Clinical Trials /

p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246

NCT02098343

Description:

The purpose of this study is to make a preliminary assessment of the efficacy of a combined APR-246 and carboplatin/PLD chemotherapy regimen, compared with carboplatin/PLD chemotherapy regimen alone, in patients with platinum sensitive recurrent high grade serous ovarian cancer (HGSOC) with mutated p53. In addition, the study aims to assess the safety profile of the combined APR-246 and carboplatin/PLD chemotherapy regimen compared with carboplatin/PLD chemotherapy regimen alone, to evaluate potential biomarkers, and to assess the biological activity in tumor and surrogate tissues. The trial will enroll up to a maximum of 400 patients.

Related Conditions:
  • Ovarian Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246
  • Official Title: PiSARRO: p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246

Clinical Trial IDs

  • ORG STUDY ID: APR-407
  • NCT ID: NCT02098343

Conditions

  • Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53

Interventions

DrugSynonymsArms
APR-246Phase Ib. APR-246 + Carboplatin/PLD.
Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)Phase Ib. APR-246 + Carboplatin/PLD.

Purpose

The purpose of this study is to make a preliminary assessment of the efficacy of a combined APR-246 and carboplatin/PLD chemotherapy regimen, compared with carboplatin/PLD chemotherapy regimen alone, in patients with platinum sensitive recurrent high grade serous ovarian cancer (HGSOC) with mutated p53. In addition, the study aims to assess the safety profile of the combined APR-246 and carboplatin/PLD chemotherapy regimen compared with carboplatin/PLD chemotherapy regimen alone, to evaluate potential biomarkers, and to assess the biological activity in tumor and surrogate tissues. The trial will enroll up to a maximum of 400 patients.

Trial Arms

NameTypeDescriptionInterventions
Phase Ib. APR-246 + Carboplatin/PLD.ExperimentalDose escalation of APR-246.
  • APR-246
  • Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
Phase II: Arm A. APR-246 + Carboplatin/PLD.ExperimentalExperimental
  • APR-246
  • Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
Phase II: Arm B. Carboplatin/PLD.Active ComparatorActive Comparator
  • Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed High Grade Serous Ovarian Cancer, and positive nuclear immunohistochemical
             (IHC) staining for p53

          -  Disease Progression between 6-24 months after a first or second platinum based regimen

          -  At least a single measurable lesion. Phase II patients only

          -  Adequate organ function prior to registration

          -  Toxicities from previous cancer therapies must have recovered to grade 1 (defined by
             Common Terminology Criteria for Adverse Events [CTCAE] 4.0) Chronic stable grade 2
             peripheral neuropathy secondary to neurotoxicity from prior therapies may be
             considered on a case by case basis

          -  ECOG performance status of 0 to 1

        Exclusion Criteria:

          -  Prior exposure to cumulative doses of doxorubicin >400 mg/m2 or epirubicin >720 mg/m2

          -  History of allergic reactions to carboplatin, platinum containing compounds or
             mannitol and/or hypersensitivity to PLD or to any of the excipients

          -  Unable to undergo imaging by either CT scan or MRI

          -  Evidence of any other medical conditions (such as psychiatric illness, infectious
             diseases, neurological conditions, physical examination or laboratory findings) that
             may interfere with the planned treatment, affect patient compliance or place the
             patient at high risk from treatment related complications

          -  Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma
             in situ)

          -  Is taking concurrent (or within 4 week prior to registration) chemotherapy,
             immunotherapy, radiotherapy, or any ancillary therapy that is considered to be
             investigational (i.e., used for non-approved indications(s) and in the context of a
             research investigation). Supportive care measures are allowed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase Ib: Dose-limiting toxicities (DLT) (see Description) of combined APR-246 and carboplatin/PLD regimen
Time Frame:Until the end of the first treatment cycle, i.e., Day 28
Safety Issue:
Description:DLT: Hematological and non-hematological toxicities according to grade/days stated in the protocol.

Secondary Outcome Measures

Measure:Phase II: Overall Survival (OS)
Time Frame:Up to 24 months
Safety Issue:
Description:Time frame from registration to the date of death from any cause.
Measure:Phase II: Overall Response Rate (RR)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase II: Safety Profile (see Description) of combined APR-246 and carboplatin/PLD regimen or the carboplatin/PLD regimen alone
Time Frame:Until 30 days after the last administration of study treatment to the patient.
Safety Issue:
Description:Safety Analysis: Adverse events will be summarized by body system, preferred term, severity, and relationship to treatment. Serious adverse events, deaths, and AEs leading to early discontinuation of study drug will be summarized. Laboratory parameters will be summarized.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Aprea Therapeutics AB

Trial Keywords

  • Ovarian cancer
  • Ovarian carcinoma
  • High Grade Serous Ovarian Cancer
  • Recurrent Cancer
  • Resistant Cancer

Last Updated

January 30, 2018