Brivanib Metastatic Renal Cell Carcinoma

NCT01253668 | Terminated Phase 2 Results DMC

• 1 other identifier: UPCC 04810
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II study of an investigational agent, brivanib, in patients with refractory metastatic renal cell carcinoma. This study will evaluate the safety and effectiveness of brivanib in renal cell carcinoma, and explore the activity of this drug in this population to determine whether imaging and molecular features of the tumors can be used to predict response. Approximately 30 people with advanced kidney cancer will be enrolled on this study at the University of Pennsylvania.

Conditions

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  All patients will be followed through the entire 16-week period and will be given a binary outcome assignment: progressive disease or not.

  16 weeks

Secondary Outcomes (9)

• Best Overall Response Rated for Each Patients as Assessed by RECIST 1.1 Guidelines

  Every 8 weeks

• Overall Survival

  Every 8 weeks

• Change in Total Antibody Binding as Assessed by 124I-cG250 PET/CT Imaging (Correlative Studies)

  At baseline and 8 weeks

• Response Rate for All Patients

  Every 8 weeks

• Molecular Markers

  At baseline

Study Arms (1)

Arm 1

EXPERIMENTAL

Patients receive oral brivanib alaninate daily in the absence of disease progression or unacceptable toxicity.

Drug: Brivanib alaninate; Genetic: Polymerase chain reaction; Other: Iodine I 124 chimeric monoclonal antibody G250; Procedure: Positron emission tomography/computed tomography; Genetic: Protein expression analysis; Other: Immunohistochemistry

Interventions

Brivanib alaninate DRUG

Brivanib by mouth daily at a dose of 800mg.

Arm 1

Polymerase chain reaction GENETIC

Undergo 1241-cG250 PET/CT imaging (correlative studies)

Also known as: PCR

Arm 1

Iodine I 124 chimeric monoclonal antibody G250 OTHER

Undergo 124I-cG250 PET/CT imaging (correlative studies)

Arm 1

Positron emission tomography/computed tomography PROCEDURE

Undergo 1241-cG250 PET/CT imaging (correlative studies)

Arm 1

Protein expression analysis GENETIC

Correlative studies

Arm 1

Immunohistochemistry OTHER

correlative studies

Also known as: immunohistochemistry staining method

Arm 1

Eligibility Criteria

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

You may qualify if:

• Male and female adults with metastatic renal cell carcinoma
• Patients will have tumors that bear a clear cell component that comprises greater than or equal to 50% of the tumor.
• Disease must be measurable in accord with RECIST 1.1 guidelines.
• Patients who have developed progressive disease or intolerance on treatment with sorafenib, sunitinib, bevacizumab, or pazopanib over a 60 day period who have not discontinued this therapy more than 100 days prior to study enrollment. Progressive disease per RECIST 1.1 guidelines will be preferred
• Therapy with up to three prior systemic regimens will be allowed.
• Patients may have been treated with any of the following: sorafenib, sunitinib, bevacizumab, pazopanib, temsirolimus, everolimus, interferon alpha, interleuken-2.
• Treatment with up to one prior regimen that included cytotoxic chemotherapy will be allowed.
• Patients may have been treated with more than 1 antiangiogenic therapy (e.g., patients may have been treated with both sorafenib and sunitinib or sunitinib and bevacizumab, or sequential combinations that include pazopanib).
• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Tumor tissue must be available for correlative studies.
• Patients must consent to allow the acquisition of formalin-fixed paraffin-embedded (FFPE) material (block or unstained slides) by study personnel for performance of correlative tissue studies.

You may not qualify if:

• Known brain metastases
• Prior therapy with brivanib, or anti-FGFR (fibroblast growth factor receptor) therapy.
• History of thrombotic or embolic events within the last six months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism.
• Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE version 4.0 Grade greater than 3 within 30 days prior to study entry.
• Uncontrolled or significant cardiovascular disease.
• QTc greater than 450 msec on two consecutive ECGs (Baseline ECG should be repeated if QTc is found to be greater than 450 msec.).
• Active infection, less than 7 days after completing systemic antibiotic therapy.
• History of non-healing wounds or ulcers or bone fractures within 3 months of fracture.
• Major surgical procedure, open biopsy, or significant traumatic injury less than 3 weeks prior to study enrollment or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration)within 1 week prior to study enrollment.
• Cytotoxic chemotherapy within 3 weeks, bevacizumab within 2 months, or radiation therapy within 2 weeks, other targeted therapies (e.g., sorafenib, sunitinib, temsirolimus, everolimus)within 2 days.
• Inability to swallow tablets or untreated malabsorption syndrome.
• Pre-existing thyroid abnormality with thyroid function that cannot be controlled with medication.
• History of HIV
• Patients with centrally cavitating lung lesions.
• Patients requiring therapeutic anticoagulation with warfarin at baseline. However, prophylactic therapy with a low molecular weight heparin at baseline is acceptable.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

brivanib; Polymerase Chain Reaction; Magnetic Resonance Spectroscopy; Immunohistochemistry

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)

Nucleic Acid Amplification Techniques; Genetic Techniques; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Immunologic Techniques

Limitations and Caveats

The study was terminated, and the PI has left the institution. Despite all possible efforts to contact the PI/study team members, no data are available to be reported.

Results Point of Contact

• Title: Dr. Stephen Keefe
• Organization: Merck

stephen.keefe@merck.com

215-220-9693

Study Officials

• Stephen Keefe, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2010
• First Posted: December 3, 2010
• Study Start: November 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: April 13, 2021
• Results First Posted: March 19, 2021

Record last verified: 2021-03

Locations

US (1)