Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Recurrence

Disease Attributes

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Carboplatin

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

APR-246

Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

The purpose of this study is to make a preliminary assessment of the efficacy of a combined APR-246 and carboplatin/PLD chemotherapy regimen, compared with carboplatin/PLD chemotherapy regimen alone, in patients with platinum sensitive recurrent high grade serous ovarian cancer (HGSOC) with mutated p53. In addition, the study aims to assess the safety profile of the combined APR-246 and carboplatin/PLD chemotherapy regimen compared with carboplatin/PLD chemotherapy regimen alone, to evaluate potential biomarkers, and to assess the biological activity in tumor and surrogate tissues. The trial will enroll up to a maximum of 400 patients.

p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246

PiSARRO: p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246

DLT: Hematological and non-hematological toxicities according to grade/days stated in the protocol.

Phase Ib: Progression-free Survival is calculated from date of enrollment to the date of disease progression or death due to any cause, whichever occurs first. Symptomatic deterioration is not considered PD. For a patient without evidence of disease progression or death, Progression-free survival will be censored at the date of last evaluable tumor assessment. Patients with no evaluable tumor assessments will be censored at the date of first study drug administration.

Phase II: Progression-free survival (PFS) based on Blinded Independent Central Review (BICR) is the primary endpoint and is defined as the number of days from the date of randomization to the date of objective disease progression or relapse (according to RECIST v1.1 only) or death due to any cause, whichever occurs first. If neither event occurs, PFS is censored at the date of the last evaluable tumor assessment. Symptomatic deterioration is not considered objective disease progression.

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.

Aprea Therapeutics

Ph1b: All dose groups in Ph1b are combined and reported together due to small numbers in escalation phase:

n=9 at 35mg/kg n=6 at 50mg/kg n=20 at 67.5mg/kg

Ph2: Safety evaluable population is defined as all randomized patients who received any amount of study medication \[APR-246, carboplatin, or PLD\], regardless of duration of treatment.

Dose escalation of APR-246.

APR-246: Intravenous infusion.

Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion.

All dose groups in Ph1b are combined and reported together due to small numbers in escalation phase:

n=9 at 35mg/kg n=6 at 50mg/kg n=20 at 67.5mg/kg

Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD.

Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD.

Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD.

Experimental

APR-246: Intravenous infusion.

Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion.

Phase II: Arm A. APR-246 + Carboplatin/PLD.

Active Comparator

Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion.

Phase II: Arm B. Carboplatin/PLD.

Dose escalation of APR-246.

APR-246: Intravenous infusion.

Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD): Intravenous infusion.

Total

36 patients were enrolled in the Phase Ib study. One patient from the 67.5 mg/kg dose cohort was withdrawn from the study prior to initiating APR-246 treatment due to Investigator's decision.

Age, Categorical

Age, Continuous

Sex: Female, Male

One patient in the 67.5 mg/kg dose cohort (Patient 441-P016) did not meet the eligibility criteria (Exclusion criteria). The eligibility issue for this patient was discovered after the patient had commenced treatment. However, the patient continued the study treatment since it would have been unethical to withdraw the patient from the study.

Race (NIH/OMB)

Netherlands

Sweden

Belgium

United States

United Kingdom

France

Germany

Spain

Region of Enrollment

A total of 36 pts in Ph1b, and 211 patients in Ph2 were enrolled. One patient from the 67.5 mg/kg dose cohort was withdrawn from the study prior to initiating treatment. Another patient in the 67.5 mg/kg dose cohort did not meet the eligibility criteria (Exclusion criteria). The eligibility issue for this patient was discovered after the patient had commenced treatment. However, the patient continued the study treatment since it would have been unethical to withdraw the patient from the study.

Nadeem Mirza, MD MPH Senior Medical Advisor

Phase Ib: Dose-limiting Toxicities (DLT) (See Description) of Combined APR-246 and Carboplatin/PLD Regimen

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246	NCT02098343	Platinum Sensit...	APR-246 Carboplatin and...	18 Years -	Aprea Therapeutics
p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246	NCT02098343	Platinum Sensit...	APR-246 Carboplatin and...	18 Years -	Aprea Therapeutics

Spots Global Cancer Trial Database for carboplatin and pegylated liposomal doxorubicin hydrochloride (pld)