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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bionomics Limited
Information provided by (Responsible Party):
Hoosier Oncology Group
ClinicalTrials.gov Identifier:
NCT01034631
First received: December 15, 2009
Last updated: September 12, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: Everolimus
Drug: BNC105P
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoosier Oncology Group:

Primary Outcome Measures:
  • Phase I: To determine maximum tolerated dose and toxicities of BNC105P in combination with everolimus. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Phase II: Improvement in 6-month PFS with the addition of BNC105P to everolimus. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase I: To determine the response rate of BNC105P in combination with everolimus. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Phase I: To evaluate the pharmacokinetic (PK) profile for BNC105P in combination with everolimus [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Phase II: To determine response rate with combination therapy compared to everolimus alone [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Phase II: To determine PFS with BNC105P alone in patients progressing on everolimus. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Phase II: To evaluate the adverse events of the everolimus and BNC105P when administered as a combination or sequential regimen. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Phase II: To determine the overall survival, up to a maximum of 5 years from registration for protocol therapy. [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  • Exploratory Objective: To determine the correlation of PFS with biomarkers [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 152
Study Start Date: January 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Combination Arm A: Everolimus + BNC105P
Combination Arm A: Everolimus 10 mg, BNC105P MTD (from Phase 1 study) 21 day cycle
Drug: Everolimus
Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals
Drug: BNC105P
MTD as determined by Phase I portion
Active Comparator: Sequential Arm B: Everolimus Alone

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
Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals
Drug: BNC105P
Patients to receive BNC105P monotherapy - 16 mg/m2 following progression on everolimus therapy.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01034631

