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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 : Active, not recruiting
First Posted : August 31, 2017
Last Update Posted : September 18, 2018
Sponsor:
Information provided by (Responsible Party):
Aprea Therapeutics AB

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.

Condition or disease Intervention/treatment Phase
High-grade Serous Ovarian Cancer Drug: APR-246 Drug: Pegylated Liposomal Doxorubicin Hydrochloride (PLD) Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 31, 2017
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : April 2019


Arm Intervention/treatment
Experimental: APR-246 + PLD Drug: APR-246
Intravenous infusion

Drug: Pegylated Liposomal Doxorubicin Hydrochloride (PLD)
Intravenous infusion




Primary Outcome Measures :
  1. Overall response rate [ Time Frame: Up to 18 months ]
    Overall response rate according to RECIST 1.1


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) rate [ Time Frame: Up to 18 months ]
  2. 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) ]
  3. 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) ]
  4. Maximum observed plasma concentration (Cmax) of PLD [ Time Frame: Until the end of cycle 1 (cycle length is 28 days) ]
  5. Area under the plasma concentration versus time curve (AUC) of PLD [ Time Frame: Until the end of cycle 1 (cycle length is 28 days) ]
  6. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03268382


Locations
Belgium
Medische oncologie, Universitair Ziekenhuis Gent
Gent, Belgium, 9000
Leuven University Hospitals
Leuven, Belgium, B-3000
Centre Hospitalier Universitaire de Liège
Liège, Belgium, B-4000
Spain
Institut Català d'Oncologia, Hospital Germans Trias i Pujol
Badalona, Spain, 08916
Hospital Vall d'Hebron
Barcelona, Spain, 08035
Hospital Universitario Fundación Jiménez Díaz
Madrid, Spain, 28040
Hospital Universitario HM Sanchinarro
Madrid, Spain, 28050
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
United Kingdom
Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
Cambridge, United Kingdom, CB2 0QQ
Edinburgh Cancer Research Centre, The University of Edinburgh
Edinburgh, United Kingdom, EH4 2XR
The Royal Marsden NHS Foundation Trust
London, United Kingdom, SM2 5PT
Imperial College London, Hammersmith Hospital Campus
London, United Kingdom, W12 0NN
Sponsors and Collaborators
Aprea Therapeutics AB
Investigators
Principal Investigator: Charlie Gourley, BSc, MB ChB, PhD, FRCP Edinburgh Cancer Research Centre, The University of Edinburgh

Additional Information:
Publications:
Responsible Party: Aprea Therapeutics AB
ClinicalTrials.gov Identifier: NCT03268382     History of Changes
Other Study ID Numbers: APR-486
First Posted: August 31, 2017    Key Record Dates
Last Update Posted: September 18, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aprea Therapeutics AB:
Ovarian Cancer
Ovarian Carcinoma
High Grade Serous Ovarian Cancer
Recurrent Cancer
Resistant Cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action