Clinical Trials /

PTC-596 in Women With Ovarian Cancer Receiving Neoadjuvant Chemotherapy

NCT03206645

Description:

This is an open-label Phase Ib dose-escalation study to determine the safety, tolerability, and pharmacokinetics of PTC-596 when combined with and following conventional chemotherapy and as maintenance therapy as a capsule (weight based dosing) and a tablet (fixed dosing) in women with epithelial ovarian, fallopian tube or primary peritoneal cancer which is previously untreated.

Related Conditions:
  • Fallopian Tube Adenocarcinoma
  • Fallopian Tube Undifferentiated Carcinoma
  • Malignant Ovarian Mixed Epithelial Tumor
  • Ovarian Adenocarcinoma
  • Ovarian Clear Cell Adenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Primary Peritoneal Clear Cell Carcinoma
  • Primary Peritoneal Endometrioid Adenocarcinoma
  • Primary Peritoneal Serous Adenocarcinoma
  • Primary Peritoneal Undifferentiated Carcinoma
  • Undifferentiated Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PTC-596 in Women With Ovarian Cancer Receiving Neoadjuvant Chemotherapy
  • Official Title: Phase 1B Trial With PTC-596 in High-Grade Serous Ovarian Cancer: a Targeted Approach Toward Chemoresistant Stem-Like Cancer Cells

Clinical Trial IDs

  • ORG STUDY ID: PTC-001
  • NCT ID: NCT03206645

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
PTC596Carboplatin/Paclitaxel + PTC596

Purpose

This is an open-label Phase Ib dose-escalation study to determine the safety, tolerability, and pharmacokinetics of PTC-596 when combined with and following conventional chemotherapy and as maintenance therapy as a capsule (weight based dosing) and a tablet (fixed dosing) in women with epithelial ovarian, fallopian tube or primary peritoneal cancer which is previously untreated.

Detailed Description

      For all cohorts, the study drug PTC-596 will be orally administered prior to chemotherapy
      (paclitaxel and carboplatin), twice a week of each 21-day cycle. Chemotherapy will be
      administered on day 1 of each cycle by vein. Dose escalation levels for PTC-596 will occur
      per protocol and doses may be de-escalated for management of toxicity. Patients will receive
      a total of 3 cycles of PTC-596 and chemotherapy. Surgery will be performed within 6 weeks
      after the last dose of Cycle 3. An additional 3-7 cycles of PTC-596 and chemotherapy
      (carboplatin and paclitaxel) may be given as maintenance therapy for up to two years at the
      discretion of the treating physician.
    

Trial Arms

NameTypeDescriptionInterventions
Carboplatin/Paclitaxel + PTC596ExperimentalCarboplatin AUC 6mg/L IV on day 1; Paclitaxel 175mg/m2 IV on day 1; PTC596 PO, twice a week, on day 1, 4, 8, 11, 15 and 18 per 21-day cycle for the first 3 cycles.
  • PTC596

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologic diagnosis of epithelial ovarian, fallopian tube, or
             primary peritoneal carcinoma per pre-treatment biopsies by laparoscopy, or
             interventional radiology or CT guided core biopsy.

          -  Patients with the following histologic epithelial cell types are eligible: High grade
             serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear
             cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise
             specified (N.O.S.).

          -  Adequate bone marrow function, renal function, hepatic function, and neurologic
             function per protocol.

          -  Patients should be free of active infection requiring parenteral antibiotics or a
             serious uncontrolled medical illness or disorder within four weeks of study entry.

          -  Any hormonal therapy directed at the malignant tumor must be discontinued at least one
             week prior to registration. Continuation of hormone replacement therapy is permitted.

          -  Patients must have a performance status score of 0, 1, or 2 by Eastern Cooperative
             Group (ECOG) criteria.

          -  Patients of childbearing potential must have a negative pregnancy test prior to the
             study entry and be practicing an effective form of contraception. If applicable,
             patients must discontinue breastfeeding prior to study entry.

