STICs and STONES: OV.24 A randomized phase II double-blind - - PowerPoint PPT Presentation

STICs and STONES: OV.24 A randomized phase II double-blind placebo-controlled trial of Acetylsalicylic acid (ASA) in chemoprevention of ovarian cancer in women with BRCA1/2 mutations/Group name and number

Co Chairs: Oza A – Lheureux S Pathology Chair: Patricia Shaw Senior Investigator: Wendy Parulekar Statistician: Dongsheng Tu Study coordinator: WenLing Liu Sponsor: CCTG Grant Support: CCSRI: Hecht Foundation: CCTG: PM Cancer Foundation: Drug Supply: Apotex GCIG Groups: ANZGOG: K. Phillips ISGO: J. Korach, D. Tsoref NCRI: R. Manchanda

Stratification

• Age (<40 vs 40-50 vs >50)
• Current (last dose <6 mths) combined oral

contraceptive use (Yes vs No)

• BRCA status (BRCA1 vs BRCA2)

OV.24 / CCTG

Trial setting: Women with germline BRCA1/2 mutations scheduled to undergo risk reducing surgery within 6 months to 2 years Study Design: Randomized 2:1, double-blind, placebo controlled phase II Sponsor(s): CCTG, ANZGOG Planned No. of patients: 414 Current accrual: Commencing Fall 2017 in Canada and Australia Other important information: Study has been submitted to Health Canada as pre-Clinical Trials Application. Pending further communication with regulatory authorities Ongoing Trials – status update

A phase II, open-label, randomized, multi-centre study

• f neoadjuvant olaparib in ovarian cancer (NEO Trial)

PIs: Oza AM & Brenton J. Sponsor: PMHC Grant Support: Investigator-initiated, AstraZeneca Global GCIG Groups: Belgium, Italy, New Zealand, and United Kingdom

Platinum sensitive HGSOC Olaparib Surgery 6 cycles platinum-based chemotherapy Maintenance Olaparib

Olaparib Biopsy* Biopsy* On progression

ctDNA weekly ctDNA pre each cycle CT CT# CT CT every 9 weeks R

NEO / PMHC

Trial setting: Platinum Sensitive Recurrent High Grade Serous Ovarian/Primary Peritoneal or Fallopian tube Cancer Study Design: Phase II, randomized, open-label Sponsor(s): PMHC Planned No. of patients: 75 Current accrual: 5 enrolled, 1 in screening Other important information: If positive signal, study will expand to N=150. Correlatives include: ctDNA; BRCA1/2 and HRD analysis; PARP expression; serial biopsy sites to examine heterogeneity of disease; at each biopsy time point ascitic fluid collection (where applicable). Ongoing Trials – status update

A proof of concept, multi-centre, clinical trial of the combination cediranib-olaparib at the time of disease progression on PARP inhibitor in ovarian cancer eVOLVE/PMHC Ongoing Trials – status update

PIs: Oza AM Sponsor: PMHC Grant Support: Investigator-initiated, AstraZeneca Global Previous therapy PARP inhibitor >6 months Cediranib/Olaparib Orally daily

Proof of concept study

Progression

• n PARP

If signal detected, trial continue to randomized phase 2 setting

• A total of 30 patients with ovarian cancer who progressed
• n any PARP inhibitor that meet one of the following

criteria:

– Cohort of 10 platinum sensitive with no evidence of disease progression within 6 months of the last dose of platinum based chemotherapy and received PARP as their last line of treatment – Cohort of 10 platinum resistant with disease progression within 6 months of the last dose of a platinum based chemotherapy and received PARP inhibitor as their last line of treatment – Exploratory cohort of 10 patients who had progressed on PARP and then received standard chemotherapy with further disease progression

eVOLVE/PMHC Ongoing Trials – status update

eVOLVE/PMHC Trial setting: Recurrent high grade serous ovarian cancer Study Design: A multi centre, open-label, proof of concept study investigating the combination cediranib-olaparib at the time of disease progression on PARP inhibitor in

• varian cancer.

Sponsor(s): PMHC Planned No. of patients: 31 Current accrual: 16 Other important information: Any prior PARP treatment allowed; platinum sensitive, resistant and exploratory cohorts; ctDNA analysis; archival tissue and up to 3 fresh core biopsies at the time of entry, and time of progression; germline BRCA1/2; PG analysis. Ongoing Trials – status update

SUPPLEMENTAL SLIDES

OV.24 / CCTG

Stratification

• Age (<40 vs 40-50 vs >50)
• Current (last dose <6 mths) combined oral contraceptive use (Yes vs No)
• BRCA status (BRCA1 vs BRCA2)

Ongoing Trials – status update

• Secondary

– To assess Patient Acceptance of Intervention of Chemoprevention Studies in this High-risk Female Cohort

• Tertiary

– To characterize the Effect of Aspirin on HGSOC Tumourigenesis

• Link between Tumourigenesis and Microenvironment

– Hormone stimulation – Inflammatory cell phenotype – Markers of inflammation and oncogenic pathway expression

• Biobanking for future correlative studies

OV.24 / CCTG

Ongoing Trials – status update