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.

To determine the associations between baseline biomarkers, ORR, PFS, OS and AE

University of Sydney

Australia New Zealand Gynaecological Oncology Group

Bionomics Limited

Hoosier Cancer Research Network

Blood and Lymph Conditions

Symptoms and General Pathology

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Amino Acids

Ibrutinib

Tubulin Modulators

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Evaluate the MTD of BNC105P in combination with ibrutinib in patients with relapsed/refractory CLL. Treatment will be administered on an outpatient basis but will also be permitted inpatient. BNC105P will be administered as a single agent prior to initiation of ibrutinib. Beginning with cycle 2, ibrutinib will be administered concomitantly with BNC105P at a starting dose of 420 mg PO daily. Each cycle will last for 21 days. Provided no toxicities occur, each patient will be treated for 6 cycles.

BNC105P is the phosphate ester of BNC105, a small molecule tubulin polymerization inhibitor.

Lionel D Lewis, MD

A Phase I Trial of BNC105P in combination with BTK inhibitor ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia(CLL). This study proposes that ibrutinib will have far greater efficacy when it is combined with drugs that kill the CLL cells in peripheral circulation, thereby preventing them from returning to the protective lymph node niche. The study will establish the maximum tolerated dose(MTD) of the combination of BNC105P with ibrutinib, characterize the pharmacodynamic effects of BNC105P alone and in combination with ibrutinib in CLL cells, and provide preliminary assessment of the efficacy of the combination in CLL.

The study consists of a Screening Period with baseline tumor assessment before BNC105P administration, a Treatment Period with up to six 21-day cycles and Follow-up Period. Subjects will receive a total of six cycles of therapy unless treatment is discontinued

A Phase I Trial of BNC105P in combination with BTK inhibitor ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Ibrutinib inhibits the pro-survival BCR signaling of CLL cells in the stromal niche resulting in their egress to the periphery. Importantly, if administration of ibrutinib is stopped, the CLL cells rapidly return to the lymph node. In some patients, the drug-induced increase in circulating CLL cells has been seen for more than a year reflecting the fact that the cells do not readily die once they exit the lymph node. Resistance to ibrutinib has been observed as mutations in the drug-binding cysteine in its target, BTK. This resistance is likely to become far more prevalent as patients remain on ibrutinib for months or years. We propose that ibrutinib will have far greater efficacy when it is combined with drugs that kill the CLL cells in peripheral circulation, thereby preventing them from returning to the protective lymph node niche. BNC105P works through an entirely different mechanism, i.e. tipping the balance of pro-survival and pro-apoptotic BCL2 family member proteins toward the latter, resulting in cell death. This pathway of apoptosis occurs at all stages of the cell cycle which is important considering that the majority of peripheral CLL cells are non-cycling (in G0).

The study consists of a Screening Period with baseline tumor assessment before BNC105P administration, a Treatment Period with up to six 21-day cycles and Follow-up Period. Subjects will receive a total of six cycles of therapy unless treatment is discontinued.

Open label dose escalation study, with a Storer D ; 3-3 cohort design

A Study of BNC105P Combined With Ibrutinib

A Phase 1 Trial of BNC105P & Ibrutinib in Patients w/ Relapsed/Refractory CLL

Study the effects of BNC105P as monotherapy and when used in combination with ibrutinib on the activation of NOXA and JNK in chronic lymphocytic leukemia cells using Western blots.

The number of relapsed refractory chronic lymphatic leukemia patients, in cohorts of 3-6, who develop treatment related adverse effects from combined therapy with BNC105P and ibrutinib. The treatment related adverse events will be defined based on CTCAE v 4.0

The number of relapsed refractory CLL patients in each dosing cohort (n= 3-6 patients) who when treated with BNC105P combined with ibrutinib will have therapeutic benefit based on CLL response criteria using CT imaging

Overall response rate (ORR) will be determined based on the number of study participants who achieve CR, CRi, PR or nPR assessed two months after completion of therapy, as per IWCLL 2008 criteria.

The timeframe is consistent with the Measure Title

Event-free survival (EFS), defined as the interval between the date of first study treatment and the date of objective signs of disease recurrence, subsequent anti-leukemic therapy, or death, whichever is first reported.

Dartmouth-Hitchcock Medical Center

Professor of Medicine, Pharmacology/Toxicolgy

Carcinoma, Renal Cell

Kidney Neoplasms

Adenocarcinoma

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Immunosuppressive Agents

Immunologic Factors

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.

Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals

Thomas Hutson, D.O.

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.

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.

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

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

Determine the toxicities of BNC105P in combination with everolimus. Drug-related treatment emergent adverse events by CTCAE grade 2 or greater are reported

Improvement in 6-month PFS with the addition of BNC105P to everolimus. Progression is defined using RECIST criteria as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

Number of objective responses per RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Determine the PK Profile for BN105P in combination with everolimus by calculating the geometric mean half-life of BNC105P

Objective response is defined as a confirmed CR or PR per RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Median time to progression for arm P participants who crossed over to BNC105P monotherapy after progression. Progression is defined per RECIST criteria as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

Determine adverse events of everolimus and BNC105P when administered as a combination or sequential regimen. Total number of serious and non-serious adverse events for Arm A and Arm B are summarized. Complete adverse event information is supplied in the Adverse Events reporting section.

