Phase I/II BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients in First or Second Relapse
18 Years
N/A
Female
Ovarian Cancer
Trial Information
Phase I/II BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients in First or Second Relapse
OUTLINE: This is a multi-center study.
BNC105P is a novel vascular disrupting agent (VDA) with promising preclinical activity
combined with platinum or gemcitabine. The results of standard chemotherapy with carboplatin
and gemcitabine for ovarian cancer relapsing within 12 months of an initial platinum-based
regimen require improvement. This trial will determine the recommended dose and activity of
BNC105P administered with carboplatin and gemcitabine.
PHASE I:
This trial uses a standard 3+3 design for allocating participants to a starting dose level
in Phase I.
If dose level 1 is deemed to have acceptable toxicity then dose levels 2a and 2b can be
opened at the same time. Dose level 3 will only open if both dose levels 2a and 2b are
deemed to have acceptable toxicity.
The underlying assumptions for determining the recommended doses for the triple combination
of carboplatin, gemcitabine and BNC105P are that the likely minimum doses required of each
agent are carboplatin AUC 4, gemcitabine 800 mg/m2 and BNC105P 12 mg/m2. This corresponds to
dose level 1.
PHASE II 1:1 RANDOMIZATION:
Carboplatin AUC 4 on day 1, gemcitabine 800 or 1000 mg/m2 on days 1 and 8 of a 21 day cycle
for a maximum of 6 cycles.
OR
Carboplatin AUC 4 on day 1, gemcitabine 800 or 1000 mg/m2 on days 1 and day 8 with dose of
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
Minimum follow up for 12 months
ECOG Performance Status for Phase I: 0-1; ECOG Performance Status for Phase II: 0-2
Life Expectancy: Less than 12 weeks
Hematopoietic (both phases):
- Platelet count ≥ 100 x 109/L
- ANC ≥ 1.5 x 109/L
- Haemoglobin > 9g/dl (can be post transfusion)
- INR ≤ 1.5 x ULN
Hepatic (both phases):
- Total Bilirubin ≤ 1.5 x the upper limit of normal (ULN)
- ALT ≤ 2.5 x ULN
Renal (both phases):
- Creatinine clearance ≥ 55 mL/min according to Cockcroft Gault formula
- If Calculated GFR is 50 - 54 mL/min an isotopic GFR may be performed. If the isotopic
GFR is > 55ml/min, the patient will be eligible for the study but the calculated GFR
will be used for dose calculation.
Cardiovascular (both phases):
- Normal left ventricular ejection fraction (LVEF), i.e. ≥ 50% on Gated Heart Pool Scan,
or fractional shortening on echocardiogram ≥ institutional LLN performed within 2
months prior to randomisation
- Corrected QTc < 470 msec on ECG performed within 4 weeks prior to randomisation.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Phase I: Determine Maximum Tolerated Dose for Patients
Outcome Description:
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)
Outcome Time Frame:
12 months
Safety Issue:
Yes
Principal Investigator
Danny Rischin, Professor
Investigator Role:
Study Chair
Investigator Affiliation:
University of Sydney
Authority:
United States: Food and Drug Administration
Study ID:
GYN12-154 / ANZGOG-1103
NCT ID:
NCT01624493
Start Date:
October 2012
Completion Date:
October 2014
Related Keywords:
- Ovarian Cancer
- Vascular Disrupting Agents
- BNC105P
- Partially platinum sensitive
- Ovarian Neoplasms
Name | Location |
|---|---|
| Indiana University Melvin and Bren Simon Cancer Center | Indianapolis, Indiana 46202-5289 |
| University of Chicago | Chicago, Illinois 60637 |
