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p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246

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ClinicalTrials.gov Identifier: NCT03268382
Recruitment Status : Completed
First Posted : August 31, 2017
Last Update Posted : October 10, 2019
Sponsor:
Information provided by (Responsible Party):
Aprea Therapeutics

Tracking Information
First Submitted Date  ICMJE August 24, 2017
First Posted Date  ICMJE August 31, 2017
Last Update Posted Date October 10, 2019
Actual Study Start Date  ICMJE July 31, 2017
Actual Primary Completion Date July 10, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2017)
Overall response rate [ Time Frame: Up to 18 months ]
Overall response rate according to RECIST 1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2017)
  • Progression Free Survival (PFS) rate [ Time Frame: Up to 18 months ]
  • Maximum observed plasma concentration (Cmax) of APR-246 [ Time Frame: Until Day 4 in the last treatment cycle (up to 10 cycles, each cycle length is 28 days) ]
  • Area under the plasma concentration versus time curve (AUC) of APR-246 [ Time Frame: Until Day 4 in the last treatment cycle (up to 10 cycles, each cycle length is 28 days) ]
  • Maximum observed plasma concentration (Cmax) of PLD [ Time Frame: Until the end of cycle 1 (cycle length is 28 days) ]
  • Area under the plasma concentration versus time curve (AUC) of PLD [ Time Frame: Until the end of cycle 1 (cycle length is 28 days) ]
  • Incidence of treatment-emergent adverse events with combined APR-246 and PLD regimen [ Time Frame: Until 30 days after the last administration of study treatment to the patient ]
    Safety Analysis: Adverse events (AEs) will be summarized by body system, preferred term, severity, and relationship to treatment. Serious adverse events, deaths, and AEs leading to early discontinuation of study drug will be summarized. Laboratory parameters will be summarized.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE High-grade Serous Ovarian Cancer
Intervention  ICMJE
  • Drug: APR-246
    Intravenous infusion
  • Drug: Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
    Intravenous infusion
Study Arms  ICMJE Experimental: APR-246 + PLD
Interventions:
  • Drug: APR-246
  • Drug: Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 29, 2019)
36
Original Estimated Enrollment  ICMJE
 (submitted: August 29, 2017)
25
Actual Study Completion Date  ICMJE July 10, 2019
Actual Primary Completion Date July 10, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03268382
Other Study ID Numbers  ICMJE APR-486
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aprea Therapeutics
Study Sponsor  ICMJE Aprea Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Charlie Gourley, BSc, MB ChB, PhD, FRCP Edinburgh Cancer Research Centre, The University of Edinburgh
PRS Account Aprea Therapeutics
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP