Sorafenib Tosylate With or Without Recombinant Interferon Alfa-2b in Treating Patients With Metastatic Kidney Cancer

Clear Cell Renal Cell Carcinoma Clinical Trial

Official title:

A Phase II Clinical Trial to Evaluate the Efficacy of BAY 43-9006 With or Without Low Dose Interferon in Metastatic Renal Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00126594
• Other study ID #: NCI-2012-02910
• Secondary ID: NCI-2012-02910CD
• Status: Completed
• Phase: Phase 2
• First received: August 2, 2005
• Last updated: December 22, 2014
• Start date: June 2005
• Est. completion date: August 2013

Study information

• Verified date: December 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial is studying sorafenib and interferon alfa-2b to see how well they work compared to sorafenib alone in treating patients with metastatic kidney cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Interferon alfa-2b may interfere with the growth of tumor cells. Sorafenib and interferon alfa-2b may also block blood flow to the tumor. Giving sorafenib together with interferon alfa-2b may kill more tumor cells.

Description:

PRIMARY OBJECTIVES:

I. Efficacy of Bay 43-9006 with or without low dose interferon by evaluating response rate in MRCC.

II. Toxicities of Bay 43-9006 with or without low dose interferon in MRCC.

SECONDARY OBJECTIVES:

I. Progression free survival. II. Duration of response. III. Overall Survival.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral sorafenib twice daily on days 1-28.

Arm II: Patients receive sorafenib as in arm I and low-dose interferon alfa-2b subcutaneously twice daily on days 1-28.

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

Tissue samples are analyzed for single nucleotide polymorphisms (SNP) patterns via genotyping.

After completion of study treatment, patients are followed every 3 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with histologically or cytologically confirmed metastatic clear cell RCC

• Patients must have measurable disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures >= 20 mm with conventional techniques or >= 10 mm with spiral CT scan

• ECOG performance status =< 1

• Absolute neutrophil count >= 1,500/µL

• Platelets >= 100,000/µL

• Hgb > 9.0 g/dL (may be transfused or receive epoetin alfa [e.g., Epogen®] to maintain or exceed this level)

• Total bilirubin =< 2.0 mg/dl

• Albumin > 3.0 g/dL

• Serum creatinine =< 2.0 mg/dl

• AST(SGOT) and/or ALT (SGPT) =< 2.5 X institutional upper limit of normal for subjects without evidence of liver metastases

• AST(SGOT) and/or ALT (SGPT) =< 5 X institutional upper limit of normal for subjects with documented liver metastases

• Female patients of childbearing potential must have a normal plasma beta human chorionic gonadotropin (ßHCG) within 24 hours prior to enrolling in the study due to the possible teratogenic effect; however, patients will be eligible if their ßHCG elevation is consistent with malignancy rather than pregnancy

• Patients of child fathering or childbearing potential must agree to practice a form of medically acceptable birth control while on study

• Patients must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution; patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy; the only approved consent is attached to this protocol

• Patients must have ability to comply with study and/or follow-up procedures

• Patients must be able to swallow pills

Exclusion Criteria:

• No prior malignancy is allowed, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 5 years

• Patients must not have received any systemic anticancer therapy for renal cell carcinoma; patients must not have received any radiotherapy for renal cell carcinoma within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Patients must not be scheduled to receive another experimental drug while on this study; patients are permitted to be on concomitant bisphosphonates

• Patients must not have a primary brain tumor, any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or history of stroke

• Patients must not have active acute infections that could be worsened by anticancer therapy or interfere with this study

• Patients must not have clinically significant cardiovascular disease, myocardial infarction within the past year (unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac dysrhythmia refractory to medical management, or peripheral vascular disease (Grade II or greater)

• Patients must not have uncontrolled hypertension

• Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications

• 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 must not have a clinical history of coagulopathy, bleeding diathesis or thrombosis; patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (ie low dose warfarin) of venous access devices is allowed provided that INR >= 1.5 is due to warfarin therapy; other patients with an INR >= 1.5 are excluded

• Patients must not have a history of severe depression

• Concomitant treatment with rifampin, St. John's wort, and the cytochrome p450 enzyme-inducin antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital)

Study Design

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma
• Recurrent Renal Cell Carcinoma
• Stage IV Renal Cell Cancer

Intervention

Drug:
• Sorafenib Tosylate
Given orally

Biological:
• Recombinant Interferon Alfa-2b
Given SC

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (CR+PR) evaluated using RECIST criteria	95% exact binomial confidence interval will be computed. Compared between arms using a chi-square test or Fisher's exact test, as appropriate.	Up to 3 months	No
Secondary	Adverse events graded using the NCI CTCAE version 4.0	Tabulated by treatment arm and toxicity grade.	Up to 3 months	Yes
Secondary	Progression-free survival	Analyzed using Kaplan-Meier life table methods and Cox proportional hazards regression modeling.	From the start of protocol therapy to death or disease progression, assessed up to 3 months	No
Secondary	Overall survival	Analyzed using Kaplan-Meier life table methods and Cox proportional hazards regression modeling.	From the start of protocol therapy to death or date of last follow-up, assessed up to 3 months	No
Secondary	Duration of response	Analyzed using Kaplan-Meier life table methods and Cox proportional hazards regression modeling.	From the date response is confirmed to the date of disease progression, assessed up to 3 months	No