Advanced Cancers Harbouring Mutations in HRGPhase 21-2018 BSMONCT03967938
Efficacy of Olaparib in Advanced Cancers Occurring in Patients With Germline Mutations or Somatic Tumor Mutations in Homologous Recombination Genes
A Phase 2 study testing Olaparib Oral Capsule in people with Advanced Cancers Harbouring Mutations in HRG, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancers Harbouring Mutations in HRG
- What is being tested?
- Olaparib Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 540 participants
- Where
- 1 siteBelgium
- Study dates
- 7 Feb 2019to 31 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent prior to any study specific procedures
- Female or male aged > 18 years
- 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)
- No approved targeted therapy for the specific genetic alteration in the specific tumor type
- No other genomic driven phase I, II or III trial available for the specific genomic alteration in the specific tumor type
- Available tumor tissue for verification of the mutation by Sanger sequencing.
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- Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Patients must have a life expectancy ≥16 weeks
- 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.
- Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT and is suitable for repeated assessment.
- *Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be available for local genetic testing.
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Ovarian cancer patients harboring a HRD and breast, prostate and pancreas cancer patients who carry a BRCA1/2 mutation
- Previous enrolment in the present study
- 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.
- History of non-compliance to medical regimens
- Any previous treatment with PARP inhibitor, including olaparib.
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- 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
- 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
- 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.
- 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.
- 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.
- Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) > grade 2) caused by previous cancer therapy, excluding alopecia.
- Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
- 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.
- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
- 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.
- Breast feeding women. (delete if male population)
- Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
- Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Being tested
- Olaparib Oral Capsule
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olaparib Oral CapsuleDrug
Olaparib tablets 300mg twice daily
| Study group | Role | What they receive |
|---|---|---|
| Olaparib | Experimental | tablets of 300mg twice daily until disease progression Receives: Drug: Olaparib Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate according to RECIST 1.1
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.
Measured: 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
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.
Measured: 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 outcomes (3)
locus-specific LOH
Correlate efficacy with locus-specific LOH in the tumors in case of cancers atypical for the germline mutations
Measured: through study completion, an average of 1 year
PFS
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).
Measured: 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
OS is the time from start of treatment until death, for whatever reason.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2019
- Study start7 Feb 2019
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Cancers Harbouring Mutations in HRGStudies of the same condition, open and under way.
- More trials run by Universitair Ziekenhuis BrusselThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 540 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitair Ziekenhuis Brussel
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Kom Op Tegen Kanker
- Responsible party
- Principal investigator, Dr. Sofie Joris, Universitair Ziekenhuis Brussel
- Investigators
- Sofie Joris, Dr, Principal investigator, Universitair Ziekenhuis Brussel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03967938
- Sponsor's protocol ID
- Precision 2 - Olaparib
- Acronym
- 1-2018 BSMO
- Status last verified
- Aug 2024
- First submitted
- 11 Feb 2019
- Last updated
- 19 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Olaparib in Advanced Cancers Occurring in Patients With Germline Mutations or Somatic Tumor Mutations in Homologous Recombination Genes
- ClinicalTrials.gov ID
- NCT03967938
- Acronym / sponsor ID
- 1-2018 BSMO / Precision 2 - Olaparib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 540 participants (estimated)
- Lead sponsor
- Universitair Ziekenhuis BrusselUniversity, hospital or other
- Collaborators
- AstraZeneca, Kom Op Tegen Kanker
- Study start
- 7 Feb 2019 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 30 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olaparib | Experimental | Drug: Olaparib Oral Capsuletablets of 300mg twice daily until disease progression |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Provision of informed consent prior to any study specific procedures
- Female or male aged > 18 years
- 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)
- No approved targeted therapy for the specific genetic alteration in the specific tumor type
- No other genomic driven phase I, II or III trial available for the specific genomic alteration in the specific tumor type
Key exclusion criteria (23 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Ovarian cancer patients harboring a HRD and breast, prostate and pancreas cancer patients who carry a BRCA1/2 mutation
- Previous enrolment in the present study
- 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.
- History of non-compliance to medical regimens
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olaparib Oral CapsuleOlaparib tablets 300mg twice daily | Drug | Olaparib |
Primary outcome
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.
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.
3 secondary outcomes
locus-specific LOH
Time frame: 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.
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2024.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sofie Joris, Dr principal investigator
Universitair Ziekenhuis Brussel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Olaparib Oral Capsule in people with Advanced Cancers Harbouring Mutations in HRG, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2024.