Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Immune System Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Carboplatin

Antimetabolites

Phase II Arm A will randomize patients to treatment regimen of carboplatin and gemcitabine without BNC105P

Phase II Arm B will randomize patients to treatment regimen of carboplatin and gemcitabine and will include BNC105P

Carboplatin AUC4 on day 1 of 21-day cycle, for a maximum of 6 cycles.

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.

Carboplatin AUC 4 on day 1 of a 21 day cycle, for a maximum of 6 cycles.

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.

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.

BNC105P

Danny Rischin, Professor

Daniela Matei, M.D.

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.

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.

BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients

Phase I/II BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients in First or Second Relapse

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)

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)

To determine the progression free and overall survival distribution rates in this patient population

To determine the adverse event rates (Numbers (%) with G2-5 AE (NCI CTCAE v4.0)

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)

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients	NCT01624493	Ovarian Cancer	Carboplatin Gemcitabine Carboplatin Gemcitabine BNC105P	18 Years -	Hoosier Cancer Research Network
BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients	NCT01624493	Ovarian Cancer	Carboplatin Gemcitabine Carboplatin Gemcitabine BNC105P	18 Years -	Hoosier Cancer Research Network

Spots Global Cancer Trial Database for vascular disrupting agents