Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53 Clinical Trial
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
| Verified date | February 2024 |
| Source | Aprea Therapeutics |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 247 |
| Est. completion date | April 2019 |
| Est. primary completion date | April 2019 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Antwerp University Hospital | Antwerpen | |
| Belgium | Cliniques Universitaires Saint Luc | Brussels | |
| Belgium | Institut Jules Bordet | Brussels | |
| Belgium | Medische oncologie, Universitair Ziekenhuis Gent | Gent | |
| Belgium | Leuven University Hospitals | Leuven | |
| France | Centre Hospitalier Lyon Sud | Lyon | |
| France | Centre Léon Bérard | Lyon | |
| France | Centre Catherine de Sienne | Nantes | |
| France | Hôpital des Diaconesses (Site Reuilly) | Paris | |
| France | Institut Curie | Paris | |
| France | Centre Paul Strass | Strasbourg | |
| France | Institut Gustave Roussy | Villejuif | |
| Germany | Charité Campus Virchow-Klinikum | Berlin | |
| Germany | Praxisklinik, Krebsheilkunde für Frauen | Berlin | |
| Germany | Universitätsklinikum Carl Gustav Carus | Dresden | |
| Germany | Universitätsklinikum Hamburg-Eppendorf | Hamburg | |
| Germany | Universitätsfrauenklinik Ulm | Ulm | |
| Netherlands | Academisch Medisch Centrum | Amsterdam | |
| Netherlands | Universitair Medisch Centrum Groningen | Groningen | |
| Netherlands | Leids Universitair Medisch Centrum | Leiden | |
| Netherlands | Academisch Ziekenhuis Maastricht | Maastricht | |
| Spain | Institut Català d'Oncologia, Hospital Germans Trias i Pujol | Badalona | |
| Spain | Hospital Vall d'Hebron | Barcelona | |
| Spain | Hospital Universitario Reina Sofia | Córdoba | |
| Spain | Centro Oncologico MD Anderson | Madrid | |
| Spain | Hospital Universitario Fundación Jiménez Díaz | Madrid | |
| Spain | Hospital Universitario HM Sanchinarro | Madrid | |
| Spain | Hospital Universitario Ramón y Cajal | Madrid | |
| Spain | Hospital Universitario Virgen de la Victoria | Málaga | |
| Spain | Hospital Clinico Universitario de Valencia | Valencia | |
| Spain | Hospital Universitario Araba | Vitoria-Gasteiz | |
| Spain | Hospital Clínico Universitario Lozano Blesa | Zaragosa | |
| Sweden | Karolinska University Hospital | Stockholm | |
| United Kingdom | Bristol Haematology & Oncology Centre, University Hospitals Bristol | Bristol | |
| United Kingdom | Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital | Cambridge | |
| United Kingdom | 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 Royal Marsden NHS Foundation Trust | London | |
| United Kingdom | The Christie NHS Foundation Trust | Manchester | |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | University of Chicago | Chicago | Illinois |
| United States | Parkland, UT Southwestern Medical Center | Dallas | Texas |
| United States | University of Texas Southwestern Medical Center | Dallas | Texas |
| United States | Barbara Ann Karmanos Cancer Institute | Detroit | Michigan |
| United States | The University of Texas MD Anderson Cancer Center | Houston | Texas |
| United States | UCLA | Los Angeles | California |
| United States | Vanderbilt University Medical Center | Nashville | Tennessee |
| United States | Fox Chase Cancer Center | Philadelphia | Pennsylvania |
| United States | The University of Pennsylvania | Philadelphia | Pennsylvania |
| United States | UPMC Hillman Cancer Center, Magee-Womens Hospital | Pittsburgh | Pennsylvania |
| United States | Oregon Health & Science University | Portland | Oregon |
| United States | Massey Cancer Center, Virginia Commonwealth University | Richmond | Virginia |
| United States | Swedish Cancer Institute | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| Aprea Therapeutics |
United States, Belgium, France, Germany, Netherlands, Spain, Sweden, United Kingdom,
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. — View 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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | 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 | Phase Ib and Phase II: Overall Response Rate (RR) | 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 |