Breast CancerPhase 2OTT-19-06NCT04676516
A Phase II Window of Opportunity Trial of PRMT5 Inhibitor, GSK3326595, in Early Stage Breast Cancer
A Phase 2 study testing GSK3326595 in people with Breast Cancer, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
This is a Phase II Randomized Window of Opportunity Trial Evaluating Clinical and Biological effects of PRMT5 inhibitor, GSK3326595, in Early Stage Breast Cancer Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- GSK3326595
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- 8 Jun 2021to 15 Aug 2022
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients with newly diagnosed histologically confirmed primary invasive breast cancer currently not undergoing any treatment while awaiting surgery
- Operable breast cancer as assessed by treating surgical oncologist
- Tumor ≥ 1.0 cm by palpation or imaging
- ER or PR positive (≥1%) breast adenocarcinoma
- Her2 negative as per ASCO 2018 guidelines 61
- Invasive ductal or lobular carcinoma, invasive carcinoma Not Otherwise Specified (NOS)
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- ECOG PS 0-2 (Appendix A)
- Post-menopausal and not of child bearing potential as defined as: by having 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40mlU/ml and estradiol < 20 pg/mL or have had documented surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks prior.
- Able to provide written informed consent for the study.
- Able to swallow and retain orally administered medication.
Who cannot join
- Locally Advanced or metastatic breast cancer
- Prior therapy with chemotherapy or planned neoadjuvant chemotherapy
- Prior hormonal therapy including tamoxifen, aromatase inhibitors
- Pre-dominant histology other than invasive ductal or lobular carcinoma
- Concomitant other invasive malignancy.
- Hgb < 100 g/L, Platelets < 100 x 10^9 per liter, Absolute Neutrophil Count < 1.5 x 10^9/L
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- Bilirubin ≥ 1.5 times Upper Limit Normal (ULN)
- ALT ≥ 2.5 times ULN
- Albumin < 25 g/L
- INR/PTT > 1.5 times ULN
- Creatinine clearance calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of less than 50 mL/min/1.73m2.
- Cardiac abnormalities as evidenced by any of the following:
- Baseline QTcF interval ≥ 480 msec
- Clinically significant conduction abnormalities or arrhythmias
- Presence of cardiac pacemaker or defibrillator with a paced ventricular rhythm limiting ECG analysis.
- History or evidence of current ≥ Class II congestive heart failure as defined by New York Heart Association (NYHA).
- History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months.
- Clinically significant cardiomegaly, ventricular hypertrophy, or cardiomyopathy.
- Any serious known immediate or delayed hypersensitivity reaction(s) to GSK3326595, or idiosyncrasy to drugs chemically related to the investigational drugs.
- Current use of a prohibited medication or planned use of any forbidden medications during treatment with GSK3326595, which include chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal therapy (other than corticosteroids) while on treatment in this study. GSK3326595 should not be co-administered with potent inhibitors of either BCRP or Pgp such inhibitors include cyclosporine, tacrolimus, and ketoconazole
- Any clinically significant gastrointestinal (GI) abnormalities that may alter absorption, such as malabsorption syndrome, chronic gastrointestinal disease, or major resection of the stomach and/or bowels that could preclude adequate absorption of the study medication.
- Severe, uncontrolled systemic disease (respiratory, cardiac, renal, hepatic, bleeding)
- Currently active liver or biliary disease
- History of active HIV, Hepatitis B or C infection.
- Any other criteria which, in the investigator's opinion, renders the patient ineligible to be on study.
