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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jordan Berlin, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00837876
First received: February 5, 2009
Last updated: June 13, 2014
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Drug: Sorafenib
Drug: Erlotinb
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Sorafenib and Erlotinib in Unresectable Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Number of Patients With Progression-free Survival [ Time Frame: at 8 weeks ] [ Designated as safety issue: No ]
    Number of patients with progression-free survival at 8 weeks


Secondary Outcome Measures:
  • Response Rate [ Time Frame: at 4 months ] [ Designated as safety issue: No ]
    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

  • Number of Patients With Progression-free Survival [ Time Frame: at 4 months ] [ Designated as safety issue: No ]
    Participants with progression-free survival at 4 months.

  • Number of Patients With Worst Grade Toxicities [ Time Frame: every 4 weeks and every 8 weeks in follow-up to resolution of toxicity ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 37
Study Start Date: October 2008
Study Completion Date: November 2012
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00837876

Locations
United States, Kentucky
Purchase Cancer Group - Paducah
Paducah, Kentucky, United States, 42002
United States, Tennessee
Erlanger Cancer Center at Erlanger Hospital - Baroness
Chattanooga, Tennessee, United States, 37403
Baptist Regional Cancer Center at Baptist Riverside
Knoxville, Tennessee, United States, 37901
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Principal Investigator: Jordan D. Berlin, MD Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

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, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00837876     History of Changes
Other Study ID Numbers: VICC GI 0815, P30CA068485, VU-VICC-GI-0815
Study First Received: February 5, 2009
Results First Received: April 2, 2012
Last Updated: June 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:
recurrent pancreatic cancer
stage III pancreatic cancer
stage IV pancreatic cancer
adenocarcinoma of the pancreas

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Erlotinib
Sorafenib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 31, 2014