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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Trial of Sorafenib and Erlotinib in Unresectable Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Sorafenib
* Drug: Erlotinb


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Sorafenib + Erlotinib | Drug: Sorafenib<br>* 400 mg taken by mouth 1 time per day.<br>Drug: Erlotinb<br>* 150 mg taken by mouth 1 time per day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent pancreatic cancer, stage III pancreatic cancer, stage IV pancreatic cancer, adenocarcinoma of the pancreas