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A Randomized Phase II Study of BAY 43-9006 in Combination With Gemcitabine in Metastatic Pancreatic Carcinoma


Phase 2
18 Years
N/A
Not Enrolling
Both
Stage IV Pancreatic Cancer

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Trial Information

A Randomized Phase II Study of BAY 43-9006 in Combination With Gemcitabine in Metastatic Pancreatic Carcinoma


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response (OR = CR or PR) as determined by the RECIST criteria

Outcome Description:

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.

Outcome Time Frame:

Up to 6 years

Safety Issue:

No

Principal Investigator

Heinz-Josef Lenz

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02835

NCT ID:

NCT00114244

Start Date:

December 2004

Completion Date:

Related Keywords:

  • Stage IV Pancreatic Cancer
  • Pancreatic Neoplasms

Name

Location

City of HopeDuarte, California  91010