A Phase II, Open-Label, Randomized, Multi-Centre Study, of Neoadjuvant Olaparib in Patients With Platinum Sensitive Recurrent High Grade Serous Ovarian/Primary Peritoneal or Fallopian Tube Cancer
Overview
- Phase
- Phase 2
- Intervention
- Olaparib
- Conditions
- Ovarian Cancer
- Sponsor
- University Health Network, Toronto
- Enrollment
- 71
- Locations
- 9
- Primary Endpoint
- Difference in levels of PAR or PARP-1 before and after study treatment
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a study that will look at the effects and how useful investigational drug olaparib is as a neoadjuvant treatment (treatment given as to shrink a tumor before the main treatment) prior to surgery in patients with recurrent ovarian, primary peritoneal or fallopian tube cancer.
Detailed Description
Olaparib belongs to a class of anti-cancer agents known as poly ADP-ribose polymerase (PARP) inhibitors. Olaparib is a new type of drug for ovarian cancer. Laboratory tests show that it may help slow the growth of ovarian cancer. Olaparib works by blocking the PARP protein. PARP is an important protein which tries to fix damaged deoxyribonucleic acid (DNA, molecules that contain important instructions for the development of cells). Many cancers are thought to develop from damaged DNA. Research has shown that PARP inhibitors stop the PARP protein from working, and that sometimes that can cause cancer cells to stop growing or die.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically proven recurrent high grade serous ovarian/primary peritoneal or fallopian tube cancer.
- •Patients must have disease amenable to pre-operative biopsy.
- •Patients must have disease deemed suitable for surgical debulking.
- •Patients must have a progression free interval of at least 6 months prior to registration.
- •Patients must have had at least one line of platinum based therapy.
- •Patients must have shown platinum sensitivity to their last line of platinum therapy
- •Age \>=18 years
- •ECOG performance status 0-1 within 7 days of registration
- •Life expectancy of greater than 3 months
- •Patients must have normal organ and marrow function
Exclusion Criteria
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib.
- •History of allergic reactions attributed to platinum precluding further use.
- •Radiation therapy within 4 weeks of registration
- •Use of any other systemic, targeted, immunotherapy, chemotherapy, or investigational agents within 4 weeks of registration
- •Previously received a PARP inhibitor
- •Other malignancy within the last 2 years with exceptions
- •Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
- •Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
- •Concomitant use of known potent CYP3A4 inhibitors
- •Concomitant use of known potent CYP3A4 inducers
Arms & Interventions
Olaparib Prior to Surgery, Chemotherapy/Olaparib Post Surgery
Olaparib, orally, at 300 mg twice per day, for 6 weeks (+/- 2 weeks) prior to surgery. Platinum-based chemotherapy chosen by the study doctor and per standard of care after surgery. Olaparib, orally, at 300 mg twice per day, continuously, after chemotherapy.
Intervention: Olaparib
Olaparib Prior to Surgery, Chemotherapy/Olaparib Post Surgery
Olaparib, orally, at 300 mg twice per day, for 6 weeks (+/- 2 weeks) prior to surgery. Platinum-based chemotherapy chosen by the study doctor and per standard of care after surgery. Olaparib, orally, at 300 mg twice per day, continuously, after chemotherapy.
Intervention: Platinum-based Chemotherapy
Olaparib Prior to Surgery and Post Surgery
Olaparib, orally, at 300 mg twice per day, for 6 weeks (+/- 2 weeks) prior to surgery and after surgery.
Intervention: Olaparib
Outcomes
Primary Outcomes
Difference in levels of PAR or PARP-1 before and after study treatment
Time Frame: 4-8 weeks
Mutations in BRCA1/2, RAD51B, RAD51C, RAD51D, PPM1D, FANCM, BRIP1, PALB2 and BARD1 in germline tissue compared to tumor tissue
Time Frame: 2.5 years
Secondary Outcomes
- Frequency of adverse events, by description and grade(2.5 years)
- Response rate to olaparib in the neoadjuvant period(6 weeks)
- Duration of progression free survival with olaparib in comparison to platinum based chemotherapy(2.5 years)
- Levels of ctDNA compared to levels of CA125(2.5 years)
- Gene expression changes in tumour tissue before and after treatment with Olaparib(2.5 years)
- Secondary mutation rate in surgical tumour specimens following PARP therapy and at progression(2.5 years)
- Changes in blood based biomarkers using ctDNA before, during and after treatment with Olaparib(2.5 years)