BNC105P in Combination With Everolimus/Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma

Renal Cell Carcinoma Clinical Trial

Official title:

Phase I/II Study of BNC105P in Combination With Everolimus or Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma Following Prior Tyrosine Kinase Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01034631
• Other study ID #: HOG GU09-145
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 2010
• Est. completion date: December 2016

Study information

• Verified date: April 2017
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether BNC105P in combination with/following everolimus is effective in the treatment of progressive metastatic clear cell renal cell carcinoma following prior tyrosine kinase inhibitors.

Description:

OUTLINE: This is a multi-center study. Phase I: Patients will be accrued in the classic 3 patients per dose per cohort design, 21-day cycle - Dose Level 1 Everolimus 10 mg BNC105P 4.2 mg/m2 - Dose Level 2 Everolimus 10 mg BNC105P 8.4 mg/m2 - Dose Level 3 Everolimus 10 mg BNC105P 12.6 mg/m2 - Dose Level 4 Everolimus 10 mg BNC105P 16 mg/m2 Phase II: Patients will be randomized 1:1 to Arm A or Arm B Combination Arm A: Everolimus 10 mg + BNC105P MTD (from Phase 1 study) 21 day cycle Sequential Arm B: Everolimus 10 mg 21 day cycle - Patients to receive BNC105P monotherapy at 16 mg/m2 following progression or intolerable toxicity on everolimus therapy. Karnofsky Performance Score (KPS) ≥70 within 7 days prior to registration for protocol therapy. Life Expectancy: Not specified Hematopoietic: - White blood cell count (WBC) > 3.5 K/mm3 - Hemoglobin (Hgb) > 8.5 g/dL - Platelets > 100 K/mm3 - Absolute neutrophil count (ANC) > 1.5 K/mm3 Hepatic: - Total Bilirubin < 1.25 x ULN - Aminotransferase (AST and ALT) < 2.5 x ULN Renal: - Serum Creatinine < 2.5 x ULN (upper limit normal) Cardiovascular: - No significant cardiovascular events within 6 months (CVA, CAD, peripheral arterial obstruction, arrhythmias, cardiac dysfunction) of registration for protocol therapy - No history of clinical CHF or LVEF <50% by Echo (or MUGA) within 30 days prior to registration for protocol therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological or cytological proof of component (any percent) of clear cell RCC (renal cell carcinoma).
• Metastatic or locally advanced unresectable RCC. NOTE: Prior nephrectomy is not mandatory.
• Progressive disease after 1-2 prior VEGF-directed tyrosine kinase inhibitors (TKIs).
• Measurable disease according to RECIST and obtained by imaging within 30 days prior to registration for protocol therapy.
• Written informed consent and HIPAA authorization for release of personal health information.
• Age > 18 years at the time of consent.
• Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after treatment discontinuation.
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to registration for protocol therapy.

Exclusion Criteria:

• No active brain metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis within 30 days prior to registration on protocol therapy. NOTE: A patient with prior brain metastasis are eligible if they have completed their radiation treatment for brain metastasis =30 days prior to registration for protocol therapy, are off steroids, and are asymptomatic.
• No other currently active malignancy.
• No treatment with any investigational agent within 14 days prior to registration for protocol therapy. NOTE: If treated with investigational agent within 14 days prior to registration, AE must be resolved back to baseline.
• Prior cancer treatment must be completed at least 14 days prior to registration for protocol therapy and the patient must have recovered from the acute toxic effects of the regimen. With the exception of Bevacizumab treatment, which must be completed 30 days prior to registration for protocol therapy.
• Prior radiation therapy to < 25% of the bone marrow [see bone marrow radiation chart in the study procedure manual (SPM)] allowed if completed within 30 days prior to registration for protocol therapy.
• Corrected QT interval (QTc) = 450 msec at least 7 days prior to registration for protocol therapy.
• No clinically significant infections as judged by the treating investigator.
• No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
• No collecting duct, medullary or sarcomatoid histology.
• No prior treatment with temsirolimus or everolimus in the phase II component of the study. NOTE: Prior treatment with these agents is permitted in the phase I component of the study.
• No use of full dose, therapeutic anti-coagulation with warfarin or related anti-coagulants or unfractionated or low molecular weight heparins.
• No uncontrolled hypertension (BP >150/100mmHg despite full doses of 1 anti-hypertensive medication).
• No thrombotic event within 6 months (deep vein thrombosis, pulmonary embolism) of registration for protocol therapy.
• No grade 2 or greater peripheral neuropathy.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• Everolimus
Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals
• BNC105P
BNC105P, up to 16 mg/m^2

