NEoadjuvant Olaparib Combination OvArian Cancer Targeted Study

NCT06650709 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: OZM-136
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this phase 2 clinical trial is to learn if the three treatments olaparib, durvalumab and bevacizumab can treat participants with a diagnosis of stage 4 high grade serous ovarian cancer that is too advanced to undergo upfront surgery. The main questions it aims to answer are: Is the treatment able to shrink the cancer sufficiently for participants to undergo surgery? Is the combination of treatments safe in this neoadjuvant (before surgery) setting? This is a single arm study with no comparator arm. Participants will receive the treatment up to 3 cycles with each drug given as follows in a 28-day cycle: Olaparib orally on a twice daily continuous dosing schedule Durvalumab given intravenously on day 1 Bevacizumab given intravenously on day 1 and 15 (Day 15 omitted in C3) Participants will be assessed throughout the study for safety and efficacy endpoints

Conditions

Ovarian Cancer Stage IV

Outcome Measures

Primary Outcomes (1)

• To determine the efficacy of the triplet combination Olaparib-Durvalumab-Bevacizumab in the neoadjuvant setting in subjects with FIGO Stage IV high grade serous ovarian cancer.

  Objective Response Rate (complete response (CR) + partial response (PR)) at 8 weeks based on RECIST 1.1. as assessed by the Investigator.

  Approximately 3 years, including 1 year of recruitment, 6 months treatment period, and 1 year of follow-up

Study Arms (1)

Olaparib-Durvalumab-Bevacizumab

EXPERIMENTAL

Olaparib 300mg PO BID continuous dosing, Durvalumab 1500mg IV Day 1, Bevacizumab 10mg/kg IV Day 1 and 15 of a 28-day cycle Patients that respond to the therapy following 2 cycles will receive a 1 further cycle with the C3 Day 15 Bevacizumab omitted.

Drug: Olaparib; Drug: Bevacizumab; Drug: Durvalumab

Interventions

Olaparib DRUG

Olaparib 300mg orally twice daily on a continuous dosing schedule for a maximum of 3 x 28-day cycles.

Olaparib-Durvalumab-Bevacizumab

Bevacizumab DRUG

Bevacizumab 10mg/kg intravenously on Day 1 and 15 of the 28 day cycle for a maximum of 3 cycles (Cycle 3, Day 15 will be omitted).

Also known as: biosimilar

Olaparib-Durvalumab-Bevacizumab

Durvalumab DRUG

Durvalumab 1500mg intravenously on Day 1 of the 28 day cycle for a maximum of 3 cycles.

Olaparib-Durvalumab-Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
• Histologically proven high grade serous ovarian/ fallopian tube or primary peritoneal cancer.
• Chemotherapy naïve for high grade serous ovarian/ fallopian tube or primary peritoneal cancer.
• FIGO Stage IVA/B disease not suitable for primary debulking surgery but must have the intention of proceeding to interval surgical debulking if treatment response is demonstrated
• Patients must have disease amenable to pre-operative screening biopsies for additional translational endpoints or availability of sufficient archival tissue for additional translational endpoints including HRR pathway testing.
• At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (or magnetic resonance imaging \[MRI\] where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1. The baseline scan must be obtained within 28 days prior to the first dose of study treatment.
• Age ≥18 years.
• Body weight \>30 kg
• ECOG performance status 0-1 within 7 days of study registration.
• Life expectancy of \> 4 months.
• Normal organ and bone marrow function within 14 days prior to first dose, including:
• Platelets ≥100x109/L
• Hemoglobin ≥10 g/dL with no blood transfusion in the past 28 days
• ANC ≥ 1.5 X 109/L
• Total bilirubin ≤1.5 x upper limit of normal (ULN) unless due to Gilbert's syndrome

You may not qualify if:

• Known germline BRCA1/2 mutation carriers or known somatic BRCA1/2 mutation associated HGSOC (prior to screening)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the Triplet Combination (olaparib, durvalumab, bevacizumab).
• Use of any other anti-cancer therapy including systemic, targeted, immunotherapy, hormonal, biological, chemotherapy, other novel agents or investigational agents within 4 weeks of registration.
• Participation in another clinical trial with an investigational product within 4 weeks of registration
• Previous treatment with an immune checkpoint inhibitor, including durvalumab study regardless of treatment arm assignment
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Previously received a PARP/VEGF/PD/L-1/CTLA4 targeted therapy for this cancer diagnosis or any other cancer diagnosis in the last 5 years.
• Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4:
• Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
• Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
• Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day.
• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal breast carcinoma in situ, Stage 1, grade 1 endometrial carcinoma, or other solid tumors (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• AstraZeneca: collaborator
• Ozmosis Research Inc.: collaborator

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

olaparib; Bevacizumab; Biosimilar Pharmaceuticals; durvalumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Central Study Contacts

Yvette Drew, PhD, MD

CONTACT

1-6048776000; yvette.drew@bccancer.bc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm, open label study.

Study Record Dates

• First Submitted: October 18, 2024
• First Posted: October 21, 2024
• Study Start: November 1, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): November 1, 2028
• Last Updated: October 23, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Immediately following final publication. No end date.