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
- Conditions
- Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53
- Interventions
- Registration Number
- NCT02098343
- Lead Sponsor
- Aprea Therapeutics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 247
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD. APR-246 Dose escalation of APR-246. Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD. Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) Dose escalation of APR-246. Phase II: Arm A. APR-246 + Carboplatin/PLD. APR-246 Experimental Phase II: Arm A. APR-246 + Carboplatin/PLD. Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) Experimental Phase II: Arm B. Carboplatin/PLD. Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) Active Comparator Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD. APR-246 Dose escalation of APR-246. Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD. Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) Dose escalation of APR-246. Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD. APR-246 Dose escalation of APR-246. Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD. Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) Dose escalation of APR-246.
- Primary Outcome Measures
Name Time Method Phase Ib: Dose-limiting Toxicities (DLT) (See Description) of Combined APR-246 and Carboplatin/PLD Regimen 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.
Phase Ib and II: Progression Free Survival (PFS) 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.
- Secondary Outcome Measures
Name Time Method Phase Ib and Phase II: Overall Response Rate (RR) 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.
Trial Locations
- Locations (55)
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Centre Léon Bérard
🇫🇷Lyon, France
University of Chicago
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Leuven University Hospitals
🇧🇪Leuven, Belgium
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Institut Curie
🇫🇷Paris, France
Charité Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Centre Catherine de Sienne
🇫🇷Nantes, France
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Belgium
Medische oncologie, Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Centre Hospitalier Lyon Sud
🇫🇷Lyon, France
Praxisklinik, Krebsheilkunde für Frauen
🇩🇪Berlin, Germany
Institut Gustave Roussy
🇫🇷Villejuif, France
Academisch Medisch Centrum
🇳🇱Amsterdam, Netherlands
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Universitätsfrauenklinik Ulm
🇩🇪Ulm, Germany
Leids Universitair Medisch Centrum
🇳🇱Leiden, Netherlands
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Centro Oncologico MD Anderson
🇪🇸Madrid, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Bristol Haematology & Oncology Centre, University Hospitals Bristol
🇬🇧Bristol, United Kingdom
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Karolinska University Hospital
🇸🇪Stockholm, Sweden
Hospital Universitario Fundación Jiménez DÃaz
🇪🇸Madrid, Spain
Edinburgh Cancer Research Centre, The University of Edinburgh
🇬🇧Edinburgh, United Kingdom
The Clatterbridge Cancer Center NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Imperial College London, Hammersmith Hospital Campus
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Hôpital des Diaconesses (Site Reuilly)
🇫🇷Paris, France
Centre Paul Strass
🇫🇷Strasbourg, France
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital ClÃnico Universitario Lozano Blesa
🇪🇸Zaragosa, Spain
UCLA
🇺🇸Los Angeles, California, United States
Parkland, UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
The University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Institut Català d'Oncologia, Hospital Germans Trias i Pujol
🇪🇸Badalona, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Hospital Universitario Araba
🇪🇸Vitoria-Gasteiz, Spain
UPMC Hillman Cancer Center, Magee-Womens Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Institut Jules Bordet
🇧🇪Brussels, Belgium
Antwerp University Hospital
🇧🇪Antwerpen, Belgium
Massey Cancer Center, Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States