Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

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

BC-819 60, 120 and 240 mg IP administration

Cohort #1: 60 mg IP weekly for 3 weeks, one week rest, then repeat for 2 more courses / 60 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

Cohort #2: 120 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

Cohort #3: 240 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

BC-819

Tally Levy, M.D.

David Edelman, MD

Ami Fishman, MD

Eitan Rami, MD.

Ofer Lavie, M.D.

Ronnie Shapira-Frommer, MD

This study is designed to assess the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of DTA-H19 administered intraperitoneally (IP) in subjects with advanced stage ovarian cancer, or primary peritoneal carcinoma

This is a Phase 1/2a, open label, dose escalation, repeat dose study in 11 subjects with recurrent, platinum resistant advanced stage ovarian cancer or primary peritoneal carcinoma designed to determine the tolerability, safety, quality of life, PK, and preliminary efficacy of DTA-H19 administered intraperitoneally(IP).

Primary Objective: The primary objectives of this study are:

* To determine the maximum tolerated dose (MTD) of IP DTA-H19; and,
* To identify any dose limiting toxicities (DLTs).

Secondary Objectives: Secondary objectives of this study are:

* To determine quality of life of subjects with advanced ovarian cancer, primary peritoneal carcinoma treated with IP DTA-H19;
* To determine the the reduction in malignant ascites as measured by Ultrasound and change in frequency of parecenteses necessary.
* To determine the overall survival distribution.

Phase 1/2a Study of DTA-H19 in Advanced Stage Ovarian Cancer

Phase 1/2a, Dose-Escalation, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Intraperitoneal Administration of DTA-H19 in Subjects With Advanced Stage Ovarian Cancer

A dose limiting toxicity (DLT) was defined as any grade 3 or greater non-hematologic AE by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). If one subject in a cohort experienced a DLT, then three additional subjects had to be enrolled to that cohort unless a second subject in that cohort experiences a DLT. The next lower dose was to be considered the MTD.

Overall survival, defined as the time from the start of treatment until the subject died, was estimated by Kaplan Meier curves.

If measurable disease was present, then the response of each marker lesion was evaluated separately and rated for response according to RECIST criteria for solid tumors.

Complete Response: Disappearance of the target lesion. Partial Response: At least a 30% decrease in the longest diameter of the target lesion.

Stable Disease: No sufficient shrinkage to qualify for partial response, or sufficient increase to qualify for progressive disease.

Progressive Disease: At least a 20% increase in the longest diameter of the target lesion.

Blood was collected at the indicated time points, then analyzed with a quantitative polymerase chain reaction (Q-PCR) method to quantitate the amount of plasmid present.

Anchiano Therapeutics Israel Ltd.

60 mg IP weekly for 3 weeks, one week rest, then repeat for 2 more courses / 60 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

BC-819 60 mg IP

120 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

BC-819 120 mg IP

BC-819 240 mg IP

BC-819 60 mp IP

240 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Israel

Region of Enrollment

VP Clinical

Per Protocol data set (PP): 11 subjects who met the study inclusion and exclusion criteria, received at least one course of treatment of the investigational product and had a follow-up disease assessment comprised the PP set (5 subjects from the 60 mg cohort, 3 subjects from the 120 mg cohort; 3 subjects from the 240 mg cohort).

Number of Participants With Dose-Limiting Toxicities

Intent to Treat (ITT) data set: subjects who participated in the study were included in the safety and in the ITT analysis. All 14 subjects who participated in the study were included in the ITT.

Overall Survival in ITT Population

Stable Disease

Progressive Disease

Not evaluable

Intent To Treat (ITT) data set: subjects who participated in the study were included in the safety and in the ITT analysis. All 14 subjects who participated in the study were included in the ITT. 13 patients of the ITT population (n=14) were evaluated (one patient was not assessed for solid tumor response in the BC-819 60 mg IP Arm).

Solid Tumor Response

Intent To Treat (ITT) data set: subjects who participated in the study were included in the safety and in the ITT analysis. All 14 subjects who participated in the study were included in the ITT.

