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

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

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Sorafenib; Drug: Erlotinb

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Paducah, Kentucky, United States, 42002
      • Purchase Cancer Group - Paducah
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Cancer Center at Erlanger Hospital - Baroness
    • Knoxville, Tennessee, United States, 37901
      • Baptist Regional Cancer Center at Baptist Riverside
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37064
      • Vanderbilt-Ingram Cancer Center - Cool Springs
    • Nashville, Tennessee, United States, 37064
      • Vanderbilt-Ingram Cancer Center at Franklin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jordan D. Berlin, MD, Vanderbilt-Ingram Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: February 5, 2009
• First Submitted That Met QC Criteria: February 5, 2009
• First Posted (Estimate): February 6, 2009

Study Record Updates

• Last Update Posted (Estimate): June 25, 2014
• Last Update Submitted That Met QC Criteria: June 13, 2014
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: recurrent pancreatic cancer; adenocarcinoma of the pancreas; stage IV pancreatic cancer; stage III pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: VICC GI 0815; P30CA068485 (U.S. NIH Grant/Contract); VU-VICC-GI-0815