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High Grade Serous CarcinomaPhase 1NCT05358639

Combination of Olaparib and Navitoclax in Women with HGSC and TNBC

A Phase 1 study testing Olaparib tablet and Navitoclax in people with High Grade Serous Carcinoma and Triple Negative Breast Cancer, run by Sunnybrook Health Sciences Centre at 3 sites in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this Phase I study is to determine if the PARP inhibitor olaparib can be safely combined with navitoclax, an inhibitor of Bcl-2/Bcl-XL, in women with TNBC who have somatic or germline mutations in breast cancer gene one (BRCA1) and breast cancer gene two (BRCA2) BRCA1/2 or PALB2 and in women with… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Olaparib tablet and Navitoclax
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
3 sitesCanada
Study dates
9 Nov 2022to 28 Apr 2025
Phase
Phase 1
Are there results?
Not yet: the study is under way

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed:
  • Recurrent metastatic HGSC of ovarian, peritoneal or fallopian tube origin with radiological progression greater than 6 months from last platinum based therapy.
  • Metastatic TNBC: tumors that are known to have deleterious somatic or germline mutations in BRCA1, BRCA2, or PALB2.
  • Age ≥ 18 years of age.
  • ECOG Performance Status of 0, 1 or 2 within 7 days prior to registration (Appendix 4).
  • No more than two (2) prior lines of treatment for TNBC.
Show all 14Show fewer
  • No limit on the number of prior lines for HGSC.
  • Prior maintenance or treatment with PARP inhibitor is allowed provided progression did not occur on or within 6 months of discontinuing the drug. Patients must be considered able to tolerate olaparib as per dosing regimen in this study.
  • Patients must be able to swallow and retain oral medications and without gastrointestinal illnesses that would preclude absorption.
  • Patients must be able and willing to undergo study related procedures (biopsies pre and on treatment) and to provide archival tissue, if available.
  • Patients must have a life expectancy ≥16 weeks.
  • Patients must have adequate organ and marrow function measured within 28 days prior to administration of study drug
  • Patients must have measurable disease as defined by RECIST 1.1. Progressive irradiated lesions considered but would require an additional out of field measurable lesion.
  • 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.

Who cannot join

  • Prior chemotherapy, endocrine therapy, radiotherapy, or investigational agents within 30 days prior to first dose of investigational products (IPs).
  • Due to the expected dose-limiting toxicity of thrombocytopenia, the following concomitant medications are not allowed within 14 days of the olaparib lead-in period: Warfarin, clopidogrel (plavix), ibuprofen, tirofiban (aggrastat), and other anticoagulants drugs including low molecular weight heparin, or herbal supplements that affect platelet function are excluded. Caution should be exercised when dosing Navitoclax concurrently with CYP2C8 and CYP2C9 substrates.
  • Due to the known effects of navitoclax on platelet counts, patients with active bleeding or thrombocytopenia-associated bleeding within 1 year, active peptic ulcer disease or potentially hemorrhagic esophagitis or gastritis, a requirement for concurrent therapeutic anticoagulants, or a history of immune thrombocytopenic purpura, autoimmune hemolytic anemia, or refractoriness to platelet transfusions.

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

  • CHUM

    Montreal, Quebec, H2X 0A9

  • Sunnybrook Research Institute/Odette Cancer Centre

    Toronto, Ontario, M4N 3M5

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 1Z5

Other trials in Canada

About this study

Official title: A Phase I Trial of the Combination of Olaparib and Navitoclax in Women with High Grade Serous Epithelial Ovarian Cancer and Triple Negative Breast Cancer

The purpose of this Phase I study is to determine if the PARP inhibitor olaparib can be safely combined with navitoclax, an inhibitor of Bcl-2/Bcl-XL, in women with TNBC who have somatic or germline mutations in breast cancer gene one (BRCA1) and breast cancer gene two (BRCA2) BRCA1/2 or PALB2 and in women with recurrent HGSC who have progressed greater than 6 months since their last platinum containing chemotherapy. The trial is designed as an open- label multi-center Phase I interventional and translational study. It will identify the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D of olaparib combined with navitoclax for study in Phase II. There is a plan for a follow on Phase II study depending on the results obtained during this Phase I trial.The rationale for this study is that for a subset of patients, olaparib, will increase tumor cell survival dependence on inhibition of cell death by Bcl 2/Bcl- XL. Thus, navitoclax will augment apoptosis induced by PARP inhibition with olaparib.

