A Study of Olaparib Prior to Surgery and Chemotherapy in Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (NEO)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Neoadjuvant Treatment; Debulking Surgical Procedures
• Intervention / Treatment: Drug: Olaparib; Drug: Platinum-based Chemotherapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Regional Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada, H2L 2W5
      • Centre hospitalier de l'Université de Montréal (CHUM
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand
      • Auckland City Hospital
• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron University Hospital
• United Kingdom
  • London, United Kingdom
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation.
• Ability to understand and the willingness to sign a written informed consent document.
• Subject's willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

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
• Other anti-cancer therapy including immunotherapy, hormonal therapy, biological therapy, other novel agents or investigational agents
• Persistent toxicities (CTCAE v 4.03 grade >2) caused by previous cancer therapy, excluding alopecia
• Patients with myelodysplastic syndrome/acute myeloid leukemia
• Patients with brain metastases
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
• Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
• Pregnant or breastfeeding women
• Receipt of live attenuated vaccine within 30 days prior to enrollment
• Patients with > Grade 2 hearing impairment as per CTCAE v 4.03
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Olaparib; Other Names: Lynparza; Drug: Platinum-based Chemotherapy; Chosen by the study doctor, per standard of care.
Experimental: 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.	Drug: Olaparib; Other Names: Lynparza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in levels of PAR or PARP-1 before and after study treatment	4-8 weeks
Mutations in BRCA1/2, RAD51B, RAD51C, RAD51D, PPM1D, FANCM, BRIP1, PALB2 and BARD1 in germline tissue compared to tumor tissue	2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	2.5 years
Changes in blood based biomarkers using ctDNA before, during and after treatment with Olaparib		2.5 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Amit Oza, M.D., Princess Margaret Cancer Centre/University Health Network

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2016
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: April 17, 2015
• First Submitted That Met QC Criteria: June 30, 2015
• First Posted (Estimated): July 2, 2015

Study Record Updates

• Last Update Posted (Estimated): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 14, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Adnexal Diseases; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Fallopian Tube Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib
• Other Study ID Numbers: OZM-058