications

• Moss RA, Moore D, Mulcahy MF, Nahum K, Saraiya B, Eddy S, Kleber M, Poplin EA. A Multi-institutional Phase 2 Study of Imatinib Mesylate and Gemcitabine for First-Line Treatment of Advanced Pancreatic Cancer. Gastrointest Cancer Res. 2012 May;5(3):77-83.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 11, 2005
• First Posted (Estimated): September 12, 2005

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: recurrent pancreatic cancer; adenocarcinoma of the pancreas; stage IV pancreatic cancer; stage III pancreatic cancer; stage II pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate; Gemcitabine
• Other Study ID Numbers: CDR0000539409; P30CA072720 (U.S. NIH Grant/Contract); CINJ-070501 (Other Identifier: CINJ); CINJ-5324 (Other Identifier: CINJ); CINJ-NJ1205 (Other Identifier: CINJ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO