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

February 27, 2024 updated by: Aprea Therapeutics

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

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

247

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Antwerpen, Belgium, 2650
        • Antwerp University Hospital
      • Brussels, Belgium, 1000
        • Institut Jules Bordet
      • Brussels, Belgium, B-1200
        • Cliniques Universitaires Saint Luc
      • Gent, Belgium, 9000
        • Medische oncologie, Universitair Ziekenhuis Gent
      • Leuven, Belgium, B-3000
        • Leuven University Hospitals
      • Lyon, France, 69373
        • Centre Leon Berard
      • Lyon, France, 69495
        • Centre Hospitalier Lyon Sud
      • Nantes, France, 44202
        • Centre Catherine De Sienne
      • Paris, France, 75005
        • Institut Curie
      • Paris, France, 75012
        • Hôpital des Diaconesses (Site Reuilly)
      • Strasbourg, France, 67065
        • Centre Paul Strass
      • Villejuif, France, 94805
        • Institut Gustave Roussy
      • Berlin, Germany, 13353
        • Charité Campus Virchow-Klinikum
      • Berlin, Germany, 10367
        • Praxisklinik, Krebsheilkunde für Frauen
      • Dresden, Germany, 01307
        • Universitatsklinikum Carl Gustav Carus
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf
      • Ulm, Germany, 89075
        • Universitätsfrauenklinik Ulm
      • Amsterdam, Netherlands, 1105 AZ
        • Academisch Medisch Centrum
      • Groningen, Netherlands, 9700 RB
        • Universitair Medisch Centrum Groningen
      • Leiden, Netherlands, 2300 RC
        • Leids Universitair Medisch Centrum
      • Maastricht, Netherlands, 6229 HX
        • Academisch Ziekenhuis Maastricht
      • Badalona, Spain, 08916
        • Institut Català d'Oncologia, Hospital Germans Trias i Pujol
      • Barcelona, Spain, 08035
        • Hospital Vall d'Hebron
      • Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28040
        • Hospital Universitario Fundación Jiménez Díaz
      • Madrid, Spain, 28050
        • Hospital Universitario HM Sanchinarro
      • Madrid, Spain, 28033
        • Centro Oncológico MD Anderson
      • Málaga, Spain, 29010
        • Hospital Universitario Virgen de la Victoria
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia
      • Vitoria-Gasteiz, Spain, 01009
        • Hospital Universitario Araba
      • Zaragosa, Spain, 50009
        • Hospital Clinico Universitario Lozano Blesa
      • Stockholm, Sweden, SE-171 76
        • Karolinska University Hospital
      • Bristol, United Kingdom, BS2 8ED
        • Bristol Haematology & Oncology Centre, University Hospitals Bristol
      • Cambridge, United Kingdom, CB2 0QQ
        • Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
      • Edinburgh, United Kingdom, EH4 2XR
        • Edinburgh Cancer Research Centre, The University of Edinburgh
      • Liverpool, United Kingdom, CH63 4JY
        • The Clatterbridge Cancer Center NHS Foundation Trust
      • London, United Kingdom, SM2 5PT
        • The Royal Marsden NHS Foundation Trust
      • London, United Kingdom, W12 0NN
        • Imperial College London, Hammersmith Hospital Campus
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS foundation Trust
    • California
      • Los Angeles, California, United States, 90095
        • UCLA
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Barbara Ann Karmanos Cancer Institute
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19104
        • The University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Hillman Cancer Center, Magee-Womens Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75390
        • Parkland, UT Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Massey Cancer Center, Virginia Commonwealth University
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD.
Dose escalation of APR-246.
Intravenous infusion.
Intravenous infusion.
Experimental: Phase II: Arm A. APR-246 + Carboplatin/PLD.
Experimental
Intravenous infusion.
Intravenous infusion.
Active Comparator: Phase II: Arm B. Carboplatin/PLD.
Active Comparator
Intravenous infusion.
Experimental: Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD.
Dose escalation of APR-246.
Intravenous infusion.
Intravenous infusion.
Experimental: Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD.
Dose escalation of APR-246.
Intravenous infusion.
Intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
DLT: Hematological and non-hematological toxicities according to grade/days stated in the protocol.
Until the end of the first treatment cycle, i.e., Day 28
Phase Ib and II: Progression Free Survival (PFS)
Time Frame: Up to 24 months

Phase Ib: Progression-free Survival is calculated from date of enrollment to the date of disease progression or death due to any cause, whichever occurs first. Symptomatic deterioration is not considered PD. For a patient without evidence of disease progression or death, Progression-free survival will be censored at the date of last evaluable tumor assessment. Patients with no evaluable tumor assessments will be censored at the date of first study drug administration.

Phase II: Progression-free survival (PFS) based on Blinded Independent Central Review (BICR) is the primary endpoint and is defined as the number of days from the date of randomization to the date of objective disease progression or relapse (according to RECIST v1.1 only) or death due to any cause, whichever occurs first. If neither event occurs, PFS is censored at the date of the last evaluable tumor assessment. Symptomatic deterioration is not considered objective disease progression.

Up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase Ib and Phase II: Overall Response Rate (RR)
Time Frame: Up to 24 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: John A Green, Dr, Coordinating Investigator. Clatterbridge Centre for Oncology, UK

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2014

Primary Completion (Actual)

April 1, 2019

Study Completion (Actual)

April 1, 2019

Study Registration Dates

First Submitted

March 19, 2014

First Submitted That Met QC Criteria

March 25, 2014

First Posted (Estimated)

March 28, 2014

Study Record Updates

Last Update Posted (Estimated)

February 29, 2024

Last Update Submitted That Met QC Criteria

February 27, 2024

Last Verified

February 1, 2024

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53

Clinical Trials on APR-246

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