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

NCT00126594 | Completed Phase 2 Results

• 6 other identifiers: NCI-2012-02910CDR00004377962004-05266629N01CM62202P30CA016672
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Renal Cell Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST)

  ORR defined as participants with Complete Response (CR) and Partial Response (PR) as defined by RECIST criteria: Complete Response (CR): Disappearance all target lesions. Partial Response (PR): \>30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD. Progressive Disease (PD): \>20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started. Radiologic testing for progressive disease repeated every 8 weeks.

  Tumor restaging performed at 8 weeks following baseline, responding or stable participants restaged at 8 week intervals, up to 12 months.

Secondary Outcomes (4)

• Selected Grade 3-4 Adverse Events Using NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

  Up to 12 months of treatment

• Progression-free Survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

• Median Overall Survival (OS)

  From the start of protocol therapy to death or date of last follow-up, up to 36 months

• Duration of Response for Participants With Stable Disease (N=37) Following Treatment

  From the date response is confirmed to the date of disease progression, up to 12 months

Study Arms (2)

Sorafenib Tosylate

EXPERIMENTAL

Arm I: Oral Sorafenib 400 mg twice daily on days 1-28.

Drug: Sorafenib Tosylate; Other: Laboratory Biomarker Analysis

Sorafenib Tosylate, Recombinant interferon alfa-2b

EXPERIMENTAL

Arm II: Sorafenib as in Arm I and low-dose Interferon alfa-2b 0.5 million units subcutaneously twice daily on days 1-28.

Drug: Sorafenib Tosylate; Biological: Recombinant Interferon Alfa-2b; Other: Laboratory Biomarker Analysis

Interventions

Sorafenib Tosylate DRUG

Given orally 400 mg orally (PO) every 12 hours

Also known as: BAY 54-9085, Nexavar, SFN, BAY 43-9006

Sorafenib Tosylate; Sorafenib Tosylate, Recombinant interferon alfa-2b

Recombinant Interferon Alfa-2b BIOLOGICAL

Given subcutaneously (SC) 0.5 million with +/- 5 % variance (0.475 MU - 0.525 MU); Dose level 0: 0.5 X 10\^6 international units twice daily

Also known as: Alfatronol, Glucoferon, Heberon Alfa, Sch 30500, Urifron, IFN

Sorafenib Tosylate, Recombinant interferon alfa-2b

Laboratory Biomarker Analysis OTHER

Correlative studies

Sorafenib Tosylate; Sorafenib Tosylate, Recombinant interferon alfa-2b

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (βHCG) within 24 hours prior to enrolling in the study due to the possible teratogenic effect; however, patients will be eligible if their βHCG 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

  PMID: 37146227 DERIVED

• Gatto F, Bratulic S, Jonasch E, Limeta A, Maccari F, Galeotti F, Volpi N, Lundstam S, Nielsen J, Stierner U. Plasma and Urine Free Glycosaminoglycans as Monitoring and Predictive Biomarkers in Metastatic Renal Cell Carcinoma: A Prospective Cohort Study. JCO Precis Oncol. 2023 Feb;7:e2200361. doi: 10.1200/PO.22.00361.

  PMID: 36848607 DERIVED

• Ho TH, Liu XD, Huang Y, Warneke CL, Johnson MM, Hoang A, Tamboli P, Wang F, Jonasch E. The impact of FGFR1 and FRS2alpha expression on sorafenib treatment in metastatic renal cell carcinoma. BMC Cancer. 2015 Apr 18;15:304. doi: 10.1186/s12885-015-1302-1.

  PMID: 25900027 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Sorafenib; Introns; Interferon alpha-2

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Eric Jonasch, MD/Associate Professor, Genitourinary Medical Oncology
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-2830

Study Officials

• Eric Jonasch

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2005
• First Posted: August 4, 2005
• Study Start: June 1, 2005
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: September 16, 2016
• Results First Posted: September 16, 2016

Record last verified: 2016-07

Locations

US (1)