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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

This study is currently recruiting participants.
Verified October 2017 by Aprea Therapeutics AB
Sponsor:
ClinicalTrials.gov Identifier:
NCT02098343
First Posted: March 28, 2014
Last Update Posted: October 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Aprea Therapeutics AB
  Purpose
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 Intervention 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 Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Aprea Therapeutics AB:

Primary Outcome Measures:
  • Phase Ib: Dose-limiting toxicities (DLT) (see Description) of combined APR-246 and carboplatin/PLD regimen [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Until Day 5 in cycle 1 ]
  • Phase Ib: Area under the plasma concentration-time curve (AUC) of APR-246 [ Time Frame: Until Day 5 in cycle 1 ]
  • Phase II: Progression Free Survival (PFS) [ Time Frame: Up to 24 months ]

Secondary Outcome Measures:
  • Phase II: Overall Survival (OS) [ Time Frame: Up to 24 months ]
    Time frame from registration to the date of death from any cause.

  • Phase II: Overall Response Rate (RR) [ Time Frame: Up to 24 months ]
  • Phase II: Safety Profile (see Description) of combined APR-246 and carboplatin/PLD regimen or the carboplatin/PLD regimen alone [ Time Frame: 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.


Estimated Enrollment: 400
Study Start Date: March 2014
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02098343


Contacts
Contact: Roger Tell, MD PhD +46 8 508 845 04 Roger.Tell@aprea.com

  Show 52 Study Locations
Sponsors and Collaborators
Aprea Therapeutics AB
Investigators
Principal Investigator: John A Green, Dr Coordinating Investigator. Clatterbridge Centre for Oncology, UK
  More Information

Additional Information:
Publications:
Responsible Party: Aprea Therapeutics AB
ClinicalTrials.gov Identifier: NCT02098343     History of Changes
Other Study ID Numbers: APR-407
First Submitted: March 19, 2014
First Posted: March 28, 2014
Last Update Posted: October 11, 2017
Last Verified: October 2017

Keywords provided by Aprea Therapeutics AB:
Ovarian cancer
Ovarian carcinoma
High Grade Serous Ovarian Cancer
Recurrent Cancer
Resistant Cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Liposomal doxorubicin
Carboplatin
Doxorubicin
Antineoplastic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action