Sorafenib Tosylate and Bevacizumab in Treating Patients With Advanced Kidney Cancer

NCT00126503 | Completed Phase 1 Results

• 6 other identifiers: NCI-2009-00066CDR0000434814URO 4706555U01CA099177P30CA068485
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 5

Brief Summary

This phase I/II trial studies the side effects and best dose of sorafenib tosylate and bevacizumab and to see how well they work in treating patients with advanced kidney cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth by targeting certain cells. Bevacizumab and sorafenib tosylate may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib tosylate together with bevacizumab may kill more tumor cells.

Conditions

Chromophobe Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Papillary Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Stage IV Renal Cell Cancer

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) of BAY 43-9006 (Sorafenib)in Combination With Bevacizumab (Phase I)

  The highest dose in milligrams (mg) of BAY 43-9006 (Sorafenib) in combination with Bevacizumab while maintaining tolerability. Cohorts of 3-6 patients received escalating doses of sorafenib and bevacizumab until the maximum tolerated dose (MTD) was achieved. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity during the initial cycle of therapy. DLTs include absolute neutrophil count (ANC) \< 500/mm3 for \> 7 days, ANC \< 1000/mm3 with fever \> 101 degrees Fahrenheit, platelet count \< 50,000 mm3, and non-hematologic toxicity Common Toxicity Criteria (CTC) \>= Grade 3.

  at 28 days

• Maximum Tolerated Dose of Bevacizumab in Combination With BAY 43-9006 (Sorafenib)(Phase I)

  The highest dose in milligrams (mg) of Bevacizumab in combination with BAY 43-9006 (Sorafenib) while maintaining tolerability. Cohorts of 3-6 patients received escalating doses of sorafenib and bevacizumab until the maximum tolerated dose (MTD) was achieved. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity during the initial cycle of therapy. DLTs include absolute neutrophil count (ANC) \< 500/mm3 for \> 7 days, ANC \< 1000/mm3 with fever \> 101 degrees Fahrenheit, platelet count \< 50,000 mm3, and non-hematologic toxicity Common Toxicity Criteria (CTC) \>= Grade 3.

  at 28 days

• Objective Response

  Objective response as determined by RECIST v. 1.0 (measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) \> 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) \> 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions)or last date known alive

  Every 8 weeks to date of progression

Secondary Outcomes (2)

• Overall Survival

  on-study to date of expired or last date known alive

• Progression-free Survival

  on-study to date of progression or last date known alive without progression

Study Arms (1)

Treatment (bevacizumab and sorafenib tosylate)

EXPERIMENTAL

Phase I: Patients receive sorafenib PO twice daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of sorafenib and bevacizumab until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD. Phase II: Patients receive sorafenib PO once daily on days 1-28 and bevacizumab IV over 90 minutes on days 1 and 15 at the MTD in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab; Drug: Sorafenib Tosylate; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Avastin, rhuMab-VEGF

Treatment (bevacizumab and sorafenib tosylate)

Sorafenib Tosylate DRUG

Given PO

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

Treatment (bevacizumab and sorafenib tosylate)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (bevacizumab and sorafenib tosylate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (bevacizumab and sorafenib tosylate)

Eligibility Criteria

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

You may qualify if:

• PHASE I ELIGIBILITY CRITERIA
• Patients must have histological or cytological confirmation of renal cell carcinoma (clear cell, papillary, chromophobe, or sarcomatoid) not curable by standard approaches; tumor must be measurable by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; nephrectomy prior to enrollment is not required
• Patients may not have had prior therapy with inhibitors of the mitogen-activated protein (MAP) kinase pathway or inhibitors of VEGF and/or its receptor signaling (VEGFR2)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of greater than 3 months
• Hemoglobin (Hgb) \>= 9.0gm/dl (transfusions allowed prior to enrollment)
• White Blood Count \>= 3,000/mm\^3
• Absolute Granulocyte Count \>= 1,200/mm\^3
• Platelet Count \>= 100,000/mm\^3
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) \>= 40ml/min (neither drug is cleared by the kidney)
• Total Bilirubin =\< 1.5 x ULN
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN
• International normalized ratio (INR) =\< 1.5 and activated partial thromboplastin time (aPTT) that is not greater than 1.3 times the ULN
• Urine Dipstick must show less then 1+ protein in urine or the patient will require 24 hour urine collection with total protein =\< 1000 mg/24 hour
• 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 while participating in this study, she should inform her treating physician immediately

You may not qualify if:

• History or clinical evidence of central nervous system (CNS) disease, including primary brain tumor (participants with a history of meningioma are not excluded), seizures not controlled with standard medical therapy, any brain metastasis, or history of stroke within the prior 12 months; patients who have had a history of brain metastasis that have been resected or have had radiosurgery with no progression for more than 6 months are eligible if the Principle Investigator from the coordinating center is consulted and agrees
• Patients entered onto the phase II study may not have received more than one chemotherapy or immunotherapy regimen for Stage IV disease
• Patients may not have received chemotherapy or immunotherapy within 4 weeks of initiating treatment; patients will not have received a regimen containing a monoclonal antibody within 8 weeks of initiating treatment; toxicities from radiation must have resolved and a minimum of two weeks must pass prior to enrollment
• Patients may not have had prior anti-angiogenic therapy including, Sunitinib, VEGF Trap; prior Temsirilomus, Everolimus, Bevacizumab and Sorafenib will not be allowed; thalidomide or interferon (IFN) alpha are allowed either for adjuvant therapy or stage IV disease
• History of allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to Sorafenib
• History of bleeding diathesis or coagulopathy
• A condition that impairs patient's ability to swallow pills will make patient ineligible
• No major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to initiation of therapy on trial
• Anticipation of the need for major surgery during the course of the study
• Current or recent use (within 7 days of starting the study drugs) of full-dose of anticoagulants (except as required to maintain patency of preexisting, permanent indwelling IV catheters or for deep vein thrombosis \[DVT\] prophylaxis, for subjects receiving warfarin, INR should be =\< 1.5) or thrombolytic agent
• Patients with uncontrolled hypertension; blood pressure must be =\< 150/90 mmHg at the time of enrollment on a stable antihypertensive regimen
• Patients with clinically significant cardiovascular disease within 1 year prior to study entry
• Uncontrolled hypertension
• Myocardial infarction or unstable angina \< 6 months prior to registration
• New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication (participants with controlled atrial arrhythmias are not excluded), unstable angina pectoris

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Harvard Cancer Center

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Bevacizumab; Sorafenib

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; 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

Limitations and Caveats

To depict results of this Phases I/II study accurately, each phase was entered as an ARM to enable separation of the data by phase. Events reported in the Adverse Event and Serious Adverse Event sections include AEs and SAEs from Phase I and Phase II

Results Point of Contact

• Title: Jeffrey Sosman, MD
• Organization: Vanderbilt-Ingram Cancer Center

jeff.sosman@vanderbilt.edu

615-936-3048

Study Officials

• Jeffrey Sosman

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2005
• First Posted: August 4, 2005
• Study Start: May 1, 2005
• Primary Completion: October 1, 2011
• Study Completion: February 1, 2012
• Last Updated: January 15, 2015
• Results First Posted: June 28, 2013

Record last verified: 2014-09

Locations

US (5)