- Subjects with signs/symptoms suggestive of COVID-19 or known COVID-19 positive contacts in the past 14 days would be tested as per local Public Health and/or Institutional Guidelines. If patients are COVID-19 positive at the time of screening, they would be excluded from the trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Randomized Window of Opportunity Trial Evaluating Clinical and Biological Effects of PRMT5 Inhibitor, GSK3326595, in Early Stage Breast Cancer
This is a Phase II Randomized Window of Opportunity Trial Evaluating Clinical and Biological effects of PRMT5 inhibitor, GSK3326595, in Early Stage Breast Cancer
Read the detailed description
This is a phase II, randomized, open label, multi-center, parallel design, window of opportunity trial in up to 60 patients with early stage Hormone Receptor (HR) positive breast cancer evaluating GSK3326595. In a 2:1 randomization, patients will receive GSK3326595:no treatment for 15 +/- 3 days prior to breast surgery. There is no placebo in this trial.
- Conditions
- Breast Cancer
- Being tested
- GSK3326595
- Keywords
- Window of Opportunity, PRMT5 inhibitor, GSK3326595, Early Stage Breast Cancer, Hormone Receptor (HR) positive breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK3326595Drug
Also called PRMT5 inhibitor
GSK3326595 is a first-in-class small molecule PRMT5 inhibitor in form of an oral capsule.
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Participants randomized to treatment with GSK3326595 will be requested to take 15 +/- 3 days of the medication at the dose of 200 mg orally daily (2 capsules of 100 mg) prior to their breast cancer surgery or repeat biopsy. GSK3326595 is a first-in-class small molecule PRMT5 inhibitor in form of an oral capsule. Receives: Drug: GSK3326595 |
| No Intervention Arm | No intervention | Participants will receive no treatment for 15 +/- 3 days prior to breast surgery. There is no placebo in this trial. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete cell cycle arrest (CCCA)
The primary outcome is the proportion of patients who achieve a Complete Cell Cycle Arrest (CCCA), defined as a reduction in the proportion of Ki67 positively staining cells to ≤ 2.7%.
Measured: 2 years
Secondary outcomes (4)
Rate of complete cell cycle arrest (CCCA) in patients with wild-type TP53
The secondary outcome is to assess whether PRMT5 inhibition preferentially results in CCCA in patients with wild-type TP53.
Measured: 2 years
Assess whether PRMT5 inhibition results in reduced expression of ER-α signaling compared to patients with no treatment based on gene expression analysis.
A secondary outcome is to assess whether PRMT5 inhibition results in reduced expression of ER-α signaling.
Measured: 2 years
Assess whether PRMT5 inhibition results in changes in breast-cancer stem cell signature particularly FOXP1 compared to patients with no treatment based on gene expression analysis
A secondary outcome is to assess whether PRMT5 inhibition results in changes in breast-cancer stem cell signature particularly FOXP1.
Measured: 2 years
Perform molecular analysis to identify immunomodulatory effects of GSK3326595 determined by abundance of different immune cells in tumor (CD4, CD8, NK cells, macrophages, etc) in the tumors treated with GSK3326595 alone versus the untreated tumours.
A secondary outcome is to identify the immunomodulatory effects of GSK3326595, by performing exploratory analyses.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2020
- Study start8 Jun 2021
- Primary completion15 Aug 2022
- Study completion15 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase II, randomized, open label, multi-center, parallel design, window of opportunity trial
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Ontario Institute for Cancer Research, GlaxoSmithKline, London Regional Cancer Program, Canada, Hamilton Health Sciences Corporation
- Responsible party
- Sponsor
- Investigators
- John F. Hilton, MD, Principal investigator, The Ottawa Hospital Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04676516
- Sponsor's protocol ID
- OTT-19-06
- Acronym
- OTT-19-06
- Status last verified
- Oct 2022
- First submitted
- 28 Jul 2020
- Last updated
- 25 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Researchers may contact Dr. John Hilton for specific requests.
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized Window of Opportunity Trial Evaluating Clinical and Biological Effects of PRMT5 Inhibitor, GSK3326595, in Early Stage Breast Cancer
- ClinicalTrials.gov ID
- NCT04676516
- Acronym / sponsor ID
- OTT-19-06 / OTT-19-06
- Conditions
- Breast Cancer
- Keywords
- Window of Opportunity, PRMT5 inhibitor, GSK3326595, Early Stage Breast Cancer, Hormone Receptor (HR) positive breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Ontario Institute for Cancer Research, GlaxoSmithKline, London Regional Cancer Program, Canada, Hamilton Health Sciences Corporation
- Study start
- 8 Jun 2021 (actual)
- Primary completion
- 15 Aug 2022 (actual)
- Study completion
- 15 Aug 2022 (actual)
- First posted
- 21 Dec 2020 (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.