Systemic BC-819 Pharmacokinetics (PK) by Treatment - T1/2 (Hours)

60 mg IP weekly for 3 weeks, one week rest, then repeat for 2 more courses/ 60 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

Systemic BC-819 Pharmacokinetics (PK) - Maximum Observed Plasma Concentration (Cmax)

Systemic BC-819 Pharmacokinetics (PK) by Treatment - Tmax (Hours)

Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUClast

Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUCinf

Overall Survival in PP

Overall Study

Infections

Carcinoma, Transitional Cell

Urinary Bladder Neoplasms

Diphtheria

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Transitional Cell Carcinoma

DTA-H19

Abraham Sidi, MD

Ilan Leibovitch, MD

This study is designed to assess the safety and preliminary efficacy of five different doses of DTA-H19 given as six intravesical infusions into the bladder of patients with superficial bladder cancer who have failed intravesical therapy with Bacille Calmette-Guérin (BCG).DTA-H19 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin \[diphtheria toxin A (DTA) chain\]only in cancer cells and not in normal cells. In line with the standard procedure for DNA plasmid pharmaceutical products, another chemical component will be added to the solution, called PEI (polyethlenimine) in a liquid solution, which improves the ability of the DNA plasmid to enter the cells.

This study is designed to assess the safety and preliminary efficacy of five different doses of DTA-H19 given as six intravesical infusions into the bladder of patients with superficial bladder cancer \[stages Ta and carcinoma in situ (CIS)\] who have failed intravesical therapy with Bacille Calmette-Guérin (BCG). The primary safety outcome measure is the maximum tolerated dose (MTD). DTA-H19 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin \[diphtheria toxin A (DTA) chain\]. This is a Patient-Oriented, Targeted Therapy as DTA expression is triggered by the presence of H19 transcription factors found only in bladder tumor and not normal bladder cells.

A maximum of 18 patients with histologically confirmed H19 positive superficial bladder cancer with multiple or recurrent stage Ta tumors or CIS will be included in this study. Patients with any grade 3, or any stage T1 or higher stage, will be excluded. This is a multicenter, dose escalation study in which, after eligibility criteria have been met, patients in five groups of 3 patients each, will receive escalating doses of DTA-H19 intravesically over a seven-week period. Treatments will be given weekly for three weeks followed one week later by safety and disease assessments, then another 3 weekly instillations will be performed. Each dose cohort will receive the same dose for all treatments. The first dose cohort will receive 2 mg of DTA-H19 plasmid per intravesical treatment for all treatments. The next dose cohort of 3 patients will receive 4 mg, the next 6 mg, the next 12 mg,and then the final dose cohort will receive 20 mg of DTA-H19 plasmid DNA. All doses will be mixed with polyethylenimine (PEI) to improve transduction efficiency. Doses will be escalated if none of the first three patients in the preceding dose cohort experience a dose limiting toxicity (DLT) after the first three weekly intravesical treatments.

Clinical responses will be assessed 4, 8, and 12 weeks after the start of treatment. If the stage Ta marker lesion is still present at the week 12 assessment, it will be resected by transurethral resection (TUR). Patients whose disease has not progressed (i.e., no new lesions, increase in the size of the marker lesion, by at least 50%, or increase in stage or any grade 3) will be offered continued once monthly treatments and follow-up for up to one year

Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer

Phase 1/2a, Dose-Escalation, Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer

Hebrew University of Jerusalem

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1/2a Study of DTA-H19 in Advanced Stage Ovarian Cancer	NCT00826150	Ovarian Cancer	BC-819	18 Years -	Anchiano Therapeutics Israel Ltd.
Phase 1/2a Study of DTA-H19 in Advanced Stage Ovarian Cancer	NCT00826150	Ovarian Cancer	BC-819	18 Years -	Anchiano Therapeutics Israel Ltd.
Safety and Proof of Concept Study of Intravesical DTA-H19 in Patients With Superficial Bladder Cancer	NCT00393809	Bladder Neoplas...	DTA-H19	18 Years -	Hebrew University of Jerusalem

Spots Global Cancer Trial Database for h19 gene

Every month we try and update this database with for h19 gene 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 h19 gene

Every month we try and update this database with for h19 gene 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 h19 gene 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.