Gemcitabine and Erlotinib in Treating Patients With Metastatic or Recurrent Pancreatic Cancer

Phase II Study of Gemcitabine and Intermittent Erlotinib in Advanced 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. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with erlotinib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gemcitabine together with erlotinib works in treating patients with metastatic or recurrent pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Erlotinib; Drug: gemcitabine

Detailed Description

OUTLINE: This is a multicenter study.

Patients receive gemcitabine hydrochloride IV on days 1, 8, and 15 and oral erlotinib hydrochloride on days 2-5, 9-12, and 16-26. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Archived tumor tissue samples are analyzed for the expression of EGFR, HER3, HER2, downstream signaling molecules, and other molecular markers by immunohistochemistry and RT-PCR. The presence of aberrant gene copy numbers (amplification and polysomy) for EGFR, HER3, and HER2 are determined by FISH. Blood samples are collected at baseline and periodically during study for polymorphism analysis and correlative molecular analysis of surrogate endpoint biomarkers.

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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically or cytologically confirmed locally advanced, metastatic or recurrent pancreatic carcinoma
• Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
• No prior chemotherapy for metastatic or recurrent disease is allowed. Prior adjuvant chemotherapy is allowed provided that patients did not receive gemcitabine and the chemotherapy was completed > six months prior to initiation of study therapy. Prior erlotinib therapy is not allowed
• Available tumor specimen that was obtained at the time of diagnosis and/or prior to study entry is highly encouraged
• Age ≥ 18 years
• Life expectancy greater than 3 months
• Zubrod performance status ≤ 2
• Patients must have normal organ and marrow function as defined below:
• leukocytes ≥ 3,000/μL
• absolute neutrophil count ≥ 1,500/ μL
• platelets ≥ 100,000/ μL
• total bilirubin ≤ 1.5 X institutional upper limit of normal
• AST(SGOT)/ALT(SGPT) ≤ 3 X institutional upper limit of normal, unless the liver is involved with tumor, in which case the AST/ALT must be ≤ 5 X institutional upper limit of normal
• creatinine clearance ≥ 50 mL/min/1.73 m2, as measured by 24hour collection OR
• creatinine ≤ 1.5 X institutional upper limit of normal
• The effects of erlotinib and gemcitabine on the developing human fetus at the recommended therapeutic doses are unknown. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients may not be receiving any other investigational agents.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib or gemcitabine.
• Secondary primary malignancy. Concurrent or history of another malignancy < 5 years.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because erlotinib and gemcitabine have the potential for teratogenic or abortifacient effects. Breastfeeding should be discontinued if the mother is treated with study drugs.
• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy.

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 Erlotinib; The dose for gemcitabine is 1,000 mg/m2 administered over 30 minutes as an intravenous infusion. The doses are administered weekly for 3 weeks (Days 1, 8 and 15) followed by one week of rest during which gemcitabine is not given. This 4 week period (28 days) constitutes a cycle.Erlotinib will be dosed at 150mg orally (tablets) on days 2-5, 9-12, and 16-26 of a 28 day cycle.

Drug: Erlotinib; Erlotinib will be administered at 150 mg once daily by mouth on the following schedule: days 2-5, 9-12,16-26.; Other Names: Tarceva; Drug: gemcitabine; The dose for gemcitabine is 1,000 mg/m2 administered over 30 minutes as an intravenous infusion. The doses are administered weekly for 3 weeks (Days 1, 8 and 15) followed by one week of rest during which gemcitabine is not given. This 4 week period (28 days) constitutes a cycle.; Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Defined as the time from first day of treatment to the first observation of disease progression or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up. 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.	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to 36 months
Overall Survival	Overall survival will be followed for survival every three months until documented progression, death or study termination. If a participant is still alive, survival time is censored at the time of last follow-up.	Up to 36 months

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: National Cancer Institute (NCI); Genentech, Inc.
• Investigators: Principal Investigator: Primo N. Lara, MD, University of California, Davis

Publications and helpful links

General Publications

• Semrad T, Barzi A, Lenz HJ, Hutchins IM, Kim EJ, Gong IY, Tanaka M, Beckett L, Holland W, Burich RA, Snyder-Solis L, Mack P, Lara PN Jr. Pharmacodynamic separation of gemcitabine and erlotinib in locally advanced or metastatic pancreatic cancer: therapeutic and biomarker results. Int J Clin Oncol. 2015 Jun;20(3):518-24. doi: 10.1007/s10147-014-0730-2. Epub 2014 Aug 5.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: December 17, 2008
• First Submitted That Met QC Criteria: December 17, 2008
• First Posted (Estimate): December 18, 2008

Study Record Updates

• Last Update Posted (Actual): January 10, 2018
• Last Update Submitted That Met QC Criteria: January 5, 2018
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: recurrent pancreatic cancer; stage IV 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gemcitabine; Erlotinib Hydrochloride
• Other Study ID Numbers: UCDCC#211; P30CA093373 (U.S. NIH Grant/Contract); 232494 (Other Identifier: UC Davis); OSI 4132s (Other Identifier: Genentech)