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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00837876
• Other study ID #: VICC GI 0815
• Secondary ID: P30CA068485VU-VI
• Status: Completed
• Phase: Phase 2
• First received: February 5, 2009
• Last updated: June 13, 2014
• Start date: October 2008
• Est. completion date: November 2012

Study information

• Verified date: July 2013
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: November 2012
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Sorafenib
400 mg taken by mouth 1 time per day.
• Erlotinb
150 mg taken by mouth 1 time per day.

Locations

Country	Name	City	State
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	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center - Cool Springs	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center at Franklin	Nashville	Tennessee
United States	Purchase Cancer Group - Paducah	Paducah	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Progression-free Survival	Number of patients with progression-free survival at 8 weeks	at 8 weeks	No
Secondary	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	No
Secondary	Number of Patients With Progression-free Survival	Participants with progression-free survival at 4 months.	at 4 months	No
Secondary	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	Yes