Back to resultsp53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246
Primary Purpose
High-grade Serous Ovarian Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
APR-246
Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
Sponsored by
About this trial
This is an interventional treatment trial for High-grade Serous Ovarian Cancer focused on measuring Ovarian Cancer, Ovarian Carcinoma, High Grade Serous Ovarian Cancer, Recurrent Cancer, Resistant Cancer
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
Sites / Locations
- Medische oncologie, Universitair Ziekenhuis Gent
- Leuven University Hospitals
- Centre Hospitalier Universitaire de Liège
- Institut Català d'Oncologia, Hospital Germans Trias i Pujol
- Hospital Vall d'Hebron
- Hospital Universitario Fundación Jiménez Díaz
- Hospital Universitario HM Sanchinarro
- Hospital Clinico Universitario de Valencia
- Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
- Edinburgh Cancer Research Centre, The University of Edinburgh
- The Royal Marsden NHS Foundation Trust
- Imperial College London, Hammersmith Hospital Campus
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
APR-246 + PLD
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03268382
Brief Title
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
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
July 31, 2017 (Actual)
Primary Completion Date
July 10, 2019 (Actual)
Study Completion Date
July 10, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aprea Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High-grade Serous Ovarian Cancer
Keywords
Ovarian Cancer, Ovarian Carcinoma, High Grade Serous Ovarian Cancer, Recurrent Cancer, Resistant Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
APR-246 + PLD
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
APR-246
Intervention Description
Intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
Intervention Description
Intravenous infusion
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
Up to 18 months
Secondary Outcome Measure Information:
Title
Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen
Description
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.
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)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charlie Gourley, BSc, MB ChB, PhD, FRCP
Organizational Affiliation
Edinburgh Cancer Research Centre, The University of Edinburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medische oncologie, Universitair Ziekenhuis Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Leuven University Hospitals
City
Leuven
ZIP/Postal Code
B-3000
Country
Belgium
Facility Name
Centre Hospitalier Universitaire de Liège
City
Liège
ZIP/Postal Code
B-4000
Country
Belgium
Facility Name
Institut Català d'Oncologia, Hospital Germans Trias i Pujol
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario Fundación Jiménez Díaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario HM Sanchinarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
Edinburgh Cancer Research Centre, The University of Edinburgh
City
Edinburgh
ZIP/Postal Code
EH4 2XR
Country
United Kingdom
Facility Name
The Royal Marsden NHS Foundation Trust
City
London
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
Imperial College London, Hammersmith Hospital Campus
City
London
ZIP/Postal Code
W12 0NN
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
22965953
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.
Results Reference
background
PubMed Identifier
27421096
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.
Results Reference
background
Links:
URL
http://www.aprea.com
Description
Aprea Therapeutics AB's website (Sponsor)
Learn more about this trial
p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246
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