Breast CancerPhase 2NCT04946227
Pembrolizumab and Paclitaxel in Hormone Receptor-positive, hyperMUTATted Metastatic Breast Cancer Identified by Whole exOme sequeNcing ('MUTATION2')
A Phase 2 study testing Pembrolizumab 200mg +Paclitaxel 80mg/m2 in people with Breast Cancer, run by Yonsei University at 1 site in South Korea.
Trial summary
Abbreviated Title :Pembrolizumab with paclitaxel in hypermutated breast cancer Trial Phase: Phase II Clinical Indication: Hormone receptor-positive metastatic breast cancer Trial Type: Interventional Type of control: None Route of administration: Intravenous Trial Blinding: None Treatment Groups : Pembrolizumab plus… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Pembrolizumab 200mg +Paclitaxel 80mg/m2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jul 2021to Dec 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male participants or female participants who are pre or postmenopausal women and at least 19 years of age on the day of signing informed consent with histologically or cytologically confirmed diagnosis of stage IV hormone receptor-positive breast cancer will be enrolled in this study.
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
- a WOCBP must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days, corresponding to time needed to eliminate any study treatments [e.g., 5 terminal half-lives for pembrolizumab and paclitaxel (52.7 hours)] after the last dose of study treatment.
- No prior systemic cytotoxic chemotherapy in the metastatic setting. Lines of endocrine or HER2-targeted therapy are not limited.
- No prior paclitaxel, except ≥12 months after last dose of chemotherapy for early breast cancer (if chemotherapy given)
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- Criteria of hypermutation should be met.
- Criteria of hypermutation: 70 nonsynonymous mutations per tumor per exome as the presumptive starting cut-off for upper 20% of mutation burden. we will revise cut-off after enrolling every 30 patients. That is, the criteria of hypermutation will be altered every 30 cases.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Subject who has biopsy-accessible tumor for WES. Biopsy on breast tumor or axillary nodes is acceptable if locoregional recurrence after primary surgery occurs or de novo stage IV breast cancer is diagnosed
- Documented disease progression on the most recent therapy. This is not applicable during prescreening phase. That is, tissue biopsy is possible while maintaining existing treatment.
- Life expectancy of > 12 weeks
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization.
- Have adequate organ function as defined in the following table(Table 2). Specimens must be collected within 10 days prior to the start of study treatment.
Who cannot join
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to allocation.
- Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
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- Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
- Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases (eg., whole brain radiation therapy, gamma-knife surgery or brain tumor removal) may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Has hypersensitivity (≥Grade 2 peripheral neuropathy) or contraindication to paclitaxel or any of its excipients.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV) infection: HIV-1 or HIV-2 antibody+ or HTLV-1 antibody+
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
- Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible.
- Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
- Has had an allogenic tissue/solid organ transplant.
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Division of Medical Oncology, Yonsei Cancer Center, Yonsei Univ. College of Medicine
Seoul
Joohyuk sohn, +82-2-2228-8135, oncosohn@yuhs.ac
About this study
Official title: Phase II Trial of Pembrolizumab and Paclitaxel in Hormone Receptor-positive, hyperMUTATted Metastatic Breast Cancer Identified by Whole exOme sequeNcing ('MUTATION2')
Abbreviated Title :Pembrolizumab with paclitaxel in hypermutated breast cancer Trial Phase: Phase II Clinical Indication: Hormone receptor-positive metastatic breast cancer Trial Type: Interventional Type of control: None Route of administration: Intravenous Trial Blinding: None Treatment Groups : Pembrolizumab plus paclitaxel Number of trial participants: Approximately 200 patients will be prescreened with whole exome sequencing. Then 52 patients will be enrolled in the treatment phase.
Estimated enrollment period :12 months Estimated duration of trial :The sponsor estimates that the trial will require approximately 24 months from the time the first subject signs the informed consent until the last subject's last visit.
Duration of Participation :24 months Estimated average length of treatment per patient :8 months
- Conditions
- Breast Cancer
- Being tested
- Pembrolizumab 200mg +Paclitaxel 80mg/m2
- Keywords
- pembrolizumab, hypermutated, hormone receptor-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.
