Clinical trial NCT03268382: p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: High-grade Serous Ovarian Cancer
Keywords: Ovarian Cancer
Ovarian Carcinoma
High Grade Serous Ovarian Cancer
Recurrent Cancer
Resistant Cancer
Lead sponsor: Aprea Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-08-31
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 18 months
Secondary outcomes:
measure: Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen
timeFrame: 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)
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: Medische oncologie, Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Leuven University Hospitals
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Badalona
country: Spain
facility: Institut Català d'Oncologia, Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
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: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College London, Hammersmith Hospital Campus
Study officials:
affiliation: Edinburgh Cancer Research Centre, The University of Edinburgh
name: Charlie Gourley, BSc, MB ChB, PhD, FRCP
role: PRINCIPAL_INVESTIGATOR
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.