p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246

High-grade Serous Ovarian Cancer Clinical Trial

Official title:

PiSARRO-R: p53 Suppressor Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Phase II Study of Systemic Pegylated Liposomal Doxorubicin Chemotherapy With APR-246

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03268382
• Other study ID #: APR-486
• Status: Completed
• Phase: Phase 2
• Start date: July 31, 2017
• Est. completion date: July 10, 2019

Study information

• Verified date: February 2024
• Source: Aprea Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to make a preliminary assessment of the efficacy of a combined APR-246 and PLD chemotherapy regimen in patients with platinum-resistant recurrent high grade serous ovarian cancer (HGSOC) with mutated TP53. In addition, the study aims to assess the safety profile of the combined APR-246 and PLD chemotherapy regimen, to evaluate potential biomarkers, and to assess the biological activity in tumor and surrogate tissues. The trial will enroll at least 25 evaluable patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: July 10, 2019
• Est. primary completion date: July 10, 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 4 weeks - 6 months after the last platinum-based treatment was administered
• At least a single measurable lesion
• Adequate organ function prior to registration
• Toxicities from previous cancer therapies (excluding alopecia) must have recovered to grade 1 (defined by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 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 2

Exclusion Criteria:

• Prior exposure to cumulative doses of doxorubicin >400 mg/m2 or epirubicin >720 mg/m2
• 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 weeks 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. Palliative limited radiation therapy for pain reduction is allowed

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• High-grade Serous Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• APR-246
Intravenous infusion
• Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
Intravenous infusion

Locations

Country	Name	City	State
Belgium	Medische oncologie, Universitair Ziekenhuis Gent	Gent
Belgium	Leuven University Hospitals	Leuven
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Spain	Institut Català d'Oncologia, Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
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	Imperial College London, Hammersmith Hospital Campus	London
United Kingdom	The Royal Marsden NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Aprea Therapeutics

Countries where clinical trial is conducted

Belgium,  Spain,  United Kingdom, 

References & Publications (2)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	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 18 months
Secondary	Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen	Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. AEs were graded according to NCI CTCAE (Version 4.0). Patients with multiple TEAEs were only counted once within a summary category: SOC, PT, maximum grade, or relationship to treatment. Patients with events in more than one category were counted once within each category.	Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. Median number of 28d Cycles=2.5 (Min = 1, Max = 14)

External Links

•   Aprea Therapeutics AB's website (Sponsor)