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

NCT01034631 | Completed Phase 1 Results DMC

• 1 other identifier: HOG GU09-145
• Study Type: interventional
• Target: 154
• Locations: 3 countries
• Sites: 108

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.

Conditions

Renal Cell Carcinoma

Keywords

Metastatic Kidney Cancer; BNC105P

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (7)

• Phase I: Response Rate of BNC105P in Combination With Everolimus.

  Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months

• Geometric Mean Half-life of BNC105 and BNC105P in Combination With Everolimus.

  12 months

• Phase II: Response Rate With Combination Therapy Compared to Everolimus Alone

  12 months

• Phase II: Progression Free Survival (PFS) With BNC105P Alone in Patients After Progressing on Everolimus.

  12 months

• Phase II: Adverse Events of Everolimus and BNC105P When Administered as a Combination or Sequential Regimen.

  12 months

Study Arms (2)

Combination Arm A: Everolimus + BNC105P

ACTIVE COMPARATOR

Combination Arm A: Everolimus 10 mg, BNC105P MTD (from Phase 1 study) 21 day cycle

Drug: Everolimus; Drug: BNC105P

Sequential Arm B:Everolimus followed by BNC105P Monotherapy

ACTIVE COMPARATOR

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.

Drug: Everolimus; Drug: BNC105P

Interventions

Everolimus DRUG

Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals

Combination Arm A: Everolimus + BNC105P; Sequential Arm B:Everolimus followed by BNC105P Monotherapy

BNC105P DRUG

BNC105P, up to 16 mg/m\^2

Combination Arm A: Everolimus + BNC105P; Sequential Arm B:Everolimus followed by BNC105P Monotherapy

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoosier Cancer Research Network: lead
• Bionomics Limited: collaborator

Study Sites (108)

Northwest Alabama Cancer Center

Muscle Shoals, Alabama, 35661, United States

Location

Genesis Cancer Center

Hot Springs, Arkansas, 71913, United States

Location

Providence Health System: Roy and Patricia Disney Family Cancer Center

Burbank, California, 91505, United States

Location

Compassionate Cancer Care Medical Group, Inc.

Corona, California, 92879, United States

Location

Compassionate Cancer Care Medical Group

Corona, California, 92879, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Robert A. Moss, M.D., FACP, Inc.

Fountain Valley, California, 92708, United States

Location

California Cancer Associates for Research and Excellence

Fresno, California, 93720, United States

Location

Marin Specialty Care

Greenbrae, California, 94904, United States

Location

Good Samaritan Hospital

Los Angeles, California, 90017, United States

Location

UCLA Med - Hematology & Oncology

Los Angeles, California, 90095, United States

Location

Compassionate Cancer Care Medical Group

Riverside, California, 92501, United States

Location

American Institute of Research

Whittier, California, 90603, United States

Location

Centura Health Research Center

Denver, Colorado, 80210, United States

Location

Western Oncology & Hematology

Golden, Colorado, 80401, United States

Location

Cancer Care Centers of Florida: Brooksville

Brooksville, Florida, 34613, United States

Location

Broward Oncology Associates

Fort Lauderdale, Florida, 33308, United States

Location

University of Florida, Shands Cancer Center

Gainesville, Florida, 32610, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

Location

Advanced Pharma CR, LLC

Miami, Florida, 33136, United States

Location

Cancer Care Centers of Florida

New Port Richey, Florida, 34652, United States

Location

Ocala Cancer Institute

Ocala, Florida, 34471, United States

Location

Cancer Care Centers of Brevard

Rockledge, Florida, 32955, United States

Location

Northeast Georgia Cancer Care, LLC

Athens, Georgia, 30607, United States

Location

Dublin Hematology & Oncology Care

Dublin, Georgia, 31021, United States

Location

Kootenai Cancer Center

Post Falls, Idaho, 83854, United States

Location

Northwestern University, Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

Medical & Surgical Specialists, LLC

Galesburg, Illinois, 61401, United States

Location

Edward H. Kaplan, M.D., & Associates

Skokie, Illinois, 60076, United States

Location

Deaconess Clinic

Evansville, Indiana, 47713, United States

Location

Fort Wayne Oncology & Hematology, Inc

Fort Wayne, Indiana, 46815, United States

Location

IU Health Goshen

Goshen, Indiana, 46527, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

IU Health Central Indiana Cancer Centers

Indianapolis, Indiana, 46219, United States

Location

Community Regional Cancer Center

Indianapolis, Indiana, 46256, United States

Location

Horizon Oncology Research

Lafayette, Indiana, 47905, United States

Location

IU Health at Ball Memorial Hospital Cancer Center

Muncie, Indiana, 47303, United States

Location

Monroe Medical Associates

Munster, Indiana, 46321, United States

Location

Oncology Hematology Associates of SW Indiana

Newburgh, Indiana, 47630, United States

Location

Northern Indiana Cancer Research Consortium

South Bend, Indiana, 46601, United States

Location

Siouxland Hematology Oncology Associates, LLP, Nylen Cancer Center

Sioux City, Iowa, 51101, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

Kentucky Cancer Clinic

Hazard, Kentucky, 41701, United States

Location

Purchase Cancer Group

Paducah, Kentucky, 42001, United States

Location

Medical Oncology LLC

Baton Rouge, Louisiana, 70809, United States

Location

Metairie Oncologists

Metairie, Louisiana, 70006, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

St. Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

Location

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49546, United States

Location

Metro Health Cancer Care

Wyoming, Michigan, 49519, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Bozeman Deaconness Cancer Center