Determine overall survival probability, up to a maximum of 5 years from registration for protocol therapy.

Exploratory analysis of serum biomarkers were undertaken to generate a potential signature for response. The correlation with 6 month progression free survival P value for four plasma biomarkers is reported.

Participants in the phase I dose escalation portion of the study.

Phase I Participants

Phase II: Arm A

Phase II: Arm B Participants

Phase II Participants, Arm A

Everolimus + BNC105P

Phase II: Arm B Participants

Everolimus only, followed by BNC105P monotherapy

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Karnofsky Performance Status (KPS) is a general indicator of a subject's well being and ability to carry on daily activities. The KPS scale ranges from 0-100 in 10 unit increments where 100=Normal; no complaints; no evidence of disease and 0=Dead

Initial Karnovksy Performance Score (KPS)

MSKCC Risk Group - Good

MSKCC Risk Group - Intermediate

MSKCC Risk Group - Poor

Memorial Sloan Kettering Cancer Center Risk Group (MSKCC

Lung

Liver

Bone

Brain

Metastatic Site

1 Prior Therapy

2 Prior Therapies

3 Prior Therapies

>=4 Prior Therapies

Number of Prior Therapies

Clinical Data Coordinator

15 total Participants were recruited to the phase I portion of the study.

12 participants completed at least one cycle of combination therapy and were evaluable.

Phase I: Maximum Tolerated Dose of BNC105P in Combination With Everolimus.

AST-SGOT Grade 2

Cough Grade 2

Dyspepsia Grade 2

Hemoglobin Grade 2

Hemoglobin Grade 3

Hypomagnesia Grade 2

Low Platelets Grade 2

Weight Loss Grade 2

Fatigue Grade 2

Left ventricular systolic dysfunction Grade 2

Mucositis (oral) Grade 2

Nail Infection Grade 2

Diaphoresis Grade 2

Pericardial effusion Grade 3

Pleural effusion Grade 2

12 participants who completed at least one cycle of combination therapy.

Phase I: Toxicities of BNC105P in Combination With Everolimus.

Combination Arm A: Everolimus 10 mg, BNC105P MTD (from Phase 1 study) 21 day cycle

Everolimus: Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals

BNC105P: BNC105P, up to 16 mg/m\^2

Combination Arm A: Everolimus + BNC105P

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.

Everolimus: Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals

BNC105P: BNC105P, up to 16 mg/m\^2

Sequential Arm B:Everolimus Followed by BNC105P Monotherapy

Phase II: 6-month Progression Free Survival (PFS) With the Addition of BNC105P to Everolimus.

Unknown

Phase I: Response Rate of BNC105P in Combination With Everolimus.

Half-life of BNC105

Half-life of BNC105P

14 participants has sufficient data collected for the analysis of this objective

Geometric Mean Half-life of BNC105 and BNC105P in Combination With Everolimus.

Phase II: Response Rate With Combination Therapy Compared to Everolimus Alone

After progression on everolimus, 33 participants crossed over to BNC105P monotherapy per protocol.

Arm B Participants Who Crossed Over to BNC105P Monotherapy

Phase II: Progression Free Survival (PFS) With BNC105P Alone in Patients After Progressing on Everolimus.

Non-Serious Adverse Events

Serious Adverse Events

Phase II: Adverse Events of Everolimus and BNC105P When Administered as a Combination or Sequential Regimen.

Phase II: Overall Survival

Serum Amyloid P-Component (SAP)

Sex Hormone-Binding Globulin (SHBG)

Matrix Metalloproteinase-9 (MMP-9)

Stem Cell Factor (SCF)

A subset of Phase II Participants who had sufficient correlative samples drawn for plasma biomarker analysis.

Phase II Participants With Sufficient Correlative Samples

Analysis was pre-specified to look at the correlation irrespective of arm.

Exploratory Objective: Correlation of PFS With Biomarkers

Phase II Participants, Arm A

Everolimus 10mg + BNC105P(Phase I MTD)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients	NCT01624493	Ovarian Cancer	Carboplatin Gemcitabine Carboplatin Gemcitabine BNC105P	18 Years -	Hoosier Cancer Research Network
A Study of BNC105P Combined With Ibrutinib	NCT03454165	Chronic Lymphoc...	BNC105P Ibrutinib	18 Years -	Dartmouth-Hitchcock Medical Center
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 in Combination With Everolimus/Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma	NCT01034631	Renal Cell Carc...	Everolimus BNC105P	18 Years -	Hoosier Cancer Research Network

Spots Global Cancer Trial Database for bnc105p

Every month we try and update this database with for bnc105p cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bnc105p

Every month we try and update this database with for bnc105p cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bnc105p cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.