High-grade Serous Ovarian Cancer
Conditions
Keywords
Ovarian Cancer, Ovarian Carcinoma, High Grade Serous Ovarian Cancer, Recurrent Cancer, Resistant Cancer
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.
Interventions
DRUGAPR-246
Intravenous infusion
DRUGPegylated Liposomal Doxorubicin Hydrochloride (PLD)
Intravenous infusion
Sponsors
Aprea Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 18 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. Median number of 28d Cycles=2.5 (Min = 1, Max = 14) | Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. AEs were graded according to NCI CTCAE (Version 4.0). Patients with multiple TEAEs were only counted once within a summary category: SOC, PT, maximum grade, or relationship to treatment. Patients with events in more than one category were counted once within each category. |
Countries
Belgium, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| APR-246 (4.5g/6hr) + PLD APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion | 28 |
| APR-246 (4.5g/3hr) + PLD APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion | 3 |
| APR-246 (4.5g/4hr) + PLD APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion | 2 |
| APR-246 (3.7g/4hr) + PLD APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion | 3 |
| Total | 36 |
Baseline characteristics
| Characteristic | Total | APR-246 (4.5g/6hr) + PLD | APR-246 (4.5g/3hr) + PLD | APR-246 (4.5g/4hr) + PLD | APR-246 (3.7g/4hr) + PLD |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 7 Participants | 1 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 21 Participants | 2 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 35 Participants | 27 Participants | 3 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Belgium | 4 participants | 4 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Spain | 21 participants | 21 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment United Kingdom | 11 participants | 3 participants | 3 participants | 2 participants | 3 participants |
| Sex: Female, Male Female | 36 Participants | 28 Participants | 3 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 28 | 1 / 3 | 0 / 2 | 1 / 3 |
| other Total, other adverse events | 28 / 28 | 3 / 3 | 2 / 2 | 3 / 3 |
| serious Total, serious adverse events | 11 / 28 | 1 / 3 | 1 / 2 | 2 / 3 |
Outcome results
Primary
Overall Response Rate (ORR)
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 18 months
Population: A total of 36 patients were enrolled in this Phase II study. Of the 36 patients, 28 patients were in the main study, 4.5g/6hr dose cohort; 8 patients were in the sub-study as follows: 3 patients were in the 4.5g/3hr dose cohort; 2 patients were in the 4.5g/4hr dose cohort and 3 patients were in the 3.7g/4hr dose cohort.~The 23 Efficacy Evaluable Patients from the Main Study (APR-246 (4.5g/6hr) + PLD) are part of the analysis reported below.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| APR-246 (4.5g/6hr) + PLD | Overall Response Rate (ORR) | Not Evaluable | 0 Participants |
| APR-246 (4.5g/6hr) + PLD | Overall Response Rate (ORR) | Stable Disease (SD) | 15 Participants |
| APR-246 (4.5g/6hr) + PLD | Overall Response Rate (ORR) | Disease Control Rate (CR+PR+SD) | 16 Participants |
| APR-246 (4.5g/6hr) + PLD | Overall Response Rate (ORR) | Progressive Disease (PD) | 7 Participants |
| APR-246 (4.5g/6hr) + PLD | Overall Response Rate (ORR) | Partial Response (PR) | 1 Participants |
| APR-246 (4.5g/3hr) + PLD | Overall Response Rate (ORR) | Progressive Disease (PD) | 0 Participants |
| APR-246 (4.5g/3hr) + PLD | Overall Response Rate (ORR) | Not Evaluable | 1 Participants |
| APR-246 (4.5g/3hr) + PLD | Overall Response Rate (ORR) | Disease Control Rate (CR+PR+SD) | 0 Participants |
| APR-246 (4.5g/3hr) + PLD | Overall Response Rate (ORR) | Stable Disease (SD) | 2 Participants |
| APR-246 (4.5g/3hr) + PLD | Overall Response Rate (ORR) | Partial Response (PR) | 0 Participants |
| APR-246 (4.5g/4hr) + PLD | Overall Response Rate (ORR) | Progressive Disease (PD) | 1 Participants |
| APR-246 (4.5g/4hr) + PLD | Overall Response Rate (ORR) | Partial Response (PR) | 0 Participants |
| APR-246 (4.5g/4hr) + PLD | Overall Response Rate (ORR) | Stable Disease (SD) | 1 Participants |
| APR-246 (4.5g/4hr) + PLD | Overall Response Rate (ORR) | Not Evaluable | 0 Participants |
| APR-246 (4.5g/4hr) + PLD | Overall Response Rate (ORR) | Disease Control Rate (CR+PR+SD) | 0 Participants |
| APR-246 (3.7g/4hr) + PLD | Overall Response Rate (ORR) | Not Evaluable | 0 Participants |
| APR-246 (3.7g/4hr) + PLD | Overall Response Rate (ORR) | Stable Disease (SD) | 1 Participants |
| APR-246 (3.7g/4hr) + PLD | Overall Response Rate (ORR) | Partial Response (PR) | 0 Participants |
| APR-246 (3.7g/4hr) + PLD | Overall Response Rate (ORR) | Progressive Disease (PD) | 2 Participants |
| APR-246 (3.7g/4hr) + PLD | Overall Response Rate (ORR) | Disease Control Rate (CR+PR+SD) | 0 Participants |
Secondary
Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen
Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. AEs were graded according to NCI CTCAE (Version 4.0). Patients with multiple TEAEs were only counted once within a summary category: SOC, PT, maximum grade, or relationship to treatment. Patients with events in more than one category were counted once within each category.
Time frame: Treatment emergent adverse events (TEAEs) were defined as AEs that occurred on or after the first dose of study medication up to and including 30 days after last dose. Median number of 28d Cycles=2.5 (Min = 1, Max = 14)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 PLD Related TEAEs | 7 Participants |
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 | 14 Participants |
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious, PLD Related AEs | 2 Participants |
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious, APR-246 Related AEs | 4 Participants |
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious AEs | 11 Participants |
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Died Due to any TEAEs | 0 Participants |
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With PLD Related TEAEs | 24 Participants |
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Treatment-Emergent Adverse Events (TEAEs) | 28 Participants |
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 APR-246 Related TEAEs | 6 Participants |
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Discontinued APR-246 Due to TEAEs | 2 Participants |
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With APR-246 Related TEAEs | 25 Participants |
| APR-246 (4.5g/6hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Discontinued PLD Due to TEAEs | 0 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Discontinued PLD Due to TEAEs | 0 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With APR-246 Related TEAEs | 3 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 | 3 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 APR-246 Related TEAEs | 2 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 PLD Related TEAEs | 2 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious AEs | 1 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious, APR-246 Related AEs | 1 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious, PLD Related AEs | 1 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Discontinued APR-246 Due to TEAEs | 1 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With PLD Related TEAEs | 3 Participants |
| APR-246 (4.5g/3hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Died Due to any TEAEs | 0 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 PLD Related TEAEs | 0 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious, PLD Related AEs | 0 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With APR-246 Related TEAEs | 2 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Discontinued APR-246 Due to TEAEs | 0 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 APR-246 Related TEAEs | 2 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Discontinued PLD Due to TEAEs | 0 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 | 2 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Died Due to any TEAEs | 0 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With PLD Related TEAEs | 2 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious AEs | 1 Participants |
| APR-246 (4.5g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious, APR-246 Related AEs | 1 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 PLD Related TEAEs | 2 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With APR-246 Related TEAEs | 3 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Discontinued PLD Due to TEAEs | 0 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With PLD Related TEAEs | 3 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Discontinued APR-246 Due to TEAEs | 0 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 APR-246 Related TEAEs | 2 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious AEs | 2 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious, PLD Related AEs | 1 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Severity Grade >=3 | 3 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | Who Died Due to any TEAEs | 0 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Serious, APR-246 Related AEs | 1 Participants |
| APR-246 (3.7g/4hr) + PLD | Treatment-emergent Adverse Events With Combined APR-246 and PLD Regimen | With Any Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |