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Trial record 1 of 2 for:    BNC105P
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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 Cancer Research Network
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 Cancer Research Network:

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01034631

  Show 108 Study Locations
Sponsors and Collaborators
Hoosier Cancer Research Network
Bionomics Limited
Investigators
Study Chair: Thomas Hutson, D.O. Hoosier Cancer Research Network
  More Information

Additional Information:
No publications provided

Responsible Party: Hoosier Cancer Research Network
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 Cancer Research Network:
Metastatic Kidney Cancer
BNC105P

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

ClinicalTrials.gov processed this record on November 27, 2014