A study of systemic carboplatin/PLD combination chemotherapy with or without APR-246 in patients with Platinum-resistant high grade serous ovarian cancer

Phase 1

• Conditions: Platinum-resistant high grade serous ovarian carcinoma; MedDRA version: 20.0 Level: LLT Classification code 10033131 Term: Ovarian carcinoma System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000265-67-ES
• Lead Sponsor: Aprea Therapeutics AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-05-29
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 25

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 < 1.5 x ULN without hepatic metastasis, and < 4 x ULN with hepatic metastasis
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN without hepatic metastasis, and < 4 x ULN with hepatic metastasis
c) Renal
• Calculated creatinine clearance > 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
F.1.2.1 Number of subjects for this age ran

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified