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
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
1 other identifier
interventional
247
8 countries
55
Brief Summary
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2014
Longer than P75 for phase_1
55 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2014
CompletedFirst Submitted
Initial submission to the registry
March 19, 2014
CompletedFirst Posted
Study publicly available on registry
March 28, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2019
CompletedResults Posted
Study results publicly available
September 21, 2022
CompletedMarch 17, 2025
March 1, 2025
5.1 years
March 19, 2014
June 1, 2022
March 6, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase Ib: Dose-limiting Toxicities (DLT) (See Description) of Combined APR-246 and Carboplatin/PLD Regimen
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)
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 Outcomes (1)
Phase Ib and Phase II: Overall Response Rate (RR)
Up to 24 months
Study Arms (5)
Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD.
EXPERIMENTALDose escalation of APR-246.
Phase II: Arm A. APR-246 + Carboplatin/PLD.
EXPERIMENTALExperimental
Phase II: Arm B. Carboplatin/PLD.
ACTIVE COMPARATORActive Comparator
Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD.
EXPERIMENTALDose escalation of APR-246.
Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD.
EXPERIMENTALDose escalation of APR-246.
Interventions
Intravenous infusion.
Intravenous infusion.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (55)
UCLA
Los Angeles, California, 90095, United States
University of Chicago
Chicago, Illinois, 60637, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
The University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
UPMC Hillman Cancer Center, Magee-Womens Hospital
Pittsburgh, Pennsylvania, 15213, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Parkland, UT Southwestern Medical Center
Dallas, Texas, 75390, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Massey Cancer Center, Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Swedish Cancer Institute
Seattle, Washington, 98104, United States
Antwerp University Hospital
Antwerp, 2650, Belgium
Institut Jules Bordet
Brussels, 1000, Belgium
Cliniques Universitaires Saint Luc
Brussels, B-1200, Belgium
Medische oncologie, Universitair Ziekenhuis Gent
Ghent, 9000, Belgium
Leuven University Hospitals
Leuven, B-3000, Belgium
Centre Léon Bérard
Lyon, 69373, France
Centre Hospitalier Lyon Sud
Lyon, 69495, France
Centre Catherine de Sienne
Nantes, 44202, France
Institut Curie
Paris, 75005, France
Hôpital des Diaconesses (Site Reuilly)
Paris, 75012, France
Centre Paul Strass
Strasbourg, 67065, France
Institut Gustave Roussy
Villejuif, 94805, France
Praxisklinik, Krebsheilkunde für Frauen
Berlin, 10367, Germany
Charité Campus Virchow-Klinikum
Berlin, 13353, Germany
Universitätsklinikum Carl Gustav Carus
Dresden, 01307, Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246, Germany
Universitätsfrauenklinik Ulm
Ulm, 89075, Germany
Academisch Medisch Centrum
Amsterdam, 1105 AZ, Netherlands
Universitair Medisch Centrum Groningen
Groningen, 9700 RB, Netherlands
Leids Universitair Medisch Centrum
Leiden, 2300 RC, Netherlands
Academisch Ziekenhuis Maastricht
Maastricht, 6229 HX, Netherlands
Institut Català d'Oncologia, Hospital Germans Trias i Pujol
Badalona, 08916, Spain
Hospital Vall d'Hebron
Barcelona, 08035, Spain
Hospital Universitario Reina Sofia
Córdoba, 14004, Spain
Centro Oncologico MD Anderson
Madrid, 28033, Spain
Hospital Universitario Ramón y Cajal
Madrid, 28034, Spain
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040, Spain
Hospital Universitario HM Sanchinarro
Madrid, 28050, Spain
Hospital Universitario Virgen de la Victoria
Málaga, 29010, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Hospital Universitario Araba
Vitoria-Gasteiz, 01009, Spain
Hospital Clínico Universitario Lozano Blesa
Zaragoza, 50009, Spain
Karolinska University Hospital
Stockholm, SE-171 76, Sweden
Bristol Haematology & Oncology Centre, University Hospitals Bristol
Bristol, BS2 8ED, United Kingdom
Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
Cambridge, CB2 0QQ, United Kingdom
Edinburgh Cancer Research Centre, The University of Edinburgh
Edinburgh, EH4 2XR, United Kingdom
The Clatterbridge Cancer Center NHS Foundation Trust
Liverpool, CH63 4JY, United Kingdom
The Royal Marsden NHS Foundation Trust
London, SM2 5PT, United Kingdom
Imperial College London, Hammersmith Hospital Campus
London, W12 0NN, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Related Publications (2)
Lehmann S, Bykov VJ, Ali D, Andren O, Cherif H, Tidefelt U, Uggla B, Yachnin J, Juliusson G, Moshfegh A, Paul C, Wiman KG, Andersson PO. Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. J Clin Oncol. 2012 Oct 10;30(29):3633-9. doi: 10.1200/JCO.2011.40.7783. Epub 2012 Sep 10.
PMID: 22965953BACKGROUNDDeneberg S, Cherif H, Lazarevic V, Andersson PO, von Euler M, Juliusson G, Lehmann S. An open-label phase I dose-finding study of APR-246 in hematological malignancies. Blood Cancer J. 2016 Jul 15;6(7):e447. doi: 10.1038/bcj.2016.60. No abstract available.
PMID: 27421096BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Medical Advisor
- Organization
- Aprea Therapeutics
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 19, 2014
First Posted
March 28, 2014
Study Start
March 1, 2014
Primary Completion
April 1, 2019
Study Completion
April 1, 2019
Last Updated
March 17, 2025
Results First Posted
September 21, 2022
Record last verified: 2025-03