Sorafenib With or Without Gemcitabine in Treating Patients With Metastatic Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00114244
First received: June 13, 2005
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

This randomized phase II is studying how well giving sorafenib with or without gemcitabine works in treating patients with metastatic pancreatic cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with gemcitabine may kill more tumor cells.


Condition Intervention Phase
Stage IV Pancreatic Cancer
Drug: sorafenib tosylate
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of BAY 43-9006 in Combination With Gemcitabine in Metastatic Pancreatic Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response (OR = CR or PR) as determined by the RECIST criteria [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Response rates will be calculated as the percent of eligible patients in an arm whose best response is a CR or PR, and exact 95% confidence intervals will be calculated for this estimate.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: From first day of treatment to time of death due to any cause, assessed up to 6 months ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier by arm. The probability of progression-free survival at 3 months and overall survival at 6 months, and their Greenwood's standard errors will be summarized by arm.

  • Progression-free survival [ Time Frame: From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 3 months ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier by arm. The probability of progression-free survival at 3 months and overall survival at 6 months, and their Greenwood's standard errors will be summarized by arm.

  • Overall survival [ Time Frame: From first day of treatment to time of death due to any cause, assessed up to 3 months ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier by arm.

  • Time to progression [ Time Frame: From first day of treatment to the first observation of disease progression or death due to disease, assessed up to 3 months ] [ Designated as safety issue: No ]
    For those patients in Arm I who receive gemcitabine/BAY 43-9006 after progression, the times to progression will be compared using a signed rank Wilcoxon test for paired data.

  • Disease control (CR or PR or SD) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Response rates will be calculated as the percent of eligible patients in an arm whose best response is a CR or PR, and exact 95% confidence intervals will be calculated for this estimate.

  • Toxicity, in terms of type, severity, time of onset, time of resolution, and the probable association with the study regimen as measured by CTC version 3.0 [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
    Tables will be constructed to summarize the observed incidence by arm, severity and type of toxicity.


Enrollment: 74
Study Start Date: December 2004
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (sorafenib tosylate)
Patients receive oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II.
Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (sorafenib tosylate, gemcitabine hydrochloride)
Patients receive oral sorafenib as in Arm I and gemcitabine IV over 100 minutes on days 1, 8, and 15.
Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the objective response rate in patients with metastatic pancreatic cancer treated with concurrent gemcitabine and BAY43-9006 and sequential BAY 43-9006 followed by gemcitabine/BAY 43-9006 at progression.

SECONDARY OBJECTIVES:

I. To determine the six month overall survival rate, 3 month progression free survival rate, time to tumor progression and overall survival of patients with metastatic pancreatic cancer treated with concurrent gemcitabine and BAY43-9006 and sequential BAY 43-9006 followed by gemcitabine/BAY 43-9006 at progression.

II. To determine the safety profile of gemcitabine and BAY43-9006 in patients with metastatic pancreatic cancer and compared to those treated with single agent BAY 43-9006.

III. To determine whether mRNA expression levels of genes involved in the gemcitabine pathway (RR, dck, dcd) and genes involved in the Raf pathway (cyclin D, VEGFR2, p21) will predict for time to progression, overall survival, and response, in patients with metastatic pancreatic cancer treated with concurrent gemcitabine and BAY43-9006 and sequential BAY 43-9006 followed by gemcitabine/BAY 43-9006 at progression.

IV. To determine whether genomic polymorphisms of genes (measured in peripheral blood mononuclear cells) involved in the gemcitabine pathway (RR) and genes involved in the ras pathway (VEGFR2, cyclin D, p21) will predict for time to progression, overall survival, tumor response, and toxicity in patients with advanced cancer of the pancreas treated with concurrent gemcitabine and BAY43-9006 and sequential BAY 43-9006 followed by gemcitabine/BAY 43-9006 at progression.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II.

ARM II: Patients receive oral sorafenib as in Arm I and gemcitabine IV over 100 minutes on days 1, 8, and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed metastatic pancreatic carcinoma
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
  • No prior chemotherapy for metastatic disease is allowed; prior adjuvant chemotherapy is allowed provided that patients did not receive gemcitabine and the chemotherapy completed > 6 months prior to initiation of study therapy
  • Available tumor biopsy specimen (paraffin embedded or fresh frozen) that was obtained at the time of diagnosis and/or prior to study entry is required
  • Life expectancy of greater than 3 months
  • ECOG performance status =< 1
  • Leukocytes >= 3,000/μL
  • Absolute neutrophil count >= 1,500/μL
  • Platelets >= 100,000/μL
  • Hemoglobin >= 9 mg/dL
  • Total bilirubin =< 1.5 X institutional upper limit of normal
  • AST(SGOT)/ALT(SGPT) =< 3 X institutional upper limit of normal, unless the liver is involved with tumor, in which the AST (SGOT)/ALT (SGPT) must be =< 5 X institutional upper limit of normal
  • Creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2
  • The effects of BAY 43-9006 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because raf kinase inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Because BAY 43-9006 is at least partially metabolized by the CYP 3A enzyme in the liver, the possible effect that inhibitors of CYP 3A may have on BAY 43-9006 is unknown; therefore, patients taking inhibitors of CYP 3A (such as ketoconazole, itraconazole, and ritonavir) may not be enrolled in this study
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006 or gemcitabine
  • Secondary primary malignancy (except in situ carcinoma of the cervix, in situ cancer of the prostate, in situ cancer of the breast or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 5 years previously with no evidence of recurrence); concurrent or history of another malignancy =< 5 years
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because BAY 43-9006 is a kinase inhibitor agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BAY 43-9006, breastfeeding should be discontinued if the mother is treated with BAY 43-9006
  • Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
  • Patients with evidence of bleeding diathesis
  • Patients receiving therapeutic doses of anticoagulation; prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed
  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: NCT00114244

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Heinz-Josef Lenz Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00114244     History of Changes
Other Study ID Numbers: NCI-2012-02835, NCI-2012-02835, PHII-50, 6576, N01CM62209
Study First Received: June 13, 2005
Last Updated: October 25, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Sorafenib
Niacinamide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on September 16, 2014