Clinical trial NCT02098343: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53
Keywords: Ovarian cancer
Ovarian carcinoma
High Grade Serous Ovarian Cancer
Recurrent Cancer
Resistant Cancer
Lead sponsor: Aprea Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-03-28
Enrollment: 247
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Phase Ib: Dose-limiting Toxicities (DLT) (See Description) of Combined APR-246 and Carboplatin/PLD Regimen
timeFrame: Until the end of the first treatment cycle, i.e., Day 28
measure: Phase Ib and II: Progression Free Survival (PFS)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Phase Ib and Phase II: Overall Response Rate (RR)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: The University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center, Magee-Womens Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Parkland, UT Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Richmond
country: United States
facility: Massey Cancer Center, Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Antwerpen
country: Belgium
facility: Antwerp University Hospital
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Gent
country: Belgium
facility: Medische oncologie, Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Leuven University Hospitals
city: Lyon
country: France
facility: Centre Léon Bérard
city: Lyon
country: France
facility: Centre Hospitalier Lyon Sud
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hôpital des Diaconesses (Site Reuilly)
city: Strasbourg
country: France
facility: Centre Paul Strass
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Praxisklinik, Krebsheilkunde für Frauen
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Ulm
country: Germany
facility: Universitätsfrauenklinik Ulm
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Badalona
country: Spain
facility: Institut Català d'Oncologia, Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Centro Oncologico MD Anderson
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Vitoria-Gasteiz
country: Spain
facility: Hospital Universitario Araba
city: Zaragosa
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology & Oncology Centre, University Hospitals Bristol
city: Cambridge
country: United Kingdom
facility: Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Research Centre, The University of Edinburgh
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Center NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College London, Hammersmith Hospital Campus
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
References:
citation: 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.
citation: 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.