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

NCT ID: NCT00837876

Last Updated: 2014-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2012-11-30

Brief Summary

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.

Detailed Description

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Sorafenib + Erlotinib

Group Type: EXPERIMENTAL

Sorafenib

Intervention Type: DRUG

400 mg taken by mouth 1 time per day.

Erlotinb

Intervention Type: DRUG

150 mg taken by mouth 1 time per day.

Interventions

Sorafenib

400 mg taken by mouth 1 time per day.

Intervention Type: DRUG

Erlotinb

150 mg taken by mouth 1 time per day.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Jordan Berlin, MD

Professor of Medicine; Clinical Director, GI Oncology Program; Director, Phase I Program; Medical Director, Clinical Trials Shared Resources; Medical Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jordan D. Berlin, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center

Locations

Purchase Cancer Group - Paducah

Paducah, Kentucky, United States

Erlanger Cancer Center at Erlanger Hospital - Baroness

Chattanooga, Tennessee, United States

Baptist Regional Cancer Center at Baptist Riverside

Knoxville, Tennessee, United States

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center at Franklin

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

P30CA068485

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VU-VICC-GI-0815

Identifier Type: -

Identifier Source: secondary_id

VICC GI 0815

Identifier Type: -

Identifier Source: org_study_id