Pembrolizumab 200mg +Paclitaxel 80mg/m2Drug
Pembrolizumab 200mg +Paclitaxel 80mg/m2
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor. Receives: Drug: Pembrolizumab 200mg +Paclitaxel 80mg/m2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR) by RECIST 1.1
rate of patients with complete remission (CR) or partial remission (PR) based on RESIST1.1
Measured: up to 24 months(RECIST will be done every 8 weeks)
Secondary outcomes (5)
Clinical benefit rate (CBR) by RECIST 1.1
CBR is defined as complete or partial response or stable disease for at least 24 weeks by RECIST 1.1
Measured: up to 24 months(RECIST will be done every 8 weeks)
Duration of response (DoR)
DoR is duration of response to progression/death/last follow-up
Measured: up to 24 months(RECIST will be done every 8 weeks)
Disease control rate (DCR) by RECIST 1.1
DCR is rate of patients with CR, PR, or SD per RECIST 1.1
Measured: up to 24 months(RECIST will be done every 8 weeks)
Progression-free survival (PFS) by RECIST 1.1
PFS is defined as time interval from cycle 1 day 1 to tumor progression/death/last follow-up
Measured: up to 24 months(RECIST will be done every 8 weeks)
Incidence of AE by CTCAE 5.0
Incidence of AE is based on CTCAE 5.0
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2021
- Study startJul 2021 (estimated)
- Primary completionDec 2022 (estimated)
- Study completionDec 2022 (estimated)
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 Yonsei UniversityThe 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
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joohyuk Joohyuk, Principal investigator, Severance Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04946227
- Sponsor's protocol ID
- 4-2020-1453
- Status last verified
- Jun 2021
- First submitted
- 3 Mar 2021
- Last updated
- 30 Jun 2021
- 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 30 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Pembrolizumab and Paclitaxel in Hormone Receptor-positive, hyperMUTATted Metastatic Breast Cancer Identified by Whole exOme sequeNcing ('MUTATION2')
- ClinicalTrials.gov ID
- NCT04946227
- Acronym / sponsor ID
- 4-2020-1453
- Conditions
- Breast Cancer
- Keywords
- pembrolizumab, hypermutated, hormone receptor-positive, breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- Jul 2021 (estimated)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 30 Jun 2021 (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.
Abbreviated Title :Pembrolizumab with paclitaxel in hypermutated breast cancer Trial Phase: Phase II Clinical Indication: Hormone receptor-positive metastatic breast cancer Trial Type: Interventional Type of control: None Route of administration: Intravenous Trial Blinding: None Treatment Groups : Pembrolizumab plus paclitaxel Number of trial participants: Approximately 200 patients will be prescreened with whole exome sequencing. Then 52 patients will be enrolled in the treatment phase.
Estimated enrollment period :12 months Estimated duration of trial :The sponsor estimates that the trial will require approximately 24 months from the time the first subject signs the informed consent until the last subject's last visit.
Duration of Participation :24 months Estimated average length of treatment per patient :8 months
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: Pembrolizumab 200mg +Paclitaxel 80mg/m2Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Male participants or female participants who are pre or postmenopausal women and at least 19 years of age on the day of signing informed consent with histologically or cytologically confirmed diagnosis of stage IV hormone receptor-positive breast cancer will be enrolled in this study.
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- No prior systemic cytotoxic chemotherapy in the metastatic setting. Lines of endocrine or HER2-targeted therapy are not limited.
- Criteria of hypermutation should be met.
- Criteria of hypermutation: 70 nonsynonymous mutations per tumor per exome as the presumptive starting cut-off for upper 20% of mutation burden. we will revise cut-off after enrolling every 30 patients. That is, the criteria of hypermutation will be altered every 30 cases.
Key exclusion criteria (25 listed)
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to allocation.
- Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
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 |
|---|---|---|
| Pembrolizumab 200mg +Paclitaxel 80mg/m2Pembrolizumab 200mg +Paclitaxel 80mg/m2 | Drug | Single Arm |
Primary outcome
Objective response rate (ORR) by RECIST 1.1
Time frame: up to 24 months(RECIST will be done every 8 weeks)
rate of patients with complete remission (CR) or partial remission (PR) based on RESIST1.1
5 secondary outcomes
Clinical benefit rate (CBR) by RECIST 1.1
Time frame: up to 24 months(RECIST will be done every 8 weeks)
Duration of response (DoR)
Time frame: up to 24 months(RECIST will be done every 8 weeks)
Disease control rate (DCR) by RECIST 1.1
Time frame: up to 24 months(RECIST will be done every 8 weeks)
Progression-free survival (PFS) by RECIST 1.1
Time frame: up to 24 months(RECIST will be done every 8 weeks)
Incidence of AE by CTCAE 5.0
Time frame: up to 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2021.
- Individual participant dataSharing planned: No
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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.
Joohyuk Joohyuk principal investigator
Severance Hospital
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 Pembrolizumab 200mg +Paclitaxel 80mg/m2 in people with Breast Cancer, run by Yonsei University at 1 site in South Korea.
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 15 inclusion and 25 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 30 Jun 2021. 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 South Korea. 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?
Contact Joohyuk sohn (+82-2-2228-8135, oncosohn@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) by RECIST 1.1 (time frame: up to 24 months(RECIST will be done every 8 weeks)). 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 30 Jun 2021.