Bozeman, Montana, 59715, United States

Location

Sletten Cancer Specialists

Great Falls, Montana, 59405, United States

Location

Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

Dartmouth-Hitchcock Medical Center

Manchester, New Hampshire, 03102, United States

Location

Trinitas Regional Medical Center

Elizabeth, New Jersey, 07202, United States

Location

Somerset Hematology Oncology Associates

Somerville, New Jersey, 08876, United States

Location

Presbyterian Medical Group

Albuquerque, New Mexico, 87110, United States

Location

University of New Mexico Cancer Center: Albuquerque

Albuquerque, New Mexico, 87131, United States

Location

New York Oncology Hematology, PC

Albany, New York, 12208, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

NYU Langone Arena Oncology

Lake Success, New York, 11042, United States

Location

Tisch Cancer Institute at Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Hematology Oncology Associates of Rockland

Nyack, New York, 10960, United States

Location

First Health of the Carolinas

Pinehurst, North Carolina, 28374, United States

Location

Signal Point Clinical Research Center

Middletown, Ohio, 45042, United States

Location

Lawrence M. Stallings, M.D.

Wooster, Ohio, 44691, United States

Location

Mercy Physicians Of Oklahoma

Oklahoma City, Oklahoma, 73120, United States

Location

Willamette Valley Cancer Institute

Springfield, Oregon, 97477, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Gettysburg Cancer Center

Gettysburg, Pennsylvania, 17235, United States

Location

Allegheny Cancer Center

Pittsburgh, Pennsylvania, 15212, United States

Location

Mount Nittany Medical Center

State College, Pennsylvania, 16803, United States

Location

Berks Hematology Oncology Associates

West Reading, Pennsylvania, 19611, United States

Location

Hematology and Oncology Associates of Rhode Island

Cranston, Rhode Island, 02920, United States

Location

MUSC Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

South Carolina Cancer Specialists

Hilton Head Island, South Carolina, 29926, United States

Location

The Jones Clinic, PC

Germantown, Tennessee, 38138, United States

Location

Texas Oncology: Austin North

Austin, Texas, 78758, United States

Location

Texas Oncology: Bedford

Bedford, Texas, 76022, United States

Location

Texas Oncology, PA

Dallas, Texas, 75246, United States

Location

Texas Oncology: Fort Worth

Fort Worth, Texas, 76104, United States

Location

Texas Oncology: Houston Memorial City

Houston, Texas, 77024, United States

Location

Methodist Hospital Research Institute

Houston, Texas, 77030, United States

Location

Houston Cancer Center

Houston, Texas, 77055, United States

Location

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, 79410, United States

Location

CTRC at The UT Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Lynchburg Hematology Oncology Clinic, Inc.

Lynchburg, Virginia, 24501, United States

Location

Harrison HealthPartners Bremerton Hematology & Oncology

Bremerton, Washington, 98310, United States

Location

Cascade Cancer Center

Kirkland, Washington, 98034, United States

Location

Group Health Medical Centers

Seattle, Washington, 98109, United States

Location

University of Washington, Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Rockwood Clinic

Spokane, Washington, 99204, United States

Location

University of Wisconsin, Clinical Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Royal Prince Alfred Hospital: Sydney Cancer Centre

Camperdown, New South Wales, 2050, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Sydney Adventist Hospital Ltd.

Wahroonga, New South Wales, 2076, Australia

Location

Gallipoli Medical Research Foundation: Greenslopes Private Hospital

Greenslopes, Queensland, 4120, Australia

Location

Royal Brisbane & Women's Hospital

Herston, Queensland, 4029, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4201, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Ashford Cancer Centre

Kurralta Park, South Australia, 5037, Australia

Location

Gallipoli Medical Research Foundation: Launceston General Hospital

Launceston, Tasmania, 7250, Australia

Location

Peninsula Oncology Centre

Frankston, Victoria, 3199, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Related Publications (4)

• 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

  RESULT

• 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

  RESULT

• 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.

  PMID: 25788492 RESULT

• 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.

  PMID: 34108261 DERIVED

Related Links

• Hoosier Cancer Research Network Homepage

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

Everolimus; BNC 105P

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Clinical Data Coordinator
• Organization: Hoosier Cancer Research Network, Inc.

jsmith@hoosiercancer.org

317-921-2050

Study Officials

• Thomas Hutson, D.O.

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2009
• First Posted: December 17, 2009
• Study Start: January 1, 2010
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: July 11, 2022
• Results First Posted: May 24, 2017

Record last verified: 2017-04

Locations

AU (13); US (94); SG (1)