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

Vanderbilt University Medical Center

Status and phase

Completed

Phase 2

Conditions

Pancreatic Cancer

Treatments

Drug: Erlotinb

Drug: Sorafenib

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00837876

VU-VICC-GI-0815

P30CA068485 (U.S. NIH Grant/Contract)

VICC GI 0815

Details and patient eligibility

About

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.

Full 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.

Enrollment

37 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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