Sorafenib With Or Without Gemcitabine In Treating Patients With Metastatic Pancreatic Cancer

Study Overview

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

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.

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.

Stage IV Pancreatic Cancer

DRUG: sorafenib tosylate
DRUG: gemcitabine hydrochloride
OTHER: laboratory biomarker analysis

NCI-2012-02835
NCI-2012-02835 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
PHII-50 (OTHER Identifier) (OTHER: City of Hope)
6576 (OTHER Identifier) (OTHER: CTEP)
N01CM62209 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2005-06-13	Results First Submitted 2015-01-06	Last Update Submitted that met QC Criteria 2015-01-06
First Submitted that Met QC Criteria 2005-06-13	Results First Submitted that Met QC Criteria 2015-01-06	Last Update Posted (ESTIMATED) 2015-01-14
First Posted (ESTIMATED) 2005-06-14	Results First Posted 2015-01-14	Last Verified 2013-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Crossover

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm I (sorafenib tosylate) Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II.	DRUG: sorafenib tosylate Given PO OTHER: laboratory biomarker analysis Correlative studies
EXPERIMENTAL: Arm II (sorafenib tosylate, gemcitabine hydrochloride) Patients receive 400 mg oral sorafenib as in Arm I and 1000 mg/m2 gemcitabine IV over 100 minutes on days 1, 8, and 15.	DRUG: sorafenib tosylate Given PO DRUG: gemcitabine hydrochloride Given IV OTHER: laboratory biomarker analysis Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Arm I (sorafenib tosylate)

Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II.

DRUG: sorafenib tosylate

Given PO

OTHER: laboratory biomarker analysis

Correlative studies

EXPERIMENTAL: Arm II (sorafenib tosylate, gemcitabine hydrochloride)

Patients receive 400 mg oral sorafenib as in Arm I and 1000 mg/m2 gemcitabine IV over 100 minutes on days 1, 8, and 15.

DRUG: sorafenib tosylate

Given PO

DRUG: gemcitabine hydrochloride

Given IV

OTHER: laboratory biomarker analysis

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
Objective Response (OR = CR or PR) as Determined by the RECIST Criteria	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan, MRI, X-ray: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	Every 6 weeks.

Secondary Outcome Measures	Measure Description	Time Frame
Overall Survival	Estimated using the product-limit method of Kaplan and Meier by arm.	From first day of treatment to time of death due to any cause, assessed up to 6 months
Progression-free Survival	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.	From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 3 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Heinz-Josef Lenz, City of Hope Medical Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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