Clinical trial NCT01034631: BNC105P in Combination With Everolimus/Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Renal Cell Carcinoma
Keywords: Metastatic Kidney Cancer
BNC105P
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Bionomics Limited
First posted: 2009-12-17
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase I: Maximum Tolerated Dose of BNC105P in Combination With Everolimus.
timeFrame: Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
measure: Phase I: Toxicities of BNC105P in Combination With Everolimus.
timeFrame: Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
measure: Phase II: 6-month Progression Free Survival (PFS) With the Addition of BNC105P to Everolimus.
timeFrame: 6 months
Secondary outcomes:
measure: Phase I: Response Rate of BNC105P in Combination With Everolimus.
timeFrame: Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
measure: Geometric Mean Half-life of BNC105 and BNC105P in Combination With Everolimus.
timeFrame: 12 months
measure: Phase II: Response Rate With Combination Therapy Compared to Everolimus Alone
timeFrame: 12 months
measure: Phase II: Progression Free Survival (PFS) With BNC105P Alone in Patients After Progressing on Everolimus.
timeFrame: 12 months
measure: Phase II: Adverse Events of Everolimus and BNC105P When Administered as a Combination or Sequential Regimen.
timeFrame: 12 months
measure: Phase II: Overall Survival
timeFrame: 60 months
measure: Exploratory Objective: Correlation of PFS With Biomarkers
timeFrame: 6 months
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
facility: Northwest Alabama Cancer Center
state: Alabama
city: Hot Springs
country: United States
facility: Genesis Cancer Center
state: Arkansas
city: Burbank
country: United States
facility: Providence Health System: Roy and Patricia Disney Family Cancer Center
state: California
city: Corona
country: United States
facility: Compassionate Cancer Care Medical Group, Inc.
state: California
city: Corona
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Fountain Valley
country: United States
facility: Robert A. Moss, M.D., FACP, Inc.
state: California
city: Fresno
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: Greenbrae
country: United States
facility: Marin Specialty Care
state: California
city: Los Angeles
country: United States
facility: Good Samaritan Hospital
state: California
city: Los Angeles
country: United States
facility: UCLA Med - Hematology & Oncology
state: California
city: Riverside
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: Denver
country: United States
facility: Centura Health Research Center
state: Colorado
city: Golden
country: United States
facility: Western Oncology & Hematology
state: Colorado
city: Brooksville
country: United States
facility: Cancer Care Centers of Florida: Brooksville
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward Oncology Associates
state: Florida
city: Gainesville
country: United States
facility: University of Florida, Shands Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Miami
country: United States
facility: Advanced Pharma CR, LLC
state: Florida
city: New Port Richey
country: United States
facility: Cancer Care Centers of Florida
state: Florida
city: Ocala
country: United States
facility: Ocala Cancer Institute
state: Florida
city: Rockledge
country: United States
facility: Cancer Care Centers of Brevard
state: Florida
city: Athens
country: United States
facility: Northeast Georgia Cancer Care, LLC
state: Georgia
city: Dublin
country: United States
facility: Dublin Hematology & Oncology Care
state: Georgia
city: Post Falls
country: United States
facility: Kootenai Cancer Center
state: Idaho
city: Chicago
country: United States
facility: Northwestern University, Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Galesburg
country: United States
facility: Medical & Surgical Specialists, LLC
state: Illinois
city: Skokie
country: United States
facility: Edward H. Kaplan, M.D., & Associates
state: Illinois
city: Evansville
country: United States
facility: Deaconess Clinic
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Oncology & Hematology, Inc
state: Indiana
city: Goshen
country: United States
facility: IU Health Goshen
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: IU Health Central Indiana Cancer Centers
state: Indiana
city: Indianapolis
country: United States
facility: Community Regional Cancer Center
state: Indiana
city: Lafayette
country: United States
facility: Horizon Oncology Research
state: Indiana
city: Muncie
country: United States
facility: IU Health at Ball Memorial Hospital Cancer Center
state: Indiana
city: Munster
country: United States
facility: Monroe Medical Associates
state: Indiana
city: Newburgh
country: United States
facility: Oncology Hematology Associates of SW Indiana
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Sioux City
country: United States
facility: Siouxland Hematology Oncology Associates, LLP, Nylen Cancer Center
state: Iowa
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Hazard
country: United States
facility: Kentucky Cancer Clinic
state: Kentucky
city: Paducah
country: United States
facility: Purchase Cancer Group
state: Kentucky
city: Baton Rouge
country: United States
facility: Medical Oncology LLC
state: Louisiana
city: Metairie
country: United States
facility: Metairie Oncologists
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer and Hematology Centers of Western Michigan
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Cancer Care
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Bozeman
country: United States
facility: Bozeman Deaconness Cancer Center
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Specialists
state: Montana
city: Omaha
country: United States
facility: Methodist Cancer Center
state: Nebraska
city: Manchester
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Elizabeth
country: United States
facility: Trinitas Regional Medical Center
state: New Jersey
city: Somerville
country: United States
facility: Somerset Hematology Oncology Associates
state: New Jersey
city: Albuquerque
country: United States
facility: Presbyterian Medical Group
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center: Albuquerque
state: New Mexico
city: Albany
country: United States
facility: New York Oncology Hematology, PC
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Lake Success
country: United States
facility: NYU Langone Arena Oncology
state: New York
city: New York
country: United States
facility: Tisch Cancer Institute at Mount Sinai Medical Center
state: New York
city: Nyack
country: United States
facility: Hematology Oncology Associates of Rockland
state: New York
city: Pinehurst
country: United States
facility: First Health of the Carolinas
state: North Carolina
city: Middletown
country: United States
facility: Signal Point Clinical Research Center
state: Ohio
city: Wooster
country: United States
facility: Lawrence M. Stallings, M.D.
