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

Sponsor

Aprea Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT02098343

Collaborator

(none)

200

Enrollment

Locations

Arms

Actual Duration (Months)

3.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Platinum Sensitive Recurrent High-grade Serous Ovarian Cancer With Mutated p53	Drug: APR-246 Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2014

Actual Primary Completion Date :

Apr 1, 2019

Actual Study Completion Date :

Apr 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase Ib. APR-246 + Carboplatin/PLD. Dose escalation of APR-246.	Drug: APR-246 Intravenous infusion. Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) Intravenous infusion.
Experimental: Phase II: Arm A. APR-246 + Carboplatin/PLD. Experimental	Drug: APR-246 Intravenous infusion. Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) Intravenous infusion.
Active Comparator: Phase II: Arm B. Carboplatin/PLD. Active Comparator	Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) Intravenous infusion.

Arm

Intervention/Treatment

Experimental: Phase Ib. APR-246 + Carboplatin/PLD.

Dose escalation of APR-246.

Drug: APR-246

Intravenous infusion.

Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Intravenous infusion.

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

Experimental

Drug: APR-246

Intravenous infusion.

Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Intravenous infusion.

Active Comparator: Phase II: Arm B. Carboplatin/PLD.

Active Comparator

Drug: Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD)

Intravenous infusion.

Outcome Measures

Primary Outcome Measures

Phase Ib: Dose-limiting toxicities (DLT) (see Description) of combined APR-246 and carboplatin/PLD regimen [Until the end of the first treatment cycle, i.e., Day 28]
DLT: Hematological and non-hematological toxicities according to grade/days stated in the protocol.
Phase Ib: Safety Profile (see Description) of combined APR-246 and carboplatin/PLD regimen [Until 30 days after the last administration of study treatment to the patient]
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.
Phase Ib: Maximum observed plasma concentration (Cmax) of APR-246 [Until Day 5 in cycle 1]
Phase Ib: Area under the plasma concentration-time curve (AUC) of APR-246 [Until Day 5 in cycle 1]
Phase II: Progression Free Survival (PFS) [Up to 24 months]

Secondary Outcome Measures

Phase II: Overall Survival (OS) [Up to 24 months]
Time frame from registration to the date of death from any cause.
Phase II: Overall Response Rate (RR) [Up to 24 months]
Phase II: Safety Profile (see Description) of combined APR-246 and carboplatin/PLD regimen or the carboplatin/PLD regimen alone [Until 30 days after the last administration of study treatment to the patient.]
Safety Analysis: Adverse events 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed High Grade Serous Ovarian Cancer, and positive nuclear immunohistochemical (IHC) staining for p53
Disease Progression between 6-24 months after a first or second platinum based regimen
At least a single measurable lesion. Phase II patients only
Adequate organ function prior to registration
Toxicities from previous cancer therapies must have recovered to grade 1 (defined by Common Terminology Criteria for Adverse Events [CTCAE] 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 1

Exclusion Criteria:

Prior exposure to cumulative doses of doxorubicin >400 mg/m2 or epirubicin >720 mg/m2
History of allergic reactions to carboplatin, platinum containing compounds or mannitol and/or 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 week 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA	Los Angeles	California	United States	90095
2	University of Chicago	Chicago	Illinois	United States	60637
3	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
6	Oregon Health & Science University	Portland	Oregon	United States	97239
7	The University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
8	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
9	UPMC Hillman Cancer Center, Magee-Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
10	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
11	Parkland, UT Southwestern Medical Center	Dallas	Texas	United States	75390
12	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
13	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
14	Massey Cancer Center, Virginia Commonwealth University	Richmond	Virginia	United States	23298
15	Swedish Cancer Institute	Seattle	Washington	United States	98104
16	Antwerp University Hospital	Antwerpen		Belgium	2650
17	Institut Jules Bordet	Brussels		Belgium	1000
18	Cliniques Universitaires Saint Luc	Brussels		Belgium	B-1200
19	Medische oncologie, Universitair Ziekenhuis Gent	Gent		Belgium	9000
20	Leuven University Hospitals	Leuven		Belgium	B-3000
21	Centre Léon Bérard	Lyon		France	69373
22	Centre Hospitalier Lyon Sud	Lyon		France	69495
23	Centre Catherine de Sienne	Nantes		France	44202
24	Institut Curie	Paris		France	75005
25	Hôpital des Diaconesses (Site Reuilly)	Paris		France	75012
26	Centre Paul Strass	Strasbourg		France	67065
27	Institut Gustave Roussy	Villejuif		France	94805
28	Praxisklinik, Krebsheilkunde für Frauen	Berlin		Germany	10367
29	Charité Campus Virchow-Klinikum	Berlin		Germany	13353
30	Universitätsklinikum Carl Gustav Carus	Dresden		Germany	01307
31	Universitätsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
32	Universitätsfrauenklinik Ulm	Ulm		Germany	89075
33	Academisch Medisch Centrum	Amsterdam		Netherlands	1105 AZ
34	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9700 RB
35	Leids Universitair Medisch Centrum	Leiden		Netherlands	2300 RC
36	Academisch Ziekenhuis Maastricht	Maastricht		Netherlands	6229 HX
37	Institut Català d'Oncologia, Hospital Germans Trias i Pujol	Badalona		Spain	08916
38	Hospital Vall d'Hebron	Barcelona		Spain	08035
39	Hospital Universitario Reina Sofia	Córdoba		Spain	14004
40	Centro Oncologico MD Anderson	Madrid		Spain	28033
41	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
42	Hospital Universitario Fundación Jiménez Díaz	Madrid		Spain	28040
43	Hospital Universitario HM Sanchinarro	Madrid		Spain	28050
44	Hospital Universitario Virgen de la Victoria	Málaga		Spain	29010
45	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
46	Hospital Universitario Araba	Vitoria-Gasteiz		Spain	01009
47	Hospital Clínico Universitario Lozano Blesa	Zaragosa		Spain	50009
48	Karolinska University Hospital	Stockholm		Sweden	SE-171 76
49	Bristol Haematology & Oncology Centre, University Hospitals Bristol	Bristol		United Kingdom	BS2 8ED
50	Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital	Cambridge		United Kingdom	CB2 0QQ
51	Edinburgh Cancer Research Centre, The University of Edinburgh	Edinburgh		United Kingdom	EH4 2XR
52	The Clatterbridge Cancer Center NHS Foundation Trust	Liverpool		United Kingdom	CH63 4JY
53	The Royal Marsden NHS Foundation Trust	London		United Kingdom	SM2 5PT
54	Imperial College London, Hammersmith Hospital Campus	London		United Kingdom	W12 0NN
55	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX