Efficacy of Olaparib in Advanced Cancers Occurring in Patients With Germline Mutations or Somatic Tumor Mutations in Homologous Recombination Genes (1-2018 BSMO)

August 16, 2024 updated by: Dr. Sofie Joris, AZ-VUB
At present targeted therapy with the PARP inhibitor olaparib has become standard of care in advanced platinum sensitive BRCA1/2 mutant ovarian cancer. The key in this sensitivity is the loss of homologous recombination (HR) function. The current project aims to treat patients with any type of cancer carrying in their germline a mutation in genes that generate such an homologous recombination deficiency (HRD) or have an acquired somatic mutation in their tumor with the targeted PARP inhibitor olaparib. The project would thus bring access to a targeted drug matched to the genomic profile of the tumor of these patients and provide oncologists with information regarding efficacy and safety of olaparib in these patients. This evidence could then later lead to a more routine regulatory access.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
540

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Belgium
      • Brussels, Belgium, 1090
        • UZ Brussel

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Provision of informed consent prior to any study specific procedures
  2. Female or male aged > 18 years
  3. Histologically proven advanced cancer, either locally or metastatic, harboring a specific pathogenic genetic alteration (with the exception of breast, pancreas, or prostate cancer patients harboring a BRCA1/2 mutation and HRD ovarian cancer)
  4. No approved targeted therapy for the specific genetic alteration in the specific tumor type
  5. No other genomic driven phase I, II or III trial available for the specific genomic alteration in the specific tumor type
  6. Available tumor tissue for verification of the mutation by Sanger sequencing.
  7. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment.
  8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  9. Patients must have a life expectancy ≥16 weeks
  10. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
  11. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
  12. At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT and is suitable for repeated assessment.
  13. *Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be available for local genetic testing.

Exclusion Criteria:

  1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
  2. Ovarian cancer patients harboring a HRD and breast, prostate and pancreas cancer patients who carry a BRCA1/2 mutation
  3. Previous enrolment in the present study
  4. Participation in another clinical study with an investigational product during the last 4 weeks or radiotherapy (except for palliative reasons) within three weeks prior to study treatment.
  5. History of non-compliance to medical regimens
  6. Any previous treatment with PARP inhibitor, including olaparib.
  7. Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years. Patients with a history of localized triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
  8. Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or indicating uncontrolled, potentially reversible cardiac conditions as judged by the investigator (er., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500ms, electrolyte disturbances, etc.) or patients with congenital long QT syndrome
  9. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within four weeks prior to study treatment. Patients must have recovered from radiotherapy toxicities prior to enrollment.
  10. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
  11. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  12. Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) > grade 2) caused by previous cancer therapy, excluding alopecia.
  13. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
  14. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
  15. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
  16. 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.
  17. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  18. Breast feeding women. (delete if male population)
  19. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
  20. Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
  21. Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
  22. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
  23. Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable, for timing refer to inclusion criteria no.3)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Olaparib
tablets of 300mg twice daily until disease progression
Drug: Olaparib Oral Capsule
Olaparib tablets 300mg twice daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Response rate according to RECIST 1.1
Time Frame: every 2 months from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
The primary analysis will estimate the proportion of patients who achieve confirmed objective response according to the RECIST criteria. Objective response is defined as confirmed CR or PR.
every 2 months from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Response duration according to RECIST 1.1
Time Frame: from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Patients whose best RECIST assessment is stable disease, partial, or complete response will be considered to have achieved disease control. Descriptive statistics will be produced for the duration of confirmed objective response and disease control.
from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
locus-specific LOH
Time Frame: through study completion, an average of 1 year
Correlate efficacy with locus-specific LOH in the tumors in case of cancers atypical for the germline mutations
through study completion, an average of 1 year
PFS
Time Frame: every 2 months from date of randomization until teh date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.
PFS is the time from start of treatment until the occurrence of disease progression or death, whichever comes first. Date of progression is the earliest of (1) date of imaging showing disease progression, or (2) date of investigator assessment of clinical progression, or (3) date recorded from post study follow-up for disease progression, or (4) start of new anti-cancer treatment (i.e., either the secondary treatment regimen or other anti-cancer treatment).
every 2 months from date of randomization until teh date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.
OS
Time Frame: every 2 months from date of randomization until teh date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.
OS is the time from start of treatment until death, for whatever reason.
every 2 months from date of randomization until teh date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AZ-VUB

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
AstraZeneca
Kom Op Tegen Kanker

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sofie Joris, Dr, Universitair Ziekenhuis Brussel

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 7, 2019

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 11, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 30, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 19, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Precision 2 - Olaparib

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings