None listed
Conditions
Brief summary
The REPURPOSE Trial aims to assess the efficacy and safety of oral efavirenz in high grade serous ovarian, fallopian tube and primary peritoneal cancer. Who is it for? You may be eligible for this study if you are an adult female with platinum resistant or potentially platinum sensitive high grade serous ovarian, fallopian tube and primary peritoneal cancer. Study details All participants will receive daily oral efavirenz (600mg) for 24 months or until disease progression by RECIST 1.1 or CA125 GCIG criteria unless the clinician believes that there is a clinical benefit to continue treatment beyond progression and there is no unacceptable toxicity resulting from the treatment. Data will be collected on clinical response and incidence of adverse events. It is hoped that findings from this study will inform researchers and clinicians of the role of efavirenz in the landscape of gynaecological cancer treatment.
Interventions
Daily oral efavirenz (600mg) for 24 months or until disease progression by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.) or CA125 Gynecologic Cancer Intergroup (GCIG) criteria unless the clinician believes that there is a clinical benefit to continue treatment beyond progression and there is no unacceptable toxicity resulting from the treatment.
Plasma concentration of efavirenz will be measured at weeks 1, 4 and 18.
Pharmacy Logs will record number of tablets dispensed and re
Daily oral efavirenz (600mg) for 24 months or until disease progression by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.) or CA125 Gynecologic Cancer Intergroup (GCIG) criteria unless the clinician believes that there is a clinical benefit to continue treatment beyond progression and there is no unacceptable toxicity resulting from the treatment. Plasma concentration of efavirenz will be measured at weeks 1, 4 and 18. Pharmacy Logs will record number of tablets dispensed and returned by each participant
Sponsors
The University of Newcastle
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Written informed consent to participate in the trial must be given according to International Council for Harmonisation's (ICH) Good Clinical Practice guidelines (GCP) and national/local regulations • Histologically confirmed high grade serous carcinoma of the ovary, fallopian tube or primary peritoneal carcinoma • Female subjects >= 18 years • Measurable disease by RECIST 1.1 criteria or in patients without measurable disease, evaluable disease by GCIG CA125 criteria (Patients can be evaluated according to CA125 only if they have a pretreatment CA125 level that is at least twice the upper limit of normal within 2 weeks prior to starting treatment). • Platinum resistant disease defined as progressive disease by imaging >6 months from the last date of most recent platinum-based chemotherapy. • Potentially platinum sensitive disease (defined as >6 months from last date of most recent platinum-based chemotherapy) will be allowed if subjects have received a minimum of 3 lines of platinum based chemotherapy • Prior exposure to bevacizumab, parp inhibitors, antibody-drug conjugates and immune checkpoint inhibitors and other investigation agents is allowed but not required for participation • At least 21 days since completion of prior therapy including chemotherapy, major surgery and other investigational agents. • Resolution of all prior treatment toxicities to grade 1 or less (excluding alopecia) • Haemoglobin >10g/dL (packed red cell infusion allowed) • Absolute neutrophil count >1.0 x109/L, Platelets >75 x 109/L, Total bilirubin <1.5 x upper limit of normal (ULN) except in patients with known Gilbert’s syndrome, Aspartate transaminase (AST) and alanine transaminase (ALT) <3 x ULN , or 50mL/min according to Cockroft Gault formula or local institutional method. • Eastern Cooperative Oncology Group (ECOG) Performance status 0 -2 • Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first dose of study treatment
Exclusion criteria
• Primary platinum refractory disease defined as progression during or within one month of completion of prior platinum therapy. • Current uncontrolled psychiatric illness; OR • A new diagnosis of major psychiatric illness in the past two years (see list below) - Bipolar disorder; - Post-traumatic Stress Disorder (PTSD); - Borderline personality disorder; - History of severe major depression with suicidal ideation • Known CNS metastases (including brain or leptomeningeal) • Coadministration of drugs interacting with efavirenz (including midazolam, voriconazole and cisapride. Full list of prohibited medications in Appendix A) • Prior organ transplantation, including allogeneic stem-cell transplantation • Diagnosis of HIV; positive test for active hepatitis B or hepatitis C or any other significant acute or chronic infections • Patient currently participating or receiving any systemic study therapy or participating in a study of a systemic investigational agent and received study therapy or used an investigational device within 3 weeks prior to the first dose of treatment • Significant cardiovascular disease defined as: uncontrolled hypertension/angina/heart failure/arrhythmias that require a significant change in systemic treatment within the past 3 months to stabilize the cardiovascular disease. • History of prolonged QTc or Torsades de Pointes or baseline prolonged QTcB (>/= 450msec) on screening ECG • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
Outcome results
None listed