          -  Patients must have satisfactory results for the baseline laboratory analyses and
             diagnostic procedures as specified in the protocol.

          -  Patients must have pre-treatment tumor tissue available or agree for tissue collection
             from IR guided biopsy.

          -  Life expectancy of at least 3 months

        Exclusion Criteria:

          -  Prior treatment with PTC596 or standard of care drugs (cis- or carboplatin or
             paclitaxel.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to PTC596 or other agents used in this study.

          -  Have a clinical requirement for ongoing systemic immunosuppressive therapy such as
             chronic steroid use not related to chemotherapy administration.

          -  Receiving treatment for active autoimmune disease.

          -  History of other invasive malignancies, with the exception of non-melanoma skin cancer
             and other specific malignancies within the last three years.

          -  Prior radiotherapy to any portion of the abdominal cavity or pelvis.

          -  Prior chemotherapy for any abdominal or pelvic tumor.

          -  Known active hepatitis, ongoing systemic bacterial, fungal, or viral infection; known
             human immunodeficiency virus (HIV) infection or acquired-immunodeficiency syndrome
             (AIDS)-related illness.

          -  Have concurrent severe medical problems unrelated to the malignancy that would
             significantly limit full compliance with the study.

          -  Have childbearing potential but not practicing adequate contraception.

          -  History or active CNS disease.

          -  Concomitant therapy with any of the following: other non-study cytotoxic chemotherapy;
             other investigational therapies.

          -  Prior bone marrow/hematopoietic stem cell transplantation

          -  History of solid organ, bone marrow, or progenitor cell transplantation

          -  History of major surgical procedure within 28 days prior to start of study treatment

          -  Presence or history of moderate to severe pulmonary dysfunction.

          -  Use of an investigational drug within 4 weeks of dosing in the current study
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose and dose limiting toxicities
Time Frame:42 days
Safety Issue:
Description:To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of PTC596 in combination with and following conventional chemotherapy and as maintenance as a capsule (weight-based dosing) and a tablet (fixed dosing). Standard chemotherapy will be comprised of carboplatin and weekly paclitaxel. The DLTs will be based on adverse events that occur during administration of the first 2 cycles of combination PTC596 and chemotherapy (a cycle = 21 days).

Secondary Outcome Measures

Measure:Evaluate clinical response
Time Frame:3 years
Safety Issue:
Description:Evaluate clinical response by measuring serum CA-125. If CA-125 is initially above the upper normal limit, it must normalize for patients to be considered in complete clinical response.
Measure:Evaluate pharmacokinetic Area Under the Curve (AUC)
Time Frame:3 months
Safety Issue:
Description:To evaluate pharmacokinetic parameters of PTC596 in patients with stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer receiving neoadjuvant chemotherapy with carboplatin/paclitaxel
Measure:Evaluate pharmacokinetic Maximum Concentration observed (Cmax)
Time Frame:3 months
Safety Issue:
Description:To evaluate pharmacokinetic parameters of PTC596 in patients with stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer receiving neoadjuvant chemotherapy with carboplatin/paclitaxel
Measure:Evaluate pharmacokinetic Time of Maximum Concentration observed (Tmax)
Time Frame:3 months
Safety Issue:
Description:To evaluate pharmacokinetic parameters of PTC596 in patients with stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer receiving neoadjuvant chemotherapy with carboplatin/paclitaxel
Measure:Evaluate pharmacokinetic half life (t1/2)
Time Frame:3 months
Safety Issue:
Description:To evaluate pharmacokinetic parameters of PTC596 in patients with stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer receiving neoadjuvant chemotherapy with carboplatin/paclitaxel
Measure:Progression free survival
Time Frame:one year
Safety Issue:
Description:The duration of time (one year) that patients are alive and their cancer is progression-free.
Measure:Progression free survival
Time Frame:two years
Safety Issue:
Description:The duration of time (two years) that patients are alive and their cancer is progression-free.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Oklahoma

Last Updated

November 21, 2019