Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53Phase 1/2NCT02098343
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
A Phase 1/2 study testing APR-246 and Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) in people with Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53, run by Aprea Therapeutics at 55 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53
- What is being tested?
- APR-246 and Carboplatin 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
- 247 participants
- Where
- 55 sitesin 8 countries
- Study dates
- Mar 2014to Apr 2019
- Phase
- Phase 1/2
- 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 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
Who cannot join
- 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
Trial locations and contacts
55 sites in 8 countries.
55 sites in 8 countries
United States15 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of Chicago
Chicago, Illinois, 60637
Parkland, UT Southwestern Medical Center
Dallas, Texas, 75390
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
UCLA
Los Angeles, California, 90095
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
The University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
UPMC Hillman Cancer Center, Magee-Womens Hospital
Pittsburgh, Pennsylvania, 15213
Oregon Health & Science University
Portland, Oregon, 97239
Massey Cancer Center, Virginia Commonwealth University
Richmond, Virginia, 23298
Swedish Cancer Institute
Seattle, Washington, 98104
Spain11 sites
Institut Català d'Oncologia, Hospital Germans Trias i Pujol
Badalona, 08916
Hospital Vall d'Hebron
Barcelona, 08035
Hospital Universitario Reina Sofia
Córdoba, 14004
Centro Oncologico MD Anderson
Madrid, 28033
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Hospital Universitario HM Sanchinarro
Madrid, 28050
Hospital Universitario Virgen de la Victoria
Málaga, 29010
Hospital Clinico Universitario de Valencia
Valencia, 46010
Hospital Universitario Araba
Vitoria-Gasteiz, 01009
Hospital Clínico Universitario Lozano Blesa
Zaragoza, 50009
France7 sites
Centre Léon Bérard
Lyon, 69373
Centre Hospitalier Lyon Sud
Lyon, 69495
Centre Catherine de Sienne
Nantes, 44202
Institut Curie
Paris, 75005
Hôpital des Diaconesses (Site Reuilly)
Paris, 75012
Centre Paul Strass
Strasbourg, 67065
Institut Gustave Roussy
Villejuif, 94805
United Kingdom7 sites
Bristol Haematology & Oncology Centre, University Hospitals Bristol
Bristol, BS2 8ED
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 Clatterbridge Cancer Center NHS Foundation Trust
Liverpool, CH63 4JY
The Royal Marsden NHS Foundation Trust
London, SM2 5PT
Imperial College London, Hammersmith Hospital Campus
London, W12 0NN
The Christie NHS Foundation Trust
Manchester, M20 4BX
Belgium5 sites
Antwerp University Hospital
Antwerp, 2650
Institut Jules Bordet
Brussels, 1000
Cliniques Universitaires Saint Luc
Brussels, B-1200
Medische oncologie, Universitair Ziekenhuis Gent
Ghent, 9000
Leuven University Hospitals
Leuven, B-3000
Germany5 sites
Praxisklinik, Krebsheilkunde für Frauen
Berlin, 10367
Charité Campus Virchow-Klinikum
Berlin, 13353
Universitätsklinikum Carl Gustav Carus
Dresden, 01307
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Universitätsfrauenklinik Ulm
Ulm, 89075
Netherlands4 sites
Academisch Medisch Centrum
Amsterdam, 1105 AZ
Universitair Medisch Centrum Groningen
Groningen, 9700 RB
Leids Universitair Medisch Centrum
Leiden, 2300 RC
Academisch Ziekenhuis Maastricht
Maastricht, 6229 HX
About this study
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
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.
- Being tested
- APR-246, Carboplatin and 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.
Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)Drug
Intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD. | Experimental | Dose escalation of APR-246. Receives: Drug: APR-246; Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) |
| Phase II: Arm A. APR-246 + Carboplatin/PLD. | Experimental | Experimental Receives: Drug: APR-246; Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) |
| Phase II: Arm B. Carboplatin/PLD. | Active comparator | Active Comparator Receives: Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) |
| Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD. | Experimental | Dose escalation of APR-246. Receives: Drug: APR-246; Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) |
| Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD. | Experimental | Dose escalation of APR-246. Receives: Drug: APR-246; Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Until the end of the first treatment cycle, i.e., Day 28
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.
Measured: Up to 24 months
Secondary outcomes (1)
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.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2014 (estimated)
- Study startMar 2014
- Primary completionApr 2019
- Study completionApr 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 Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 247 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aprea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02098343
- Sponsor's protocol ID
- APR-407
- Status last verified
- Mar 2025
- First submitted
- 19 Mar 2014
- Last updated
- 17 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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: 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
- ClinicalTrials.gov ID
- NCT02098343
- Acronym / sponsor ID
- APR-407
- Keywords
- Ovarian cancer, Ovarian carcinoma, High Grade Serous Ovarian Cancer, Recurrent Cancer, Resistant Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 247 participants (actual)
- Lead sponsor
- Aprea TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Mar 2014 (actual)
- Primary completion
- Apr 2019 (actual)
- Study completion
- Apr 2019 (actual)
- First posted
- 28 Mar 2014 (estimated)
- Results
- Posted 21 Sep 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD. | Experimental | Drug: APR-246, Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)Dose escalation of APR-246. |
| Phase II: Arm A. APR-246 + Carboplatin/PLD. | Experimental | Drug: APR-246, Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)Experimental |
| Phase II: Arm B. Carboplatin/PLD. | Active comparator | Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)Active Comparator |
| Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD. | Experimental | Drug: APR-246, Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)Dose escalation of APR-246. |
| Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD. | Experimental | Drug: APR-246, Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)Dose escalation of APR-246. |
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 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
Key exclusion criteria (6 listed)
- 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)
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 | Phase II: Arm A. APR-246 + Carboplatin/PLD., Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD., Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD., Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD. |
| Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)Intravenous infusion. | Drug | Phase II: Arm A. APR-246 + Carboplatin/PLD., Phase II: Arm B. Carboplatin/PLD., Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD., Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD., Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD. |
Primary outcome
Phase Ib: Dose-limiting Toxicities (DLT) (See Description) of Combined APR-246 and Carboplatin/PLD Regimen
Time frame: Until the end of the first treatment cycle, i.e., Day 28
DLT: Hematological and non-hematological toxicities according to grade/days stated in the protocol.
Phase Ib and II: Progression Free Survival (PFS)
Time frame: Up to 24 months
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.
1 secondary outcome
Phase Ib and Phase II: Overall Response Rate (RR)
Time frame: Up to 24 months
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.
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.
The record lists no contact. Use the official record to reach the sponsor.
55 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing APR-246 and Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) in people with Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53, run by Aprea Therapeutics at 55 sites in 8 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 55 sites in United States, Spain, France, United Kingdom, Belgium and 3 more countries. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Sep 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?
Phase Ib: Dose-limiting Toxicities (DLT) (See Description) of Combined APR-246 and Carboplatin/PLD Regimen (time frame: Until the end of the first treatment cycle, i.e., Day 28). The study lists 2 primary outcomes in all. 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 NCT02098343, 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.