This is a Phase II Randomized Window of Opportunity Trial Evaluating Clinical and Biological effects of PRMT5 inhibitor, GSK3326595, in Early Stage Breast Cancer
Detailed description
This is a phase II, randomized, open label, multi-center, parallel design, window of opportunity trial in up to 60 patients with early stage Hormone Receptor (HR) positive breast cancer evaluating GSK3326595. In a 2:1 randomization, patients will receive GSK3326595:no treatment for 15 +/- 3 days prior to breast surgery. There is no placebo in this trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase II, randomized, open label, multi-center, parallel design, window of opportunity trial
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Drug: GSK3326595Participants randomized to treatment with GSK3326595 will be requested to take 15 +/- 3 days of the medication at the dose of 200 mg orally daily (2 capsules of 100 mg) prior to their breast cancer surgery or repeat biopsy. GSK3326595 is a first-in-class small molecule PRMT5 inhibitor in form of an oral capsule. |
| No Intervention Arm | No intervention | –Participants will receive no treatment for 15 +/- 3 days prior to breast surgery. There is no placebo in this trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Female patients with newly diagnosed histologically confirmed primary invasive breast cancer currently not undergoing any treatment while awaiting surgery
- Operable breast cancer as assessed by treating surgical oncologist
- Tumor ≥ 1.0 cm by palpation or imaging
- ER or PR positive (≥1%) breast adenocarcinoma
- Her2 negative as per ASCO 2018 guidelines 61
Key exclusion criteria (26 listed)
- Locally Advanced or metastatic breast cancer
- Prior therapy with chemotherapy or planned neoadjuvant chemotherapy
- Prior hormonal therapy including tamoxifen, aromatase inhibitors
- Pre-dominant histology other than invasive ductal or lobular carcinoma
- Concomitant other invasive malignancy.
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 |
|---|---|---|
| GSK3326595Also: PRMT5 inhibitorGSK3326595 is a first-in-class small molecule PRMT5 inhibitor in form of an oral capsule. | Drug | Experimental Arm |
Primary outcome
Complete cell cycle arrest (CCCA)
Time frame: 2 years
The primary outcome is the proportion of patients who achieve a Complete Cell Cycle Arrest (CCCA), defined as a reduction in the proportion of Ki67 positively staining cells to ≤ 2.7%.
4 secondary outcomes
Rate of complete cell cycle arrest (CCCA) in patients with wild-type TP53
Time frame: 2 years
Assess whether PRMT5 inhibition results in reduced expression of ER-α signaling compared to patients with no treatment based on gene expression analysis.
Time frame: 2 years
Assess whether PRMT5 inhibition results in changes in breast-cancer stem cell signature particularly FOXP1 compared to patients with no treatment based on gene expression analysis
Time frame: 2 years
Perform molecular analysis to identify immunomodulatory effects of GSK3326595 determined by abundance of different immune cells in tumor (CD4, CD8, NK cells, macrophages, etc) in the tumors treated with GSK3326595 alone versus the untreated tumours.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2022.
- Individual participant dataSharing planned: No. Researchers may contact Dr. John Hilton for specific requests.
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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.
John F. Hilton, MD principal investigator
The Ottawa Hospital Cancer Centre
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 GSK3326595 in people with Breast Cancer, run by Ottawa Hospital Research Institute at 1 site 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 10 inclusion and 26 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: finished, as of the sponsor's last update on 25 Oct 2022. 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 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Complete cell cycle arrest (CCCA) (time frame: 2 years). 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 25 Oct 2022.