Clinical trial NCT00810719: Gemcitabine and Erlotinib in Treating Patients With Metastatic or Recurrent Pancreatic Cancer
Official title: Phase II Study of Gemcitabine and Intermittent Erlotinib in Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: recurrent pancreatic cancer
stage IV pancreatic cancer
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Genentech, Inc.
First posted: 2008-12-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: Up to 36 months
Secondary outcomes:
measure: Response Rate
timeFrame: Up to 36 months
measure: Overall Survival
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
Study officials:
affiliation: University of California, Davis
name: Primo N. Lara, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.