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital: Sydney Cancer Centre	Camperdown	New South Wales
Australia	Peninsula Oncology Centre	Frankston	Victoria
Australia	Gallipoli Medical Research Foundation: Greenslopes Private Hospital	Greenslopes	Queensland
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Ashford Cancer Centre	Kurralta Park	South Australia
Australia	Gallipoli Medical Research Foundation: Launceston General Hospital	Launceston	Tasmania
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Sydney Adventist Hospital Ltd.	Wahroonga	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Singapore	National Cancer Centre Singapore	Singapore
United States	New York Oncology Hematology, PC	Albany	New York
United States	Presbyterian Medical Group	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center: Albuquerque	Albuquerque	New Mexico
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Northeast Georgia Cancer Care, LLC	Athens	Georgia
United States	Texas Oncology: Austin North	Austin	Texas
United States	Medical Oncology LLC	Baton Rouge	Louisiana
United States	Texas Oncology: Bedford	Bedford	Texas
United States	Tufts Medical Center	Boston	Massachusetts
United States	Bozeman Deaconness Cancer Center	Bozeman	Montana
United States	Harrison HealthPartners Bremerton Hematology & Oncology	Bremerton	Washington
United States	Cancer Care Centers of Florida: Brooksville	Brooksville	Florida
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Health System: Roy and Patricia Disney Family Cancer Center	Burbank	California
United States	MUSC Hollings Cancer Center	Charleston	South Carolina
United States	Northwestern University, Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	Compassionate Cancer Care Medical Group	Corona	California
United States	Compassionate Cancer Care Medical Group, Inc.	Corona	California
United States	Hematology and Oncology Associates of Rhode Island	Cranston	Rhode Island
United States	Texas Oncology, PA	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Centura Health Research Center	Denver	Colorado
United States	City of Hope	Duarte	California
United States	Dublin Hematology & Oncology Care	Dublin	Georgia
United States	Trinitas Regional Medical Center	Elizabeth	New Jersey
United States	Deaconess Clinic	Evansville	Indiana
United States	Broward Oncology Associates	Fort Lauderdale	Florida
United States	Fort Wayne Oncology & Hematology, Inc	Fort Wayne	Indiana
United States	Texas Oncology: Fort Worth	Fort Worth	Texas
United States	Robert A. Moss, M.D., FACP, Inc.	Fountain Valley	California
United States	California Cancer Associates for Research and Excellence	Fresno	California
United States	University of Florida, Shands Cancer Center	Gainesville	Florida
United States	Medical & Surgical Specialists, LLC	Galesburg	Illinois
United States	The Jones Clinic, PC	Germantown	Tennessee
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Western Oncology & Hematology	Golden	Colorado
United States	IU Health Goshen	Goshen	Indiana
United States	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Sletten Cancer Specialists	Great Falls	Montana
United States	Marin Specialty Care	Greenbrae	California
United States	Kentucky Cancer Clinic	Hazard	Kentucky
United States	South Carolina Cancer Specialists	Hilton Head Island	South Carolina
United States	Genesis Cancer Center	Hot Springs	Arkansas
United States	Houston Cancer Center	Houston	Texas
United States	Methodist Hospital Research Institute	Houston	Texas
United States	Texas Oncology: Houston Memorial City	Houston	Texas
United States	Community Regional Cancer Center	Indianapolis	Indiana
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	IU Health Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Cascade Cancer Center	Kirkland	Washington
United States	Horizon Oncology Research	Lafayette	Indiana
United States	NYU Langone Arena Oncology	Lake Success	New York
United States	Good Samaritan Hospital	Los Angeles	California
United States	UCLA Med - Hematology & Oncology	Los Angeles	California
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Lynchburg Hematology Oncology Clinic, Inc.	Lynchburg	Virginia
United States	Dartmouth-Hitchcock Medical Center	Manchester	New Hampshire
United States	Metairie Oncologists	Metairie	Louisiana
United States	Advanced Pharma CR, LLC	Miami	Florida
United States	Signal Point Clinical Research Center	Middletown	Ohio
United States	University of Wisconsin, Clinical Cancer Center	Milwaukee	Wisconsin
United States	IU Health at Ball Memorial Hospital Cancer Center	Muncie	Indiana
United States	Monroe Medical Associates	Munster	Indiana
United States	Northwest Alabama Cancer Center	Muscle Shoals	Alabama
United States	Cancer Care Centers of Florida	New Port Richey	Florida
United States	Tisch Cancer Institute at Mount Sinai Medical Center	New York	New York
United States	Oncology Hematology Associates of SW Indiana	Newburgh	Indiana
United States	Hematology Oncology Associates of Rockland	Nyack	New York
United States	Ocala Cancer Institute	Ocala	Florida
United States	Mercy Physicians Of Oklahoma	Oklahoma City	Oklahoma
United States	Methodist Cancer Center	Omaha	Nebraska
United States	Purchase Cancer Group	Paducah	Kentucky
United States	First Health of the Carolinas	Pinehurst	North Carolina
United States	Allegheny Cancer Center	Pittsburgh	Pennsylvania
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Compassionate Cancer Care Medical Group	Riverside	California
United States	Mayo Clinic	Rochester	Minnesota
United States	Cancer Care Centers of Brevard	Rockledge	Florida
United States	CTRC at The UT Health Science Center at San Antonio	San Antonio	Texas
United States	Group Health Medical Centers	Seattle	Washington
United States	University of Washington, Seattle Cancer Care Alliance	Seattle	Washington
United States	Siouxland Hematology Oncology Associates, LLP, Nylen Cancer Center	Sioux City	Iowa
United States	Edward H. Kaplan, M.D., & Associates	Skokie	Illinois
United States	Somerset Hematology Oncology Associates	Somerville	New Jersey
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Rockwood Clinic	Spokane	Washington
United States	Willamette Valley Cancer Institute	Springfield	Oregon
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Berks Hematology Oncology Associates	West Reading	Pennsylvania
United States	American Institute of Research	Whittier	California
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Lawrence M. Stallings, M.D.	Wooster	Ohio
United States	Metro Health Cancer Care	Wyoming	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Hoosier Cancer Research Network	Bionomics Limited