state: Ohio
city: Oklahoma City
country: United States
facility: Mercy Physicians Of Oklahoma
state: Oklahoma
city: Springfield
country: United States
facility: Willamette Valley Cancer Institute
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Gettysburg
country: United States
facility: Gettysburg Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: West Reading
country: United States
facility: Berks Hematology Oncology Associates
state: Pennsylvania
city: Cranston
country: United States
facility: Hematology and Oncology Associates of Rhode Island
state: Rhode Island
city: Charleston
country: United States
facility: MUSC Hollings Cancer Center
state: South Carolina
city: Hilton Head Island
country: United States
facility: South Carolina Cancer Specialists
state: South Carolina
city: Germantown
country: United States
facility: The Jones Clinic, PC
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology: Austin North
state: Texas
city: Bedford
country: United States
facility: Texas Oncology: Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, PA
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology: Fort Worth
state: Texas
city: Houston
country: United States
facility: Texas Oncology: Houston Memorial City
state: Texas
city: Houston
country: United States
facility: Methodist Hospital Research Institute
state: Texas
city: Houston
country: United States
facility: Houston Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: San Antonio
country: United States
facility: CTRC at The UT Health Science Center at San Antonio
state: Texas
city: Lynchburg
country: United States
facility: Lynchburg Hematology Oncology Clinic, Inc.
state: Virginia
city: Bremerton
country: United States
facility: Harrison HealthPartners Bremerton Hematology & Oncology
state: Washington
city: Kirkland
country: United States
facility: Cascade Cancer Center
state: Washington
city: Seattle
country: United States
facility: Group Health Medical Centers
state: Washington
city: Seattle
country: United States
facility: University of Washington, Seattle Cancer Care Alliance
state: Washington
city: Spokane
country: United States
facility: Rockwood Clinic
state: Washington
city: Milwaukee
country: United States
facility: University of Wisconsin, Clinical Cancer Center
state: Wisconsin
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital: Sydney Cancer Centre
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Wahroonga
country: Australia
facility: Sydney Adventist Hospital Ltd.
state: New South Wales
city: Greenslopes
country: Australia
facility: Gallipoli Medical Research Foundation: Greenslopes Private Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre
state: South Australia
city: Launceston
country: Australia
facility: Gallipoli Medical Research Foundation: Launceston General Hospital
state: Tasmania
city: Frankston
country: Australia
facility: Peninsula Oncology Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
Study officials:
affiliation: Hoosier Cancer Research Network
name: Thomas Hutson, D.O.
role: STUDY_CHAIR
References:
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. Hahn, Christopher Sweeney, John Sarantopoulos. Phase I results of a phase I/II trial of BNC105P with everolimus in metastatic renal cell carcinoma (mRCC) patients previously treated with VEGFR tyrosine kinase inhibitors. J Clin Oncol 30, 2012 (suppl; abstr 4603) http://www.asco.org/ASCOv2/Meetings/Abstracts&vmview=abst_detail_view&confID=114&abstractID=91911
citation: 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, Theodore Logan, Noah M. Hahn, Christopher Sweeney, Thomas E. Hutson. A phase I/II trial of BNC105P with everolimus in metastatic renal cell carcinoma (mRCC) patients: Updated phase I results of the Disruptor-1 trial. J Clin Oncol 31, 2013 (suppl; abstr 4563. http://abstracts2.asco.org/AbstView_132_107981.html
citation: 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 Trial of BNC105P with Everolimus in Metastatic Renal Cell Carcinoma. Clin Cancer Res. 2015 Aug 1;21(15):3420-7. doi: 10.1158/1078-0432.CCR-14-3370. Epub 2015 Mar 18.
citation: Yang ES, Nassar AH, Adib E, Jegede OA, Alaiwi SA, Manna DLD, Braun DA, Zarei M, Du H, Pal SK, Naik G, Sonpavde GP. Gene Expression Signature Correlates with Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with Everolimus Alone or with a Vascular Disrupting Agent. Mol Cancer Ther. 2021 Aug;20(8):1454-1461. doi: 10.1158/1535-7163.MCT-20-1091. Epub 2021 Jun 9.