Clinical trial NCT00837876: Sorafenib and Erlotinib in Treating Patients With Pancreatic Cancer That Cannot Be Removed by Surgery
Official title: A Phase II Trial of Sorafenib and Erlotinib in Unresectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: recurrent pancreatic cancer
stage III pancreatic cancer
stage IV pancreatic cancer
adenocarcinoma of the pancreas
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-02-06
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Number of Patients With Progression-free Survival
timeFrame: at 8 weeks
Secondary outcomes:
measure: Response Rate
timeFrame: at 4 months
measure: Number of Patients With Progression-free Survival
timeFrame: at 4 months
measure: Number of Patients With Worst Grade Toxicities
timeFrame: every 4 weeks and every 8 weeks in follow-up to resolution of toxicity
Other outcomes:
Locations:
city: Paducah
country: United States
facility: Purchase Cancer Group - Paducah
state: Kentucky
city: Chattanooga
country: United States
facility: Erlanger Cancer Center at Erlanger Hospital - Baroness
state: Tennessee
city: Knoxville
country: United States
facility: Baptist Regional Cancer Center at Baptist Riverside
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center - Cool Springs
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Franklin
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Jordan D. Berlin, MD
role: PRINCIPAL_INVESTIGATOR
References: