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

NCT ID: NCT02098343

Last Updated: 2025-03-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

247 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2019-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD.

Dose escalation of APR-246.

Group Type EXPERIMENTAL

APR-246

Intervention Type DRUG

Intravenous infusion.

Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Intervention Type DRUG

Intravenous infusion.

Phase II: Arm A. APR-246 + Carboplatin/PLD.

Experimental

Group Type EXPERIMENTAL

APR-246

Intervention Type DRUG

Intravenous infusion.

Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Intervention Type DRUG

Intravenous infusion.

Phase II: Arm B. Carboplatin/PLD.

Active Comparator

Group Type ACTIVE_COMPARATOR

Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Intervention Type DRUG

Intravenous infusion.

Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD.

Dose escalation of APR-246.

Group Type EXPERIMENTAL

APR-246

Intervention Type DRUG

Intravenous infusion.

Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Intervention Type DRUG

Intravenous infusion.

Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD.

Dose escalation of APR-246.

Group Type EXPERIMENTAL

APR-246

Intervention Type DRUG

Intravenous infusion.

Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Intervention Type DRUG

Intravenous infusion.

Interventions

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APR-246

Intravenous infusion.

Intervention Type DRUG

Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Intravenous infusion.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Aprea Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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UCLA

Los Angeles, California, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

The University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center, Magee-Womens Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Parkland, UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Massey Cancer Center, Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Antwerp University Hospital

Antwerp, , Belgium

Site Status

Institut Jules Bordet

Brussels, , Belgium

Site Status

Cliniques Universitaires Saint Luc

Brussels, , Belgium

Site Status

Medische oncologie, Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

Leuven University Hospitals

Leuven, , Belgium

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Centre Hospitalier Lyon Sud

Lyon, , France

Site Status

Centre Catherine de Sienne

Nantes, , France

Site Status

Institut Curie

Paris, , France

Site Status

Hôpital des Diaconesses (Site Reuilly)

Paris, , France

Site Status

Centre Paul Strass

Strasbourg, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Praxisklinik, Krebsheilkunde für Frauen

Berlin, , Germany

Site Status

Charité Campus Virchow-Klinikum

Berlin, , Germany

Site Status

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Site Status

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

Universitätsfrauenklinik Ulm

Ulm, , Germany

Site Status

Academisch Medisch Centrum

Amsterdam, , Netherlands

Site Status

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Site Status

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Site Status

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Site Status

Institut Català d'Oncologia, Hospital Germans Trias i Pujol

Badalona, , Spain

Site Status

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Reina Sofia

Córdoba, , Spain

Site Status

Centro Oncologico MD Anderson

Madrid, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Site Status

Hospital Universitario HM Sanchinarro

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Hospital Universitario Araba

Vitoria-Gasteiz, , Spain

Site Status

Hospital Clínico Universitario Lozano Blesa

Zaragoza, , Spain

Site Status

Karolinska University Hospital

Stockholm, , Sweden

Site Status

Bristol Haematology & Oncology Centre, University Hospitals Bristol

Bristol, , United Kingdom

Site Status

Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Edinburgh Cancer Research Centre, The University of Edinburgh

Edinburgh, , United Kingdom

Site Status

The Clatterbridge Cancer Center NHS Foundation Trust

Liverpool, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status

Imperial College London, Hammersmith Hospital Campus

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Countries

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United States Belgium France Germany Netherlands Spain Sweden United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 22965953 (View on PubMed)

Deneberg 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.

Reference Type BACKGROUND
PMID: 27421096 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.aprea.com

Aprea Therapeutics AB's website (Sponsor)

Other Identifiers

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APR-407

Identifier Type: -

Identifier Source: org_study_id

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