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

21. Mai 2019 aktualisiert von: Anchiano Therapeutics Israel Ltd.

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

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

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

14

Phase

  • Phase 2
  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

      • Holon, Israel
        • The Edith Wolfson Medical Center
      • Jerusalem, Israel
        • Hadassah University Hospital
      • Kfar Saba, Israel
        • Meir Hospital
      • Tel Hashomer, Israel
        • Sheba Medical Center

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Weiblich

Beschreibung

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.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: N / A
  • Interventionsmodell: Einzelgruppenzuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 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.

Andere Namen:
  • DTA-H19

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Number of Participants With Dose-Limiting Toxicities
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Overall Survival in ITT Population
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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) - Maximum Observed Plasma Concentration (Cmax)
Zeitfenster: 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 - Tmax (Hours)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Ermittler

  • Hauptermittler: Tally Levy, M.D., The Edith Wolfson Medical Center
  • Hauptermittler: David Edelman, MD, Hadassah University Hospital
  • Hauptermittler: Ami Fishman, MD, Meir Medical Center
  • Hauptermittler: Eitan Rami, MD., Rabin Medical Center
  • Hauptermittler: Ofer Lavie, M.D., Carmel Medical Center
  • Hauptermittler: Ronnie Shapira-Frommer, MD, Sheba Medical Center

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. Juni 2009

Primärer Abschluss (Tatsächlich)

1. Februar 2012

Studienabschluss (Tatsächlich)

1. Februar 2012

Studienanmeldedaten

Zuerst eingereicht

18. Januar 2009

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

18. Januar 2009

Zuerst gepostet (Schätzen)

21. Januar 2009

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

13. Juni 2019

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

21. Mai 2019

Zuletzt verifiziert

1. Mai 2019

Mehr Informationen

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