Countries where clinical trial is conducted

United States,  Australia,  Singapore, 

References & Publications (3)

John Sarantopoulos, Long H. Dang, Richard C. Lauer, Alexander Starodub, Ralph J. Hauke, Matt D. Galsky, Kathryn A. Bylow, Charles Lance Cowey, David C. Bibby, Gabriel Kremmidiotis, Elizabeth E. Doolin, Tina C. Lavranos, Jose Luis Iglesias, Guru Sonpavde,

Pal S, Azad A, Bhatia S, Drabkin H, Costello B, Sarantopoulos J, Kanesvaran R, Lauer R, Starodub A, Hauke R, Sweeney CJ, Hahn NM, Sonpavde G, Richey S, Breen T, Kremmidiotis G, Leske A, Doolin E, Bibby DC, Simpson J, Iglesias J, Hutson T. A Phase I/II Tri — View Citation

Thomas E. Hutson, Long H. Dang, Richard C. Lauer, Alexander Starodub, Ralph J. Hauke, Matt D. Galsky, Kathryn A. Bylow, Theodore Logan, Charles Lance Cowey, David C. Bibby, Gabriel Kremmidiotis, Elizabeth E. Doolin, Tina C. Lavranos, Guru Sonpavde, Noah M

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: Maximum Tolerated Dose of BNC105P in Combination With Everolimus.	Phase I	Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Primary	Phase I: Toxicities of BNC105P in Combination With Everolimus.	Determine the toxicities of BNC105P in combination with everolimus. Drug-related treatment emergent adverse events by CTCAE grade 2 or greater are reported	Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Primary	Phase II: 6-month Progression Free Survival (PFS) With the Addition of BNC105P to Everolimus.	Improvement in 6-month PFS with the addition of BNC105P to everolimus. Progression is defined using RECIST criteria as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions	6 months
Secondary	Phase I: Response Rate of BNC105P in Combination With Everolimus.	Number of objective responses per RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.	Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Secondary	Geometric Mean Half-life of BNC105 and BNC105P in Combination With Everolimus.	Determine the PK Profile for BN105P in combination with everolimus by calculating the geometric mean half-life of BNC105P	12 months
Secondary	Phase II: Response Rate With Combination Therapy Compared to Everolimus Alone	Objective response is defined as a confirmed CR or PR per RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.	12 months
Secondary	Phase II: Progression Free Survival (PFS) With BNC105P Alone in Patients After Progressing on Everolimus.	Median time to progression for arm P participants who crossed over to BNC105P monotherapy after progression. Progression is defined per RECIST criteria as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions	12 months
Secondary	Phase II: Adverse Events of Everolimus and BNC105P When Administered as a Combination or Sequential Regimen.	Determine adverse events of everolimus and BNC105P when administered as a combination or sequential regimen. Total number of serious and non-serious adverse events for Arm A and Arm B are summarized. Complete adverse event information is supplied in the Adverse Events reporting section.	12 months
Secondary	Phase II: Overall Survival	Determine overall survival probability, up to a maximum of 5 years from registration for protocol therapy.	60 months
Secondary	Exploratory Objective: Correlation of PFS With Biomarkers	Exploratory analysis of serum biomarkers were undertaken to generate a potential signature for response. The correlation with 6 month progression free survival P value for four plasma biomarkers is reported.	6 months

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