Clinical Trials /

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

NCT03268382

Description:

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.

Related Conditions:
  • Ovarian Serous Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: APR-486
  • NCT ID: NCT03268382

Conditions

  • High-grade Serous Ovarian Cancer

Interventions

DrugSynonymsArms
APR-246APR-246 + PLD
Pegylated Liposomal Doxorubicin Hydrochloride (PLD)APR-246 + PLD

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
APR-246 + PLDExperimental
  • APR-246
  • Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 18 months
Safety Issue:
Description:Overall response rate according to RECIST 1.1

Secondary Outcome Measures

Measure:Progression Free Survival (PFS) rate
Time Frame:Up to 18 months
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Maximum observed plasma concentration (Cmax) of PLD
Time Frame:Until the end of cycle 1 (cycle length is 28 days)
Safety Issue:
Description:
Measure:Area under the plasma concentration versus time curve (AUC) of PLD
Time Frame:Until the end of cycle 1 (cycle length is 28 days)
Safety Issue:
Description:
Measure: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 Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Aprea Therapeutics AB

Trial Keywords

  • Ovarian Cancer
  • Ovarian Carcinoma
  • High Grade Serous Ovarian Cancer
  • Recurrent Cancer
  • Resistant Cancer

Last Updated

October 3, 2017