Sorafenib and Gemcitabine in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

A Phase II Study of BAY 43-9006/Gemcitabine for Advanced Pancreatic Cancer

Sorafenib may stop the growth of tumor cells by stopping blood flow to the tumor and by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving sorafenib with gemcitabine may kill more tumor cells. This phase II trial is studying how well giving sorafenib together with gemcitabine works in treating patients with locally advanced or metastatic pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; Stage II Pancreatic Cancer
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: sorafenib tosylate

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the objective response rate in patients with locally advanced or metastatic adenocarcinoma of the pancreas treated with sorafenib and gemcitabine.

II. Determine the toxicity experienced by patients with advanced pancreatic cancer who are treated with sorafenib plus gemcitabine.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-28 and gemcitabine IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 12-35 patients will be accrued for this study within 7 months.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

  • Locally advanced or metastatic disease

    • Locally advanced disease must extend outside the boundaries of a standard radiotherapy port
• Not amenable to curative surgery or radiotherapy

• Measurable disease

  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
  • Pleural effusion and ascites are not considered measurable lesions
  • Outside prior radiotherapy port
• No known brain metastases
• Performance status - ECOG 0-1
• Performance status - Karnofsky 70-100%
• More than 3 months
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No evidence of bleeding diathesis
• Bilirubin normal
• AST and/or ALT ≤ 2.5 times upper limit of normal
• Creatinine normal
• Creatinine clearance ≥ 60 mL/min
• No uncontrolled hypertension
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active or ongoing infection
• No other active malignancy
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to sorafenib or other study agents
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No prior antiangiogenic agents
• No prior cytotoxic chemotherapy for metastatic disease
• At least 4 weeks since prior adjuvant chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior gemcitabine
• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• No prior investigational drugs
• No prior sorafenib
• No prior MAPK signaling agents

• Concurrent warfarin anticoagulation allowed provided the following criteria are met:

  • Therapeutic on a stable warfarin dose
  • INR ≤ 3
  • Undergo weekly INR testing
  • No active bleeding or pathological condition that carries a high risk of bleeding
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (sorafenib tosylate and gemcitabine hydrochloride); Patients receive oral sorafenib twice daily on days 1-28 and gemcitabine IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: gemcitabine hydrochloride; Given IV; Other Names: Gemzar; gemcitabine; dFdC; difluorodeoxycytidine hydrochloride; Drug: sorafenib tosylate; Given orally; Other Names: BAY 43-9006; BAY 43-9006 Tosylate Salt; BAY 54-9085; Nexavar; SFN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate as measured by RECIST criteria	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Kaplan-Meier curves will be constructed.	From start of treatment to progression or death, assessed up to 6 months
Survival	Specific attention will be given to the six-month survival rate, for which 90% confidence intervals will be generated.	At 6 months
Overall survival	Kaplan-Meier curves will be constructed	Up to 6 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): September 1, 2005

Study Registration Dates

• First Submitted: November 9, 2004
• First Submitted That Met QC Criteria: November 8, 2004
• First Posted (Estimate): November 9, 2004

Study Record Updates

• Last Update Posted (Estimate): July 2, 2013
• Last Update Submitted That Met QC Criteria: July 1, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gemcitabine; Sorafenib
• Other Study ID Numbers: NCI-2012-02629; N01CM62201 (U.S. NIH Grant/Contract); U01CA099118 (U.S. NIH Grant/Contract); 13169B; CDR0000391850; NCI-6567; UCCRC-13169B