High-grade Serous Ovarian CancerPhase 2NCT03268382
p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246
A Phase 2 study testing APR-246 and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) in people with High-grade Serous Ovarian Cancer, run by Aprea Therapeutics at 12 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- High-grade Serous Ovarian Cancer
- What is being tested?
- APR-246 and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 12 sitesin 3 countries
- Study dates
- 31 Jul 2017to 10 Jul 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
Spain5 sites
Institut Català d'Oncologia, Hospital Germans Trias i Pujol
Badalona, 08916
Hospital Vall d'Hebron
Barcelona, 08035
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Hospital Universitario HM Sanchinarro
Madrid, 28050
Hospital Clinico Universitario de Valencia
Valencia, 46010
United Kingdom4 sites
Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
Cambridge, CB2 0QQ
Edinburgh Cancer Research Centre, The University of Edinburgh
Edinburgh, EH4 2XR
The Royal Marsden NHS Foundation Trust
London, SM2 5PT
Imperial College London, Hammersmith Hospital Campus
London, W12 0NN
Belgium3 sites
Medische oncologie, Universitair Ziekenhuis Gent
Ghent, 9000
Leuven University Hospitals
Leuven, B-3000
Centre Hospitalier Universitaire de Liège
Liège, B-4000
About this study
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
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.
- Conditions
- High-grade Serous Ovarian Cancer
- Being tested
- APR-246, Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
- Keywords
- Ovarian Cancer, Ovarian Carcinoma, High Grade Serous Ovarian Cancer, Recurrent Cancer, Resistant Cancer
- Medical subject headings
- Ovarian Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APR-246Drug
Intravenous infusion
Pegylated Liposomal Doxorubicin Hydrochloride (PLD)Drug
Intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| APR-246 + PLD | Experimental | Not described Receives: Drug: APR-246; Drug: Pegylated Liposomal Doxorubicin Hydrochloride (PLD) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 18 months
Secondary outcomes (1)
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2017
- Study start31 Jul 2017
- Primary completion10 Jul 2019
- Study completion10 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for High-grade Serous Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aprea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Charlie Gourley, BSc, MB ChB, PhD, FRCP, Principal investigator, Edinburgh Cancer Research Centre, The University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03268382
- Sponsor's protocol ID
- APR-486
- Status last verified
- Mar 2025
- First submitted
- 24 Aug 2017
- Last updated
- 17 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 22965953Deneberg 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.
PubMed 27421096
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03268382
- Acronym / sponsor ID
- APR-486
- Conditions
- High-grade Serous Ovarian Cancer
- Keywords
- Ovarian Cancer, Ovarian Carcinoma, High Grade Serous Ovarian Cancer, Recurrent Cancer, Resistant Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Aprea TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 31 Jul 2017 (actual)
- Primary completion
- 10 Jul 2019 (actual)
- Study completion
- 10 Jul 2019 (actual)
- First posted
- 31 Aug 2017 (actual)
- Results
- Posted 21 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| APR-246 + PLD | Experimental | Drug: APR-246, Drug: Pegylated Liposomal Doxorubicin Hydrochloride (PLD) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APR-246Intravenous infusion | Drug | APR-246 + PLD |
| Pegylated Liposomal Doxorubicin Hydrochloride (PLD)Intravenous infusion | Drug | APR-246 + PLD |
Primary outcome
Overall Response Rate (ORR)
Time frame: Up to 18 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.
1 secondary outcome
Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22965953Lehmann 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.
- Background: PubMed 27421096Deneberg 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.
- Aprea Therapeutics AB's website (Sponsor)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charlie Gourley, BSc, MB ChB, PhD, FRCP principal investigator
Edinburgh Cancer Research Centre, The University of Edinburgh
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing APR-246 and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) in people with High-grade Serous Ovarian Cancer, run by Aprea Therapeutics at 12 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Spain, United Kingdom, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03268382, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2025.