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

NCT ID: NCT01034631

Last Updated: 2022-07-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

154 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-31

Study Completion Date

2016-12-31

Brief Summary

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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

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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.

Conditions

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Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Combination Arm A: Everolimus + BNC105P

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

Group Type ACTIVE_COMPARATOR

Everolimus

Intervention Type DRUG

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

BNC105P

Intervention Type DRUG

BNC105P, up to 16 mg/m\^2

Sequential Arm B:Everolimus followed by BNC105P Monotherapy

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.

Group Type ACTIVE_COMPARATOR

Everolimus

Intervention Type DRUG

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

BNC105P

Intervention Type DRUG

BNC105P, up to 16 mg/m\^2

Interventions

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Everolimus

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

Intervention Type DRUG

BNC105P

BNC105P, up to 16 mg/m\^2

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bionomics Limited

INDUSTRY

Sponsor Role collaborator

Hoosier Cancer Research Network

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas Hutson, D.O.

Role: STUDY_CHAIR

Hoosier Cancer Research Network

Locations

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Northwest Alabama Cancer Center

Muscle Shoals, Alabama, United States

Site Status

Genesis Cancer Center

Hot Springs, Arkansas, United States

Site Status

Providence Health System: Roy and Patricia Disney Family Cancer Center

Burbank, California, United States

Site Status

Compassionate Cancer Care Medical Group, Inc.

Corona, California, United States

Site Status

Compassionate Cancer Care Medical Group

Corona, California, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

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

Fountain Valley, California, United States

Site Status

California Cancer Associates for Research and Excellence

Fresno, California, United States

Site Status

Marin Specialty Care

Greenbrae, California, United States

Site Status

Good Samaritan Hospital

Los Angeles, California, United States

Site Status

UCLA Med - Hematology & Oncology

Los Angeles, California, United States

Site Status

Compassionate Cancer Care Medical Group

Riverside, California, United States

Site Status

American Institute of Research

Whittier, California, United States

Site Status

Centura Health Research Center

Denver, Colorado, United States

Site Status

Western Oncology & Hematology

Golden, Colorado, United States

Site Status

Cancer Care Centers of Florida: Brooksville

Brooksville, Florida, United States

Site Status

Broward Oncology Associates

Fort Lauderdale, Florida, United States

Site Status

University of Florida, Shands Cancer Center

Gainesville, Florida, United States

Site Status

Cancer Specialists of North Florida

Jacksonville, Florida, United States

Site Status

Advanced Pharma CR, LLC

Miami, Florida, United States

Site Status

Cancer Care Centers of Florida

New Port Richey, Florida, United States

Site Status

Ocala Cancer Institute

Ocala, Florida, United States

Site Status

Cancer Care Centers of Brevard

Rockledge, Florida, United States

Site Status

Northeast Georgia Cancer Care, LLC

Athens, Georgia, United States

Site Status

Dublin Hematology & Oncology Care

Dublin, Georgia, United States

Site Status

Kootenai Cancer Center

Post Falls, Idaho, United States

Site Status

Northwestern University, Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Medical & Surgical Specialists, LLC

Galesburg, Illinois, United States

Site Status

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

Skokie, Illinois, United States

Site Status

Deaconess Clinic

Evansville, Indiana, United States

Site Status

Fort Wayne Oncology & Hematology, Inc

Fort Wayne, Indiana, United States

Site Status

IU Health Goshen

Goshen, Indiana, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

IU Health Central Indiana Cancer Centers

Indianapolis, Indiana, United States

Site Status

Community Regional Cancer Center

Indianapolis, Indiana, United States

Site Status

Horizon Oncology Research

Lafayette, Indiana, United States

Site Status

IU Health at Ball Memorial Hospital Cancer Center

Muncie, Indiana, United States

Site Status

Monroe Medical Associates

Munster, Indiana, United States

Site Status

Oncology Hematology Associates of SW Indiana

Newburgh, Indiana, United States

Site Status

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Site Status

Siouxland Hematology Oncology Associates, LLP, Nylen Cancer Center

Sioux City, Iowa, United States

Site Status

Cancer Center of Kansas

Wichita, Kansas, United States

Site Status

Kentucky Cancer Clinic

Hazard, Kentucky, United States

Site Status

Purchase Cancer Group

Paducah, Kentucky, United States

Site Status

Medical Oncology LLC

Baton Rouge, Louisiana, United States

Site Status

Metairie Oncologists

Metairie, Louisiana, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

St. Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Site Status

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

Site Status

Metro Health Cancer Care

Wyoming, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Bozeman Deaconness Cancer Center

Bozeman, Montana, United States

Site Status

Sletten Cancer Specialists

Great Falls, Montana, United States

Site Status

Methodist Cancer Center

Omaha, Nebraska, United States

Site Status

Dartmouth-Hitchcock Medical Center

Manchester, New Hampshire, United States

Site Status

Trinitas Regional Medical Center

Elizabeth, New Jersey, United States

Site Status

Somerset Hematology Oncology Associates

Somerville, New Jersey, United States

Site Status

Presbyterian Medical Group

Albuquerque, New Mexico, United States

Site Status

University of New Mexico Cancer Center: Albuquerque

Albuquerque, New Mexico, United States

Site Status

New York Oncology Hematology, PC

Albany, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

NYU Langone Arena Oncology

Lake Success, New York, United States

Site Status

Tisch Cancer Institute at Mount Sinai Medical Center

New York, New York, United States

Site Status

Hematology Oncology Associates of Rockland

Nyack, New York, United States

Site Status

First Health of the Carolinas

Pinehurst, North Carolina, United States

Site Status

Signal Point Clinical Research Center

Middletown, Ohio, United States

Site Status

Lawrence M. Stallings, M.D.

Wooster, Ohio, United States

Site Status

Mercy Physicians Of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

Willamette Valley Cancer Institute

Springfield, Oregon, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Gettysburg Cancer Center

Gettysburg, Pennsylvania, United States

Site Status

Allegheny Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Mount Nittany Medical Center

State College, Pennsylvania, United States

Site Status

Berks Hematology Oncology Associates

West Reading, Pennsylvania, United States

Site Status

Hematology and Oncology Associates of Rhode Island

Cranston, Rhode Island, United States

Site Status

MUSC Hollings Cancer Center

Charleston, South Carolina, United States

Site Status

South Carolina Cancer Specialists

Hilton Head Island, South Carolina, United States

Site Status

The Jones Clinic, PC

Germantown, Tennessee, United States

Site Status

Texas Oncology: Austin North

Austin, Texas, United States

Site Status

Texas Oncology: Bedford

Bedford, Texas, United States

Site Status

Texas Oncology, PA

Dallas, Texas, United States

Site Status

Texas Oncology: Fort Worth

Fort Worth, Texas, United States

Site Status

Texas Oncology: Houston Memorial City

Houston, Texas, United States

Site Status

Methodist Hospital Research Institute

Houston, Texas, United States

Site Status

Houston Cancer Center

Houston, Texas, United States

Site Status

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, United States

Site Status

CTRC at The UT Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Lynchburg Hematology Oncology Clinic, Inc.

Lynchburg, Virginia, United States

Site Status

Harrison HealthPartners Bremerton Hematology & Oncology

Bremerton, Washington, United States

Site Status

Cascade Cancer Center

Kirkland, Washington, United States

Site Status

Group Health Medical Centers

Seattle, Washington, United States

Site Status

University of Washington, Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Rockwood Clinic

Spokane, Washington, United States

Site Status

University of Wisconsin, Clinical Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Royal Prince Alfred Hospital: Sydney Cancer Centre

Camperdown, New South Wales, Australia

Site Status

Prince of Wales Hospital

Randwick, New South Wales, Australia

Site Status

Sydney Adventist Hospital Ltd.

Wahroonga, New South Wales, Australia

Site Status

Gallipoli Medical Research Foundation: Greenslopes Private Hospital

Greenslopes, Queensland, Australia

Site Status

Royal Brisbane & Women's Hospital

Herston, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Ashford Cancer Centre

Kurralta Park, South Australia, Australia

Site Status

Gallipoli Medical Research Foundation: Launceston General Hospital

Launceston, Tasmania, Australia

Site Status

Peninsula Oncology Centre

Frankston, Victoria, Australia

Site Status

Austin Hospital

Heidelberg, Victoria, Australia

Site Status

Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

National Cancer Centre Singapore

Singapore, , Singapore

Site Status

Countries

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United States Australia Singapore

References

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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

Reference Type 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

Reference Type 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.

Reference Type RESULT
PMID: 25788492 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34108261 (View on PubMed)

Related Links

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http://www.hoosiercancer.org

Hoosier Cancer Research Network Homepage

Other Identifiers

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HOG GU09-145

Identifier Type: -

Identifier Source: org_study_id

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