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.
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
Drug | Synonyms | Arms |
---|
APR-246 | | APR-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
Name | Type | Description | Interventions |
---|
APR-246 + PLD | Experimental | | - 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: | Completed |
Lead Sponsor: | Aprea Therapeutics |
Trial Keywords
- Ovarian Cancer
- Ovarian Carcinoma
- High Grade Serous Ovarian Cancer
- Recurrent Cancer
- Resistant Cancer
Last Updated
October 10, 2019