Sorafenib And Erlotinib In Treating Patients With Pancreatic Cancer That Cannot Be Removed By Surgery

Study Overview

Sorafenib and Erlotinib in Treating Patients With Pancreatic Cancer That Cannot Be Removed by Surgery

RATIONALE: Sorafenib and erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with erlotinib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving sorafenib together with erlotinib works in treating patients with pancreatic cancer that cannot be removed by surgery.

OBJECTIVES: Primary * To determine the efficacy of sorafenib tosylate in combination with erlotinib hydrochloride in patients with unresectable pancreatic cancer. Secondary * To determine the response rate in patients treated with this regimen. * To determine the progression-free survival of patients treated with this regimen at 4 months. * To evaluate the safety profile of this regimen in these patients. * To evaluate the change in serum Ca 19-9 levels at baseline and at 8-week intervals. * To evaluate the plasma proteomic profile at baseline and at 8 weeks to correlate with clinical parameters in order to identify potential prognostic or predictive markers. * To analyze single-nucleotide polymorphisms on DNA obtained from pretreatment blood samples to evaluate toxicity and response to erlotinib hydrochloride. OUTLINE: Patients receive oral sorafenib tosylate once or twice daily and oral erlotinib hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Serum samples are collected at baseline and at 8-week intervals to measure Ca 19-9 levels, and plasma and buffy coat samples are collected at baseline and at week 8 for proteomic assessment and genotyping of single-nucleotide polymorphisms associated with response and toxicity to erlotinib hydrochloride. After completion of study treatment, patients are followed up every 3 months.

Pancreatic Cancer

DRUG: Sorafenib
DRUG: Erlotinb

VICC GI 0815
P30CA068485 (U.S. NIH Grant/Contract)
VU-VICC-GI-0815

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2009-02-05	Results First Submitted 2012-04-02	Last Update Submitted that met QC Criteria 2014-06-13
First Submitted that Met QC Criteria 2009-02-05	Results First Submitted that Met QC Criteria 2012-08-23	Last Update Posted (ESTIMATED) 2014-06-25
First Posted (ESTIMATED) 2009-02-06	Results First Posted 2012-09-28	Last Verified 2013-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment Sorafenib + Erlotinib	DRUG: Sorafenib 400 mg taken by mouth 1 time per day. DRUG: Erlotinb 150 mg taken by mouth 1 time per day.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment

Sorafenib + Erlotinib

DRUG: Sorafenib

400 mg taken by mouth 1 time per day.

DRUG: Erlotinb

150 mg taken by mouth 1 time per day.

Primary Outcome Measures	Measure Description	Time Frame
Number of Patients With Progression-free Survival	Number of patients with progression-free survival at 8 weeks	at 8 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Response Rate	Per RECIST criteria v. 1.0: measurable lesions: CR disappearance of target lesions, PR > 30% decrease in the sum of the longest diameter (LD) of target lesions, PD > 20% increase in the sum of the LD of target lesions or appearance of new lesions, SD neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions	at 4 months
Number of Patients With Progression-free Survival	Participants with progression-free survival at 4 months.	at 4 months
Number of Patients With Worst Grade Toxicities	Number of patients with worst-grade toxicity at each of five grades (grade 1 to 5, with 5 most severe) following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death.	every 4 weeks and every 8 weeks in follow-up to resolution of toxicity

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Microscopically confirmed diagnosis of pancreatic adenocarcinoma

Unresectable disease
No neuroendocrine tumors or cystadenocarcinoma
Measurable or evaluable disease by RECIST criteria
No known brain metastases

Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastases

ECOG performance status 0-2
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)
Creatinine ≤ 1.5 times ULN
INR < 1.5 or PT/PTT normal unless patients are receiving anticoagulation treatments
Negative pregnancy test
Not pregnant or nursing
Fertile patients must use effective barrier contraception before, during, and for at least 6 months after completion of study treatment
Able to swallow whole pills
No patients who currently smoke
No cardiac disease, including any of the following:

NYHA class III-IV congestive heart failure
Unstable angina (anginal symptoms at rest)
New-onset angina (began within the past 3 months)
Myocardial infarction within the past 6 months
Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
No uncontrolled hypertension defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg despite optimal medical management
No arterial thrombotic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months
No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 in the past 4 weeks
No other hemorrhage/bleeding event ≥ CTCAE grade 3 in the past 4 weeks
No significant traumatic injury in the past 4 weeks
No known untreated malabsorption problem (e.g., ulcerative colitis, Crohn's disease)
No known HIV positivity or chronic hepatitis B or C
No known or suspected allergy to sorafenib tosylate or erlotinib hydrochloride
No active clinically serious infection > CTCAE grade 2
No serious non-healing wound, ulcer, or bone fracture
No evidence or history of bleeding diathesis or coagulopathy (except for cancer-related blood clots)
No dermatitis ≥ CTCAE grade 2 at baseline
No patients who currently smoke

No prior treatment with antiangiogenics (e.g., bevacizumab, thalidomide, marimastat, interferon alfa, vatalanib, vandetanib, ZD6126, sorafenib, semaxanib, sunitinib, axitinib)
No more than one line of prior therapy for metastatic disease
More than 4 weeks since prior major surgery or open biopsy
No concurrent strong CYP34A inhibitors or inducers
Concurrent warfarin or heparin allowed with the approval of the principal investigator

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Jordan D. Berlin, MD, Vanderbilt-Ingram Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

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Clinical Trial Record