Clinical trial NCT02489058: A Study of Long-Term Responders on Olaparib
Official title: A Retrospective/Prospective Analysis of Characterization of the Long-Term Responders on Olaparib in Solid Tumours
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Epithelial Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2015-07-02
Enrollment: 118
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Epithelial ovarian cancer (including fallopian tube or peritoneal cancer) patients that are or had received treatment with Olaparib.

Brief summary: This is an observational and sample collection study involving patients (alive or deceased) from several clinical trials who had received the investigational drug, olaparib in other research studies. There is no intervention given for this study.

This research is being done to understand of the mechanisms involved in patients whose cancer responds well and whose cancer does not respond well to investigational drug, olaparib, to help better understand how olaparib works and to better identify patients who may benefit from this therapy.

Detailed description: This is study will compare biomarker research with response in patients who have received olaparib.

Patients who have had a durable response to olaparib for at least 2 years will be approached for the study.

Patients who agree to this study will then have their medical history collected and will be asked to complete a questionnaire. Archival tumor tissue will also be collected for biomarker research.

A waiver of consent is requested to access the medical records and archival tumor tissue of patients who are deceased.

If participants are still taking olaparib, they will be asked to provide blood samples for pharmacokinetics and circulating tumor DNA, and the results of CT scans taken as part of their standard of care or as a part of another research study. If participants' disease worsens while still on olaparib, they will then be asked to provide a blood sample for pharmacogenomics and BRCA testing (if not known). An optional tumor biopsy will also be requested.

Participants will continue to be followed by telephone for survival and any new treatments they are receiving.

Eligibility criteria: Inclusion Criteria:

* Previous or current treatment with Olaparib in a clinical trial/standard of care that included one of the following as a first step study for epithelial ovarian cancer (including fallopian tube or peritoneal cancer):

  * single agent olaparib given for relapsed disease or
  * single agent olaparib given as maintenance therapy after response to platinum based chemotherapy or
  * olaparib combined with platinum based chemotherapy and then continued as maintenance therapy or
  * olaparib combined with other types of therapy
* Had a durable response to Olaparib defined as patients who have benefited from olaparib for \> 18 months. Patients who discontinued Olaparib due to toxicities but otherwise meet the definition of a durable response will be included or the control group is patients who had a short duration benefit with Olaparib of less than 6 months in any individual clinical trial/standard of care
* Ability to understand and the willingness to sign a written informed consent document.
* Patient's willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures.

Exclusion Criteria:

* Any severe acute or chronic medical or psychiatric condition or laboratory abnormality that would render the patient unsuitable for biopsy
* Pregnant or breastfeeding women

Primary outcomes:
measure: The number of patients with somatic BRCA mutations compared to number of patients without somatic BRCA mutations
timeFrame: 4 years
measure: The number of patients with homologous recombination repair deficiencies compared to the number of patients that do not have homologous recombination repair deficiencies.
timeFrame: 4 years
measure: The number and types of mutated genes.
timeFrame: 4 years
measure: The number of patients with antibodies to the study drug
timeFrame: 4 years
measure: Evaluate the levels of PI3K/Akt pathway expression per patient
timeFrame: 4 years
Secondary outcomes:
measure: HRR deficiency profile
timeFrame: 4 years
measure: Level of poly (ADP-ribose) (PAR) expression
timeFrame: 4 years
measure: Signature of PARP response compared with signature of platinum sensitivity
timeFrame: 4 years
measure: Signature of PARP response and PARP resistance on different tumour sites
timeFrame: 4 years
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: South Eastern Sydney Local Health District
state: New South Wales
city: Vancouver
country: Canada
facility: British Columbia Cancer Centre
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Milan
country: Italy
facility: Institute of European Oncology
city: Barcelona
country: Spain
facility: Vall d'Hebron
city: Sutton
country: United Kingdom
facility: The Royal Marsden
state: England
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Research Centre
state: Scotland
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Amit Oza, M.D.
role: PRINCIPAL_INVESTIGATOR
References: