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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

Primary Purpose

Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
APR-246
Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
Sponsored by
Aprea Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53 focused on measuring Ovarian cancer, Ovarian carcinoma, High Grade Serous Ovarian Cancer, Recurrent Cancer, Resistant Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • UCLA
  • University of Chicago
  • Massachusetts General Hospital
  • Dana Farber Cancer Institute
  • Barbara Ann Karmanos Cancer Institute
  • Oregon Health & Science University
  • The University of Pennsylvania
  • Fox Chase Cancer Center
  • UPMC Hillman Cancer Center, Magee-Womens Hospital
  • Vanderbilt University Medical Center
  • Parkland, UT Southwestern Medical Center
  • University of Texas Southwestern Medical Center
  • The University of Texas MD Anderson Cancer Center
  • Massey Cancer Center, Virginia Commonwealth University
  • Swedish Cancer Institute
  • Antwerp University Hospital
  • Institut Jules Bordet
  • Cliniques Universitaires Saint Luc
  • Medische oncologie, Universitair Ziekenhuis Gent
  • Leuven University Hospitals
  • Centre Léon Bérard
  • Centre Hospitalier Lyon Sud
  • Centre Catherine de Sienne
  • Institut Curie
  • Hôpital des Diaconesses (Site Reuilly)
  • Centre Paul Strass
  • Institut Gustave Roussy
  • Praxisklinik, Krebsheilkunde für Frauen
  • Charité Campus Virchow-Klinikum
  • Universitätsklinikum Carl Gustav Carus
  • Universitätsklinikum Hamburg-Eppendorf
  • Universitätsfrauenklinik Ulm
  • Academisch Medisch Centrum
  • Universitair Medisch Centrum Groningen
  • Leids Universitair Medisch Centrum
  • Academisch Ziekenhuis Maastricht
  • Institut Català d'Oncologia, Hospital Germans Trias i Pujol
  • Hospital Vall d'Hebron
  • Hospital Universitario Reina Sofia
  • Centro Oncologico MD Anderson
  • Hospital Universitario Ramón y Cajal
  • Hospital Universitario Fundación Jiménez Díaz
  • Hospital Universitario HM Sanchinarro
  • Hospital Universitario Virgen de la Victoria
  • Hospital Clinico Universitario de Valencia
  • Hospital Universitario Araba
  • Hospital Clínico Universitario Lozano Blesa
  • Karolinska University Hospital
  • Bristol Haematology & Oncology Centre, University Hospitals Bristol
  • Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
  • Edinburgh Cancer Research Centre, The University of Edinburgh
  • The Clatterbridge Cancer Center NHS Foundation Trust
  • The Royal Marsden NHS Foundation Trust
  • Imperial College London, Hammersmith Hospital Campus
  • The Christie NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Active Comparator

Experimental

Experimental

Arm Label

Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD.

Phase II: Arm A. APR-246 + Carboplatin/PLD.

Phase II: Arm B. Carboplatin/PLD.

Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD.

Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD.

Arm Description

Dose escalation of APR-246.

Experimental

Active Comparator

Dose escalation of APR-246.

Dose escalation of APR-246.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.

Full Information

First Posted
March 19, 2014
Last Updated
September 20, 2022
Sponsor
Aprea Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT02098343
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
March 2014 (Actual)
Primary Completion Date
April 2019 (Actual)
Study Completion Date
April 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aprea Therapeutics

4. Oversight

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53
Keywords
Ovarian cancer, Ovarian carcinoma, High Grade Serous Ovarian Cancer, Recurrent Cancer, Resistant Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
247 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD.
Arm Type
Experimental
Arm Description
Dose escalation of APR-246.
Arm Title
Phase II: Arm A. APR-246 + Carboplatin/PLD.
Arm Type
Experimental
Arm Description
Experimental
Arm Title
Phase II: Arm B. Carboplatin/PLD.
Arm Type
Active Comparator
Arm Description
Active Comparator
Arm Title
Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD.
Arm Type
Experimental
Arm Description
Dose escalation of APR-246.
Arm Title
Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD.
Arm Type
Experimental
Arm Description
Dose escalation of APR-246.
Intervention Type
Drug
Intervention Name(s)
APR-246
Intervention Description
Intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
Intervention Description
Intravenous infusion.
Primary Outcome Measure Information:
Title
Phase Ib: Dose-limiting Toxicities (DLT) (See Description) of Combined APR-246 and Carboplatin/PLD Regimen
Description
DLT: Hematological and non-hematological toxicities according to grade/days stated in the protocol.
Time Frame
Until the end of the first treatment cycle, i.e., Day 28
Title
Phase Ib and II: Progression Free Survival (PFS)
Description
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.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Phase Ib and Phase II: Overall Response Rate (RR)
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 24 months

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 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John A Green, Dr
Organizational Affiliation
Coordinating Investigator. Clatterbridge Centre for Oncology, UK
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
The University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
UPMC Hillman Cancer Center, Magee-Womens Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Parkland, UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Massey Cancer Center, Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Antwerp University Hospital
City
Antwerpen
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Cliniques Universitaires Saint Luc
City
Brussels
ZIP/Postal Code
B-1200
Country
Belgium
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 Léon Bérard
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Lyon
ZIP/Postal Code
69495
Country
France
Facility Name
Centre Catherine de Sienne
City
Nantes
ZIP/Postal Code
44202
Country
France
Facility Name
Institut Curie
City
Paris
ZIP/Postal Code
75005
Country
France
Facility Name
Hôpital des Diaconesses (Site Reuilly)
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Centre Paul Strass
City
Strasbourg
ZIP/Postal Code
67065
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Praxisklinik, Krebsheilkunde für Frauen
City
Berlin
ZIP/Postal Code
10367
Country
Germany
Facility Name
Charité Campus Virchow-Klinikum
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Universitätsfrauenklinik Ulm
City
Ulm
ZIP/Postal Code
89075
Country
Germany
Facility Name
Academisch Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Universitair Medisch Centrum Groningen
City
Groningen
ZIP/Postal Code
9700 RB
Country
Netherlands
Facility Name
Leids Universitair Medisch Centrum
City
Leiden
ZIP/Postal Code
2300 RC
Country
Netherlands
Facility Name
Academisch Ziekenhuis Maastricht
City
Maastricht
ZIP/Postal Code
6229 HX
Country
Netherlands
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 Reina Sofia
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Centro Oncologico MD Anderson
City
Madrid
ZIP/Postal Code
28033
Country
Spain
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
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 Universitario Virgen de la Victoria
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Hospital Universitario Araba
City
Vitoria-Gasteiz
ZIP/Postal Code
01009
Country
Spain
Facility Name
Hospital Clínico Universitario Lozano Blesa
City
Zaragosa
ZIP/Postal Code
50009
Country
Spain
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
SE-171 76
Country
Sweden
Facility Name
Bristol Haematology & Oncology Centre, University Hospitals Bristol
City
Bristol
ZIP/Postal Code
BS2 8ED
Country
United Kingdom
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 Clatterbridge Cancer Center NHS Foundation Trust
City
Liverpool
ZIP/Postal Code
CH63 4JY
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
Facility Name
The Christie NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
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 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246

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