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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:
Secondary Objectives: Secondary objectives of this study are:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BC-819 | Experimental | BC-819 60, 120 and 240 mg IP administration |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BC-819 | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities | 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. | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival in ITT Population | Overall survival, defined as the time from the start of treatment until the subject died, was estimated by Kaplan Meier curves. | 17.5 months |
| Solid Tumor Response |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tally Levy, M.D. | The Edith Wolfson Medical Center | Principal Investigator |
| David Edelman, MD | Hadassah University Hospital | Principal Investigator |
| Ami Fishman, MD | Meir Medical Center | Principal Investigator |
| Eitan Rami, MD. | Rabin Medical Center | Principal Investigator |
| Ofer Lavie, M.D. | Carmel Medical Center | Principal Investigator |
| Ronnie Shapira-Frommer, MD | Sheba Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Edith Wolfson Medical Center | Holon | Israel | ||||
| Hadassah University Hospital |
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Clinical sites
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| ID | Title | Description |
|---|---|---|
| FG000 | BC-819 60 mg IP | 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. |
| FG001 | BC-819 120 mg IP | 120 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course. |
| FG002 | BC-819 240 mg IP | 240 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | BC-819 60 mp IP | 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. |
| BG001 | BC-819 120 mg IP |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Dose-Limiting Toxicities | 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. | 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). | Posted | Count of Participants | Participants | 8 weeks |
|
Adverse events were assessed over a 16 week period, starting with each participant's first treatment with IP.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BC-819 60 mg IP | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac disorder | Cardiac disorders | MedDRA | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| VP Clinical | BioCancell Ltd. | +97225486553 | monique.ben-am@biocancell.com |
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
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|
|
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.
| 6 weeks |
| Systemic BC-819 Pharmacokinetics (PK) by Treatment - T1/2 (Hours) | 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. | Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion |
| Systemic BC-819 Pharmacokinetics (PK) - Maximum Observed Plasma Concentration (Cmax) | 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. | Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion |
| Systemic BC-819 Pharmacokinetics (PK) by Treatment - Tmax (Hours) | 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. | Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion |
| Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUClast | 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. | Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion |
| Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUCinf | 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. | Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion |
| Overall Survival in PP | Overall survival, defined as the time from the start of treatment until the subject died, was estimated by Kaplan Meier curves. | 17.5 months |
| Jerusalem |
| Israel |
| Meir Hospital | Kfar Saba | Israel |
| Sheba Medical Center | Tel Litwinsky | Israel |
120 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.
| BG002 | BC-819 240 mg IP | 240 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | BC-819 120 mg IP | 120 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course. |
| OG002 | BC-819 240 mg IP | 240 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course. |
|
|
| Secondary | Overall Survival in ITT Population | Overall survival, defined as the time from the start of treatment until the subject died, was estimated by Kaplan Meier curves. | 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. | Posted | Median | Full Range | Months | 17.5 months |
|
|
|
| Secondary | Solid Tumor Response | 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. | 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). | Posted | Count of Participants | Participants | 6 weeks |
|
|
|
| Secondary | Systemic BC-819 Pharmacokinetics (PK) by Treatment - T1/2 (Hours) | 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. | 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. | Posted | Mean | Standard Deviation | hours | Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion |
|
|
|
| Secondary | Systemic BC-819 Pharmacokinetics (PK) - Maximum Observed Plasma Concentration (Cmax) | 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. | 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. | Posted | Mean | Standard Deviation | copies/μL | Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion |
|
|
|
| Secondary | Systemic BC-819 Pharmacokinetics (PK) by Treatment - Tmax (Hours) | 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. | 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. | Posted | Mean | Standard Deviation | hours | Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion |
|
|
|
| Secondary | Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUClast | 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. | 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. | Posted | Mean | Standard Deviation | copies*hr/μl | Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion |
|
|
|
| Secondary | Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUCinf | 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. | 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. | Posted | Mean | Standard Deviation | copies*hr/μl | Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion |
|
|
|
| Secondary | Overall Survival in PP | Overall survival, defined as the time from the start of treatment until the subject died, was estimated by Kaplan Meier curves. | 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). | Posted | Median | Full Range | months | 17.5 months |
|
|
|
| 3 |
| 8 |
| 6 |
| 8 |
| 8 |
| 8 |
| EG001 | BC-819 120 mg IP | 120 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course. | 0 | 3 | 1 | 3 | 3 | 3 |
| EG002 | BC-819 240 mg IP | 120 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course. | 0 | 3 | 0 | 3 | 3 | 3 |
| Vomiting | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
|
| Elevated liver enzymes | Investigations | MedDRA | Non-systematic Assessment |
|
| Clinical deterioration | General disorders | MedDRA | Non-systematic Assessment |
|
| Recurrent urinary tract infection | Renal and urinary disorders | MedDRA | Non-systematic Assessment |
|
| Weakness and shortness of breath | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
|
| Infection of port | Infections and infestations | MedDRA | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
|
| Chest pain and dyspnea | Cardiac disorders | MedDRA | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
|
| Pulmonary embolism | Vascular disorders | MedDRA | Non-systematic Assessment |
|
| Gastrointestinal disorders | Gastrointestinal disorders | MedDRA | Non-systematic Assessment | All other Gastrointestinal disorders excluding constipation, diarrhea, Dyspepsia, and vomiting. |
|
| General disorders and administration site conditions | General disorders | MedDRA | Non-systematic Assessment | All other general disorders and administration site conditions excluding Asthenia and general physical health deterioration. |
|
| Infections | Infections and infestations | MedDRA | Non-systematic Assessment |
|
| Injury, poisoning and procedural complications | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment | All other Injury, poisoning and procedural complications excluding fall |
|
| Investigations | Investigations | MedDRA | Non-systematic Assessment | All other investigations excluding those listed in this table. |
|
| Hypocalcemia | Metabolism and nutrition disorders | MedDRA | Non-systematic Assessment |
|
| Hedache | Nervous system disorders | MedDRA | Non-systematic Assessment |
|
| Renal and urinary disorders | Renal and urinary disorders | MedDRA | Non-systematic Assessment | All other renal and urinary disorders excluding urinary tract infection. |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA | Non-systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
|
| Urinary tract infection | Renal and urinary disorders | MedDRA | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA | Non-systematic Assessment |
|
| Vascular disorders | Vascular disorders | MedDRA | Non-systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA | Non-systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA | Non-systematic Assessment |
|
| Blood calcium decreased | Investigations | MedDRA | Non-systematic Assessment |
|
| Blood potassium increased | Investigations | MedDRA | Non-systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA | Non-systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA | Non-systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA | Non-systematic Assessment |
|
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| D000291 |
| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| Title | Measurements |
|---|---|
|
| Not evaluable |
|