Read the detailed description

In this trial, olaparib will be delivered alone for 14 days with the hypothesis that priming of the apoptotic machinery will be required prior to introduction of the senolytic agent (navitoclax). To date navitoclax and olaparib have not been combined in the clinic. The Phase I study will therefore be conducted to define the recommended Phase II dose (RP2D). A plan for a future Phase II study will depend on the results obtained during this Phase I trial. Based on the potential for overlapping toxicity (particularly hematologic toxicity) an interrupted dosing schedule will be used for the navitoclax. Based on preclinical studies it is believed that intermittent delivery of the senolytic agent is in line with the proposed mechanism of action. Subsequently the dose of navitoclax will be escalated with a fixed dose of olaparib in 28-day cycles.

Being tested
Olaparib tablet, Navitoclax
Keywords
BRCA1 Mutation, BRCA2 Mutation, PALB2 Gene Mutation, Olaparib, Navitoclax, Bcl-2, Bcl-xL, Bax, Mcl-1, Bcl-W, Bak, Bok, Bid, Bim, Bad, Bik, Noxa, Puma
Medical subject headings
Triple Negative Breast Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Olaparib tabletDrug

    Also called Lynparza

    Olaparib tablet will be administered alone for 14 days at a starting dose of 200 mg twice daily. Subsequently olaparib will be administered continuously over 28 days at a fixed dose and the dose of navitoclax will be escalated.

  • NavitoclaxDrug

    Also called ABT-263

    For navitoclax, a lead-in of 7 days at 150 mg PO will be used prior to dose escalation. The DLT period for dose levels above DL 3 will include the 14-day olaparib alone lead-in, the 7 days combination with navitoclax at 150 mg and the first 28 day cycle of the combination of olaparib and navitoclax cycle at the full dose level dosing (49 days).

Study groups in NCT05358639
Study groupRoleWhat they receive
SingleExperimentalOlaparib tablet will be administered alone for 14 days at a starting dose of 200 mg twice daily (bid). Subsequently olaparib will be administered continuously over 28 days at a fixed dose and the dose of navitoclax will be escalated. Navitoclax will be administered daily. The initial dose of olaparib 200 mg has been selected after considering the single agent Phase I/II dose based and on ongoing combination studies on expected toxicity and evidence for reduced PARP inhibition
Receives: Drug: Olaparib tablet; Drug: Navitoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To define a dose and schedule of navitoclax (Recommended Phase II Dose, RP2D) that can be combined safely with Olaparib in women with metastatic recurrent high grade serous ovarian cancer (HGSC) and triple negative breast cancer (TNBC) for further study

    The RP2D will be determined based on an evaluation of multiple endpoints, which will include the DLT( dose limiting toxicity) rate.

    Measured: 2 years

Secondary outcomes (2)

  1. Cmax: the maximum drug concentration.

    The maximum drug concentration will be measured in blood samples as part of the PK profile of olaparib and navitoclax when given in combination.

    Measured: 2 years

  2. Tmax: time to reach the maximum drug concentration.

    The time to reach maximum drug concentration will be measured in blood samples as part of the PK profile of olaparib and navitoclax when given in combination.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2022
  2. Study start9 Nov 2022
  3. Primary completion30 Mar 2025 (estimated)
  4. Study completion28 Apr 2025 (estimated)

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
The trial is designed as an open-label multi-center Phase I interventional and translational study. It will identify the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D of olaparib combined with navitoclax for study in Phase II.
Masking
None (open label)
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05358639
Sponsor's protocol ID
Exactis-03
Status last verified
Nov 2024
First submitted
22 Mar 2022
Last updated
18 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Olaparib tablet and Navitoclax in people with High Grade Serous Carcinoma and Triple Negative Breast Cancer, run by Sunnybrook Health Sciences Centre at 3 sites in Canada.

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 14 inclusion and 3 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: under way, not looking for participants, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

To define a dose and schedule of navitoclax (Recommended Phase II Dose, RP2D) that can be combined safely with Olaparib in women with metastatic recurrent high grade serous ovarian cancer (HGSC) and triple negative breast cancer (TNBC) for further study (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05358639.

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 18 Nov 2024.

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