BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients

This study has been completed.
University of Sydney
Australia New Zealand Gynaecological Oncology Group
Bionomics Limited
Information provided by (Responsible Party):
Hoosier Cancer Research Network Identifier:
First received: June 15, 2012
Last updated: April 17, 2015
Last verified: April 2015
This phase I/II trial will determine the recommended dose and activity of BNC105P for patients with partially platinum sensitive ovarian cancer in first or second relapse.

Condition Intervention Phase
Ovarian Cancer
Drug: Carboplatin
Drug: Gemcitabine
Drug: BNC105P
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients in First or Second Relapse

Resource links provided by NLM:

Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • Phase I: Determine Maximum Tolerated Dose for Patients [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To determine the recommended dose of BNC105P given with gemcitabine and carboplatin (maximum dose of BNC105P with no more than 1 DLT in 6 phase I participants)

  • Phase II: Determine Objective Response Rate in Patients [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To determine the objective response rate (ORR) in those with evaluable disease (ORR = CR, PR according to RECIST 1.1 and/or GCIG CA125 criteria) (percentage of those with measurable disease achieving CR or PR according to RECIST 1.1 and/or GCIG CA125 criteria)

Secondary Outcome Measures:
  • Progression Free and Overall Survival Distribution [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To determine the progression free and overall survival distribution rates in this patient population

  • Patient Side Effects and Tolerability [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To determine the adverse event rates (Numbers (%) with G2-5 AE (NCI CTCAE v4.0)

  • Patient Quality of Life Benefits [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To determine the effects on aspects of health related quality of life (HRQL measured with FOSI and MOST), including symptom benefit (Numbers (%) with significant symptom benefit)

  • Assessment of BNC105P Pharmacokinetics to Determine Interaction with Carboplatin and Gemcitabine [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Plasma will be collected to assess BNC105P pharmacokinetics on days 2 and 9 of cycle 1 only. Results will be compared with data from previous trials of BNC105P to determine their consistency and to establish if there is any major interaction with carboplatin and gemcitabine.

  • Association of Biomarkers, Predictions and Outcomes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To determine the associations between baseline biomarkers, ORR, PFS, OS and AE

Estimated Enrollment: 134
Study Start Date: October 2012
Study Completion Date: October 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase II Arm A
Phase II Arm A will randomize patients to treatment regimen of carboplatin and gemcitabine without BNC105P
Drug: Carboplatin
Carboplatin AUC4 on day 1 of 21-day cycle, for a maximum of 6 cycles.
Drug: Gemcitabine
Gemcitabine escalations 800 and 1000 mg/m2 (as determined in phase I) on days 1 and 8 of a 21 day cycle, for a maximum of 6 cycles.
Experimental: Phase II Arm B
Phase II Arm B will randomize patients to treatment regimen of carboplatin and gemcitabine and will include BNC105P
Drug: Carboplatin
Carboplatin AUC 4 on day 1 of a 21 day cycle, for a maximum of 6 cycles.
Drug: Gemcitabine
Gemcitabine 800 or 1000 mg/m2 (as determined in phase I) on days 1 and day 8 of 21-day cycle, for a maximum of 6 cycles.
Drug: BNC105P
BNC105P as determined in phase I, on days 2 and 9 of a 21 day cycle for a maximum of 6 cycles, followed by single agent maintenance BNC105P 16 mg/m2 for a maximum of 6 additional cycles.

  Show Detailed Description


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria for Phase I Only:

  • Histologically or cytologically proven diagnosis of epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer, including all histological subtypes and carcinosarcoma.

Inclusion Criteria for Phase II Only:

  • Histologically proven diagnosis of epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer.
  • Progression-free interval between 4 to 9 months after first line chemotherapy or 4 to 12 months after second-line chemotherapy with a platinum (cisplatin or carboplatin) based regimen.
  • Subjects must have progressed (based on GCIG CA125 and/or RECIST criteria) after last platinum based regimen.
  • Subjects must be assessable for response based on GCIG CA125 and/or RECIST criteria.
  • Subjects with clinically evident ascites and/or pleural effusions must be assessable by RECIST.
  • Study treatment both planned and able to start within 7 days of randomisation

Exclusion Criteria for Phases I and II:

