- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00826150
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
Studieoversikt
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiesteder
-
-
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Holon, Israel
- The Edith Wolfson Medical Center
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Jerusalem, Israel
- Hadassah University Hospital
-
Kfar Saba, Israel
- Meir Hospital
-
Tel Hashomer, Israel
- Sheba Medical Center
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: BC-819
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.
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Number of Participants With Dose-Limiting Toxicities
Tidsramme: 8 weeks
|
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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Overall Survival in ITT Population
Tidsramme: 17.5 months
|
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
Tidsramme: 6 weeks
|
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)
Tidsramme: Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
|
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
|
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Systemic BC-819 Pharmacokinetics (PK) - Maximum Observed Plasma Concentration (Cmax)
Tidsramme: Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
|
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
|
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Systemic BC-819 Pharmacokinetics (PK) by Treatment - Tmax (Hours)
Tidsramme: Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
|
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
Tidsramme: Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
|
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
Tidsramme: Before the start of the infusion of BC-819 and 2, 4, 6, 8, 24, and 48 hours after the start of the infusion
|
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
Tidsramme: 17.5 months
|
Overall survival, defined as the time from the start of treatment until the subject died, was estimated by Kaplan Meier curves.
|
17.5 months
|
Samarbeidspartnere og etterforskere
Etterforskere
- Hovedetterforsker: Tally Levy, M.D., The Edith Wolfson Medical Center
- Hovedetterforsker: David Edelman, MD, Hadassah University Hospital
- Hovedetterforsker: Ami Fishman, MD, Meir Medical Center
- Hovedetterforsker: Eitan Rami, MD., Rabin Medical Center
- Hovedetterforsker: Ofer Lavie, M.D., Carmel Medical Center
- Hovedetterforsker: Ronnie Shapira-Frommer, MD, Sheba Medical Center
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Neoplasmer etter histologisk type
- Neoplasmer
- Urogenitale neoplasmer
- Neoplasmer etter nettsted
- Karsinom
- Neoplasmer, kjertel og epitel
- Genitale neoplasmer, kvinnelige
- Sykdommer i det endokrine systemet
- Sykdommer i eggstokkene
- Adnexal sykdommer
- Gonadal lidelser
- Neoplasmer i endokrine kjertel
- Neoplasmer i eggstokkene
- Karsinom, ovarieepitel
Andre studie-ID-numre
- BC-08-01
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