  Hide Study Locations
Locations
United States, Alabama
Northwest Alabama Cancer Center
Muscle Shoals, Alabama, United States, 35661
United States, Arkansas
Genesis Cancer Center
Hot Springs, Arkansas, United States, 71913
United States, California
Providence Health System: Roy and Patricia Disney Family Cancer Center
Burbank, California, United States, 91505
Compassionate Cancer Care Medical Group, Inc.
Corona, California, United States, 92879
Compassionate Cancer Care Medical Group
Corona, California, United States, 92879
City of Hope
Duarte, California, United States, 91010
Robert A. Moss, M.D., FACP, Inc.
Fountain Valley, California, United States, 92708
California Cancer Associates for Research and Excellence
Fresno, California, United States, 93720
Marin Specialty Care
Greenbrae, California, United States, 94904
UCLA Med - Hematology & Oncology
Los Angeles, California, United States, 90095
Good Samaritan Hospital
Los Angeles, California, United States, 90017
Compassionate Cancer Care Medical Group
Riverside, California, United States, 92501
American Institute of Research
Whittier, California, United States, 90603
United States, Colorado
Centura Health Research Center
Denver, Colorado, United States, 80210
Western Oncology & Hematology
Golden, Colorado, United States, 80401
United States, Florida
Cancer Care Centers of Florida: Brooksville
Brooksville, Florida, United States, 34613
Broward Oncology Associates
Ft Lauderdale, Florida, United States, 33308
University of Florida, Shands Cancer Center
Gainesville, Florida, United States, 32610
Cancer Specialists of North Florida
Jacksonville, Florida, United States, 32256
Advanced Pharma CR, LLC
Miami, Florida, United States, 33136
Cancer Care Centers of Florida
New Port Richey, Florida, United States, 34652
Ocala Cancer Institute
Ocala, Florida, United States, 34471
Cancer Care Centers of Brevard
Rockledge, Florida, United States, 32955
United States, Georgia
Northeast Georgia Cancer Care, LLC
Athens, Georgia, United States, 30607
Dublin Hematology & Oncology Care
Dublin, Georgia, United States, 31021
United States, Idaho
Kootenai Cancer Center
Post Falls, Idaho, United States, 83854
United States, Illinois
Northwestern University, Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, United States, 60611
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States, 61401
Edward H. Kaplan, M.D., & Associates
Skokie, Illinois, United States, 60076
United States, Indiana
Deaconess Clinic
Evansville, Indiana, United States, 47713
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, United States, 46815
IU Health Goshen
Goshen, Indiana, United States, 46527
IU Health Central Indiana Cancer Centers
Indianapolis, Indiana, United States, 46219
Community Regional Cancer Center
Indianapolis, Indiana, United States, 46256
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Horizon Oncology Research
Lafayette, Indiana, United States, 47905
IU Health at Ball Memorial Hospital Cancer Center
Muncie, Indiana, United States, 47303
Monroe Medical Associates
Munster, Indiana, United States, 46321
Oncology Hematology Associates of SW Indiana
Newburgh, Indiana, United States, 47630
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
United States, Iowa
Siouxland Hematology Oncology Associates, LLP, Nylen Cancer Center
Sioux City, Iowa, United States, 51101
United States, Kansas
Cancer Center of Kansas
Wichita, Kansas, United States, 67214
United States, Kentucky
Kentucky Cancer Clinic
Hazard, Kentucky, United States, 41701
Purchase Cancer Group
Paducah, Kentucky, United States, 42001
United States, Louisiana
Medical Oncology LLC
Baton Rouge, Louisiana, United States, 70809
Metairie Oncologists
Metairie, Louisiana, United States, 70006
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
St. Joseph Mercy Hospital
Ann Arbor, Michigan, United States, 48106
Cancer and Hematology Centers of Western Michigan
Grand Rapids, Michigan, United States, 49546
Metro Health Cancer Care
Wyoming, Michigan, United States, 49519
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Montana
Bozeman Deaconness Cancer Center
Bozeman, Montana, United States, 59715
Sletten Cancer Specialists
Great Falls, Montana, United States, 59405
United States, Nebraska
Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Manchester, New Hampshire, United States, 03102
United States, New Jersey
Trinitas Regional Medical Center
Elizabeth, New Jersey, United States, 07202
Somerset Hematology Oncology Associates
Somerville, New Jersey, United States, 08876
United States, New Mexico
University of New Mexico Cancer Center: Albuquerque
Albuquerque, New Mexico, United States, 87131
Presbyterian Medical Group
Albuquerque, New Mexico, United States, 87110
United States, New York
New York Oncology Hematology, PC
Albany, New York, United States, 12208
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
NYU Langone Arena Oncology
Lake Success, New York, United States, 11042
Tisch Cancer Institute at Mount Sinai Medical Center
New York, New York, United States, 10029
Hematology Oncology Associates of Rockland
Nyack, New York, United States, 10960
United States, North Carolina
First Health of the Carolinas
Pinehurst, North Carolina, United States, 28374
United States, Ohio
Signal Point Clinical Research Center
Middletown, Ohio, United States, 45042
Lawrence M. Stallings, M.D.
Wooster, Ohio, United States, 44691
United States, Oklahoma
Mercy Physicians Of Oklahoma
Oklahoma City, Oklahoma, United States, 73120
United States, Oregon
Willamette Valley Cancer Institute
Springfield, Oregon, United States, 97477
United States, Pennsylvania
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822
Gettysburg Cancer Center
Gettysburg, Pennsylvania, United States, 17235
Allegheny Cancer Center
Pittsburgh, Pennsylvania, United States, 15212
Mount Nittany Medical Center
State College, Pennsylvania, United States, 16803
Berks Hematology Oncology Associates
West Reading, Pennsylvania, United States, 19611
United States, Rhode Island
Hematology and Oncology Associates of Rhode Island
Cranston, Rhode Island, United States, 02920
United States, South Carolina
MUSC Hollings Cancer Center
Charleston, South Carolina, United States, 29425
South Carolina Cancer Specialists
Hilton Head, South Carolina, United States, 29926
United States, Tennessee
The Jones Clinic, PC
Germantown, Tennessee, United States, 38138
United States, Texas
Texas Oncology: Austin North
Austin, Texas, United States, 78758
Texas Oncology: Bedford
Bedford, Texas, United States, 76022
Texas Oncology, PA
Dallas, Texas, United States, 75246
Texas Oncology: Fort Worth
Fort Worth, Texas, United States, 76104
Methodist Hospital Research Institute
Houston, Texas, United States, 77030
Houston Cancer Center
Houston, Texas, United States, 77055
Texas Oncology: Houston Memorial City
Houston, Texas, United States, 77024
Joe Arrington Cancer Research and Treatment Center
Lubbock, Texas, United States, 79410
CTRC at The UT Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
United States, Virginia
Lynchburg Hematology Oncology Clinic, Inc.
Lynchburg, Virginia, United States, 24501
United States, Washington
Harrison HealthPartners Bremerton Hematology & Oncology
Bremerton, Washington, United States, 98310
Cascade Cancer Center
Kirkland, Washington, United States, 98034
Group Health Medical Centers
Seattle, Washington, United States, 98109
University of Washington, Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Rockwood Clinic
Spokane, Washington, United States, 99204
United States, Wisconsin
University of Wisconsin, Clinical Cancer Center
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
Royal Prince Alfred Hospital: Sydney Cancer Centre
Camperdown, New South Wales, Australia, 2050
Prince of Wales Hospital
Randwick, New South Wales, Australia, 2031
Sydney Adventist Hospital Ltd.
Wahroonga, New South Wales, Australia, 2076
Australia, Queensland
Gallipoli Medical Research Foundation: Greenslopes Private Hospital
Greenslopes, Queensland, Australia, 4120
Royal Brisbane & Women's Hospital
Herston, Queensland, Australia, 4029
Princess Alexandra Hospital
Wolloongabba, Queensland, Australia, 4201
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Ashford Cancer Centre
Kurralta Park, South Australia, Australia, 5037
Australia, Tasmania
Gallipoli Medical Research Foundation: Launceston General Hospital
Launceston, Tasmania, Australia, 7250
Australia, Victoria
Peninsula Oncology Centre
Frankston, Victoria, Australia, 3199
Austin Hospital
Heidelberg, Victoria, Australia, 3084
Alfred Hospital
Melbourne, Victoria, Australia, 3004
Australia, Western Australia
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Singapore
National Cancer Centre Singapore
Singapore, Singapore, 169610
Sponsors and Collaborators
Hoosier Oncology Group
Bionomics Limited
Investigators
Study Chair: Thomas Hutson, D.O. Hoosier Oncology Group
  More Information

Additional Information:
No publications provided

Responsible Party: Hoosier Oncology Group
ClinicalTrials.gov Identifier: NCT01034631     History of Changes
Other Study ID Numbers: HOG GU09-145
Study First Received: December 15, 2009
Last Updated: September 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Hoosier Oncology Group:
Metastatic Kidney Cancer
BNC105P

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 17, 2014