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

Ovarian Cancer Clinical Trial

— NEO  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02489006
• Other study ID #: OZM-058
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 19, 2016
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2024
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 71
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Debulking Surgical Procedures
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Neoadjuvant Treatment
• Ovarian Cancer

Intervention

Drug:
• Olaparib

• Platinum-based Chemotherapy
Chosen by the study doctor, per standard of care.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Centre hospitalier de l'Université de Montréal (CHUM	Montréal	Quebec
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
New Zealand	Auckland City Hospital	Grafton	Auckland
Spain	Vall d'Hebron University Hospital	Barcelona
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	Royal Marsden Hospital NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Countries where clinical trial is conducted

Canada,  New Zealand,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in levels of PAR or PARP-1 before and after study treatment		4-8 weeks
Primary	Mutations in BRCA1/2, RAD51B, RAD51C, RAD51D, PPM1D, FANCM, BRIP1, PALB2 and BARD1 in germline tissue compared to tumor tissue		2.5 years
Secondary	Frequency of adverse events, by description and grade		2.5 years
Secondary	Response rate to olaparib in the neoadjuvant period		6 weeks
Secondary	Duration of progression free survival with olaparib in comparison to platinum based chemotherapy		2.5 years
Secondary	Levels of ctDNA compared to levels of CA125		2.5 years
Secondary	Gene expression changes in tumour tissue before and after treatment with Olaparib		2.5 years
Secondary	Secondary mutation rate in surgical tumour specimens following PARP therapy and at progression	2.5 years	2.5 years
Secondary	Changes in blood based biomarkers using ctDNA before, during and after treatment with Olaparib		2.5 years