Clinical trial NCT00826150: Phase 1/2a Study of DTA-H19 in Advanced Stage Ovarian Cancer
Official title: Phase 1/2a, Dose-Escalation, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Intraperitoneal Administration of DTA-H19 in Subjects With Advanced Stage Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Keywords: ovarian cancer
H19 gene
plasmid
inodiftagene vixteplasmid
Lead sponsor: Anchiano Therapeutics Israel Ltd.
Sponsor class: INDUSTRY
First posted: 2009-01-21
Enrollment: 14
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Provide written informed consent and be at least 18 years of age.
* Have histopathologically documented epithelial ovarian carcinoma or primary peritoneal carcinoma with evidence of ascites.
* Have either a) platinum-refractory disease (i.e. persistent disease following completion of platinum-based primary chemotherapy) and have failed at least primary platinum-based chemotherapy; or b) platinum-resistant recurrent disease and have failed at least one regimen of second line chemotherapy.
* Be able to tolerate placement of IP catheter.
* Be at least 2 weeks from last treatment to allow recovery from prior toxicity but in the judgment of the investigator with sufficient time to ensure that the effects of prior treatments will not confound safety evaluations.
* Have a Karnofsky performance status score of ≥ 70%.
* Not be of child-bearing potential.
* Have a life expectancy of ≥ 3 months.
* Have serum creatinine \< 2.0 mg/dL, total bilirubin less than the institution's 3x upper limit of normal (ULN); AST and ALT \<= 2.5 x ULN,total albumin ≥ 2.5 g/dL, PT, PTT, and PT/INR within normal limits, absolute neutrophil count (ANC) \> 1,500 x 103 cells/mL, platelets ≥ 100,000/mL, and hemoglobin ≥ 10 mg/dL.
* Have a biopsy specimen or an ascites fluid that is positive for H19 expression.
* Have screening procedures completed within 6-weeks before starting treatment.
* No significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina or congestive heart failure.
* - No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while on this protocol.

Exclusion Criteria:

* Have evidence of extra abdominal disease with the exception of isolated small nodules (e.g., liver or pulmonary nodules) that are not causing symptoms.
* Have known brain metastases.
* Have known HIV infection.
* Have known active viral or bacterial infections.
* Have presence of any psychological, familiar, sociological, or geographical condition potentially hampering compliance with the study protocol or follow up schedule.
* Have a medical condition contraindicated for laparotomy, laparoscopy, or surgery.
* Have significant bowel involvement denoted by persistent grade 3 vomiting (≥6 episodes in 24 hrs; IV fluids, or total parenteral nutrition (TPN) indicated ≥24 hrs) after removal of ascites, inability to tolerate oral diet or medications, requirement for total parenteral nutrition, or recent (past six weeks) episode of bowel obstruction.
* Have a history of coagulopathy.

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities
timeFrame: 8 weeks
Secondary outcomes:
measure: Overall Survival in ITT Population
timeFrame: 17.5 months
measure: Solid Tumor Response
timeFrame: 6 weeks
measure: Systemic BC-819 Pharmacokinetics (PK) by Treatment - T1/2 (Hours)
timeFrame: Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
measure: Systemic BC-819 Pharmacokinetics (PK) - Maximum Observed Plasma Concentration (Cmax)
timeFrame: Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
measure: Systemic BC-819 Pharmacokinetics (PK) by Treatment - Tmax (Hours)
timeFrame: Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
measure: Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUClast
timeFrame: Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
measure: Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUCinf
timeFrame: Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
measure: Overall Survival in PP
timeFrame: 17.5 months
Other outcomes:
Locations:
city: Holon
country: Israel
facility: The Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Kfar Saba
country: Israel
facility: Meir Hospital
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: The Edith Wolfson Medical Center
name: Tally Levy, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hadassah University Hospital
name: David Edelman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Meir Medical Center
name: Ami Fishman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rabin Medical Center
name: Eitan Rami, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Carmel Medical Center
name: Ofer Lavie, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Sheba Medical Center
name: Ronnie Shapira-Frommer, MD
role: PRINCIPAL_INVESTIGATOR
References: