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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| APR-246 + PLD | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| APR-246 | Drug | Intravenous infusion |
| |
| Pegylated Liposomal Doxorubicin Hydrochloride (PLD) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Charlie Gourley, BSc, MB ChB, PhD, FRCP | Edinburgh Cancer Research Centre, The University of Edinburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medische oncologie, Universitair Ziekenhuis Gent | Ghent | 9000 | Belgium | |||
| Leuven University Hospitals |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22965953 | Background | Lehmann S, Bykov VJ, Ali D, Andren O, Cherif H, Tidefelt U, Uggla B, Yachnin J, Juliusson G, Moshfegh A, Paul C, Wiman KG, Andersson PO. Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. J Clin Oncol. 2012 Oct 10;30(29):3633-9. doi: 10.1200/JCO.2011.40.7783. Epub 2012 Sep 10. | |
| 27421096 |
| Label | URL |
|---|---|
| Aprea Therapeutics AB's website (Sponsor) | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | APR-246 (4.5g/6hr) + PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion |
| FG001 | APR-246 (4.5g/3hr) +PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 12, 2017 |
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| Drug |
Intravenous infusion |
|
| 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) |
| Leuven |
| B-3000 |
| Belgium |
| Centre Hospitalier Universitaire de Liège | Liège | B-4000 | Belgium |
| Institut Català d'Oncologia, Hospital Germans Trias i Pujol | Badalona | 08916 | Spain |
| Hospital Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Universitario Fundación Jiménez DÃaz | Madrid | 28040 | Spain |
| Hospital Universitario HM Sanchinarro | Madrid | 28050 | Spain |
| Hospital Clinico Universitario de Valencia | Valencia | 46010 | Spain |
| Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital | Cambridge | CB2 0QQ | United Kingdom |
| Edinburgh Cancer Research Centre, The University of Edinburgh | Edinburgh | EH4 2XR | United Kingdom |
| The Royal Marsden NHS Foundation Trust | London | SM2 5PT | United Kingdom |
| Imperial College London, Hammersmith Hospital Campus | London | W12 0NN | United Kingdom |
| Deneberg S, Cherif H, Lazarevic V, Andersson PO, von Euler M, Juliusson G, Lehmann S. An open-label phase I dose-finding study of APR-246 in hematological malignancies. Blood Cancer J. 2016 Jul 15;6(7):e447. doi: 10.1038/bcj.2016.60. No abstract available. |
| FG002 | APR-246 (4.5g/4hr) +PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion |
| FG003 | APR-246 (3.7g/4hr) +PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion |
| COMPLETED |
|
| NOT COMPLETED |
|
Patients with Pt-resistant HGSOC with TP53 mutation.
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| ID | Title | Description |
|---|---|---|
| BG000 | APR-246 (4.5g/6hr) + PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion |
| BG001 | APR-246 (4.5g/3hr) + PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion |
| BG002 | APR-246 (4.5g/4hr) + PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion |
| BG003 | APR-246 (3.7g/4hr) + PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Count of Participants | Participants | Up to 18 months |
|
|
| |||||||||||||||||||||||||||||||||||
| 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. | Posted | Count of Participants | Participants | 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. Median number of 28d Cycles=2.5 (Min = 1, Max = 14)
AEs were graded according to NCI CTCAE (Version 4.0).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | APR-246 (4.5g/6hr) + PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion | 9 | 28 | 11 | 28 | 28 | 28 |
| EG001 | APR-246 (4.5g/3hr) + PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion | 1 | 3 | 1 | 3 | 3 | 3 |
| EG002 | APR-246 (4.5g/4hr) + PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion | 0 | 2 | 1 | 2 | 2 | 2 |
| EG003 | APR-246 (3.7g/4hr) + PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion | 1 | 3 | 2 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Peritoneal fibrosis | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA (17.1) | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (17.1) | Systematic Assessment |
| |
| Ataxia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (17.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Gastroesophageal reflux disease | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Gastric ulcer | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Edema peripheral | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Device occlusion | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Infusion site vesicles | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Ataxia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dyskinesia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Balance disorder | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Akathisia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Apraxia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dysarthria | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Nystagmus | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Paresthesia | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypophosphatemia | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Lip infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Miliaria | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Nightmare | Psychiatric disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Micturition urgency | Renal and urinary disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Vascular access complication | Injury, poisoning and procedural complications | MedDRA (17.1) | Systematic Assessment |
| |
| Glomerular filtration rate decreased | Investigations | MedDRA (17.1) | Systematic Assessment |
| |
| Vascular disorders | Vascular disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Ear and labyrinth disorders | Ear and labyrinth disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Blepharitis | Eye disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (17.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Medical Advisor | Aprea Therapeutics | 215-948-4119 | info@aprea.com |
| Jun 1, 2022 |
| Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C533410 | eprenetapopt |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Asian |
|
| United Kingdom |
|
| Spain |
|
| Stable Disease (SD) |
|
| Progressive Disease (PD) |
|
| Not Evaluable |
|
| Disease Control Rate (CR+PR+SD) |
|
| OG003 | APR-246 (3.7g/4hr) + PLD | APR-246: Intravenous infusion Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion |
|
|