Platinum-resistant high grade serous ovarian carcinoma MedDRA version: 19.1 Level: LLT Classification code 10033131 Term: Ovarian carcinoma System Organ Class: 100000004864
Conditions
Sponsors
Aprea Therapeutics AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Archived sections from the original formalin fixed paraffin embedded sample reviewed by a gynecological pathologist confirming HGSOC, high grade serous peritoneal cancer or primary fallopian tube cancer and positive immunohistochemistry staining for p53 assessed according to the local methodology (as detailed in the laboratory manual). Cases that do not show p53 staining will not be included. 2. Disease progression between 4 weeks and 6 months after the last platinum-based treatment was administered. 3. At least a single (RECIST 1.1) measurable lesion. 4. Adequate organ function prior to registration: a) Bone marrow reserve • Absolute neutrophil count (ANC) = 1.5 x109/L • Platelets = 100 x 109/L • Hemoglobin = 9 g/dL b) Hepatic • Total bilirubin level 30 mL/min calculated per local practice d) Electrolytes • Potassium within institutional normal ranges. 5. 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 by the Principal Investigator. 6. If of childbearing potential, negative pretreatment serum pregnancy test. 7. If of childbearing potential, willing to use an effective form of contraception (see below) during chemotherapy treatment and for at least 6 months thereafter. Such methods include the following (if using hormonal contraception, this method must be supplemented with a barrier method, preferably male condom): • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: o oral o intravaginal o transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation: o oral o injectable o implantable • intrauterine device (IUD) • intrauterine hormone-releasing system (IUS) • bilateral tubal occlusion • vasectomized partner • true sexual abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Appendix I). 9. = 18 years of age. 10. Signed informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes
Exclusion criteria
Exclusion criteria: 1. Prior exposure to cumulative doses of doxorubicin >400 mg/m2 or epirubicin >720 mg/m2. 2. Confirmed cardiac history of any of the following: a) A myocardial infarct within 6 months prior to registration, b) New York Heart Association Class II or worse heart failure (Appendix II) c) A history of familial long QT syndrome d) Clinically significant pericardial disease e) Electrocardiographic evidence of acute ischemia f) Atrial or ventricular arrhythmias not controlled by medications g) QTc = 480 msec calculated from a single electrocardiogram (ECG) reading or a mean of three ECG readings using Fridericia’s correction (QTcF = QT/RR0.33) h) Bradycardia (< 40 bpm) i) Left ventricular ejection fraction (LVEF) < the institution lower limit of normal as assessed by echocardiogram. 3. Major abdominal surgery or peritonitis within 6 weeks prior to study treatment. 4. Unresolved bowel obstruction, subocclusive disease or the presence of brain metastases. 5. Hypersensitivity to PLD or to any of the excipients. 6. Unable to undergo imaging by either computed tomography (CT) scan or magnetic resonance imaging (MRI). 7. 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. 8. Breast feeding. 9. Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma in situ). 10. Known HIV positive status, active hepatitis B or C status. 11. 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 |
|---|---|
| Main Objective: • To assess the preliminary efficacy of APR-246 with PLD chemotherapy in patients with platinum-resistant HGSOC with mutated TP53;Primary end point(s): • Overall response rate according to RECIST 1.1;Timepoint(s) of evaluation of this end point: Please refer to protocol; Secondary Objective: • To evaluate the pharmacokinetics (PK) of methylene quinuclidinone (if possible) and APR-246 when administered with PLD chemotherapy • To evaluate cardiac safety of APR-246 when administered with PLD chemotherapy • To assess the safety and tolerability of APR-246 with PLD chemotherapy in patients with platinum-resistant HGSOC with mutated TP53 • To assess: o Duration of response (complete or partial response) o Progression-free survival (PFS) by assessment of cancer antigen 125 (CA-125) o PFS by RECIST 1.1 • To evaluate potential biomarkers and tumor activity based on CA-125 • To assess the biological activity in tumor and surrogate tissues | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • PFS rate, defined as the time from registration to the time of disease progression or relapse (according to RECIST 1.1 only) or death, or the date of last tumor assessment without any such event (censored observation) • PK profiles of methylene quinuclidinone (if possible) and APR-246 and concentration of PLD in plasma • Cardiac profile of APR-246 and concentration of PLD • The safety profile (adverse events [AEs], laboratory assessments, physical findings and biomarkers) of APR 246 and PLD chemotherapy • Duration of response (complete or partial response) • Progression-free survival (PFS) by assessment of CA-125 • Evaluation of potential biomarkers • Biological activity in tumor and surrogate tissues ;Timepoint(s) of evaluation of this end point: Please refer to protocol | — |
Countries
Belgium, Spain, United Kingdom
Contacts
Public ContactClinical Operations
Theradex (Europe) Ltd
Outcome results
None listed