  • Non-epithelial ovarian cancer and ovarian tumours of low malignant potential (borderline tumours)
  • More than two prior chemotherapy regimens for ovarian cancer (excluding hormonal therapy or biologic agents).
  • Any prior chemotherapy for other cancers, but >10 years permitted for phase II only, except for high dose chemotherapy/autologous or allogeneic transplantation
  • Chemotherapy within 20 days prior to registration.
  • Hormonal therapy or biologic therapy within 28 days prior to registration
  • Concurrent treatment with any experimental drugs or other anti-cancer therapy.
  • Concurrent treatment with clopidogrel, ticlopidine, persantin and other antiplatelet agents
  • Radiotherapy within 21 days prior to registration, or to greater than 15% of the bone marrow.
  • Persistent toxic effects of previous chemotherapy of greater than Grade 1 severity (CTCAE v 4, appendix 8)
  • Known brain or leptomeningeal disease (baseline CT brain or MRI is only required if there is clinical suspicion of central nervous system involvement).
  • Subjects with other invasive malignancies who had (or have) any evidence of another cancer present within the last 3 years, with the exception of early stage non-melanoma skin cancer, carcinoma in situ of cervix, and synchronous endometrial cancer (stage 1 G1,2)
  • Untreated and/or uncontrolled cardiovascular conditions and/or symptomatic cardiac dysfunction (unstable angina, congestive cardiac failure, myocardial infarction) within the previous year, or cardiac ventricular arrhythmias requiring medication, or history of 2nd or 3rd degree atrioventricular conduction defects.
  • Cerebrovascular accident or transient ischemic attack within 6 months prior to registration.
  • Poorly controlled hypertension: systolic BP >150 or diastolic BP >100 mmHg. Antihypertensive medications are permitted but BP must be ≤150 systolic and ≤100 diastolic on 2 readings separated by at least 24 hours.
  • Deep vein thrombosis, pulmonary embolism, within 6 months of registration or arterial thrombosis, or arterial embolism within 12 months prior to registration.
  • Receiving full dose, therapeutic anti-coagulation with warfarin, related oral anti-coagulants or unfractionated or low molecular weight heparin. Low dose heparin given for prophylaxis, and aspirin at a dose ≤ 325 mg/day is acceptable.
  • Significant infection including active hepatitis B, hepatitis C with abnormal liver function tests, or HIV. Testing for these is not mandatory. Screening for Hepatitis B should be as per institutional policy. Patients known to be Hep B surface antigen positive will be not be eligible even if on antiviral treatment.
  • Serious medical or psychiatric conditions which might prevent management according to the protocol.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomisation
  • Pregnancy, lactation, or inadequate contraception. Women must be post menopausal or sterile, or use two reliable means of contraception. Women of childbearing potential must have a pregnancy test taken and proven negative within 7 days prior to registration.
  • Life expectancy of less than 12 weeks.

Exclusion Criteria for Phase II only:

  • Carcinosarcoma and mucinous carcinoma
  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 identifier: NCT01624493

United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Australia, New South Wales
Royal Prince Alfred Hospital
Sydney, New South Wales, Australia, 2050
Australia, Queensland
Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia, 4029
Australia, Victoria
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia, 8006
New Zealand
Christchurch Hospital
Christchurch, Canterbury, New Zealand, 4710
Sponsors and Collaborators
Hoosier Cancer Research Network
University of Sydney
Australia New Zealand Gynaecological Oncology Group
Bionomics Limited
Study Chair: Danny Rischin, Professor University of Sydney
Principal Investigator: Daniela Matei, M.D. Hoosier Cancer Research Network
  More Information

Additional Information:
Danny Rischin, Daniela Matei, Jeffrey C. Goh, Michelle Margaret Vaughan, Philip James Beale, Meaghan Elizabeth Tenney, Julie Martyn, Dirkje Willemien Sommeijer, Jose Luis Iglesias, David C. Bibby, Jeremy Simpson, Elizabeth E. Doolin, Corinne E. Williams, Martin R. Stockler. A phase I/II study of the vascular disrupting agent BNC105P in combination with gemcitabine-carboplatin in partially platinum-sensitive ovarian cancer patients in first or second relapse: An international collaborative group trial of ANZGOG and HOG. J Clin Oncol 31, 2013 (suppl; abstr TPS5612)

Responsible Party: Hoosier Cancer Research Network Identifier: NCT01624493     History of Changes
Other Study ID Numbers: GYN12-154 / ANZGOG-1103
Study First Received: June 15, 2012
Last Updated: April 17, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Hoosier Cancer Research Network:
Vascular Disrupting Agents
Partially platinum sensitive

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses processed this record on November 25, 2015