Breast CancerPhase 2PERSEVERENCT04849364
Circulating Tumor DNA Enriched, Genomically Directed Post-neoadjuvant Trial for Patients With Residual Triple Negative Breast Cancer
A Phase 2 study testing Capecitabine, Talazoparib and Pembrolizumab in people with Breast Cancer and Triple Negative Breast Cancer, run by Bryan Schneider, MD at 13 sites in United States.
Trial summary
This is a 3-arm study stratified by plasma ctDNA. Patients with residual TNBC disease after pre-operative therapy will be assigned to 1 of 3 Arms based on plasma ctDNA positivity and genomic marker(s). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Triple Negative Breast Cancer
- What is being tested?
- Capecitabine, Talazoparib and Pembrolizumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 13 sitesUnited States
- Study dates
- 24 Aug 2021to 2 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- -Adequate laboratory values must be obtained within 21 days prior to starting arm therapy.
- Fasting total glucose ≤ 126 mg/dL
- HbA1C ≤ 5.7%
- Cholesterol < 300 mg/dL; 10.34 mmol/L
- Triglycerides < 300 mg/dL; 3.42 mmol/L
- General Exclusion Criteria
Show all 16Show fewer
- Clinically significant infections as judged by the treating physician.
- Stage IV (metastatic) disease, however no specific staging studies are required in the absence of symptoms or physical exam findings that would suggest distant disease.
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial. NOTE: Patients without a known history of being HIV positive do not require testing at screening. Patients who are known to be HIV positive will require testing as described to be eligible for this trial. Testing should be considered standard of care.
- Patients with evidence of chronic hepatitis B virus (HBV) infection, with undetectable HBV viral load within 6 months of registration are eligible for this trial. They should be on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable within 6 months of registration to be eligible for this trial. NOTE: Patients without a known history of being hepatitis positive do not require testing at screening. Patients who are known to be hepatitis positive will require testing as described to be eligible for this trial. Testing should be considered standard of care.
- Participants with unstable angina or a myocardial infarction within 12 months of study registration.
- Active second malignancy (except non-melanomatous skin cancer or incidental prostate cancer found on cystectomy): Active second malignancy is defined as a current need for cancer therapy or a high possibility (> 30%) of recurrence during the study. Previous contralateral breast cancer is allowable unless it meets "active" criteria as stated above.
- Inability to swallow pills.
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, safety of participation, or interpretation of results. This includes significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome) or any other serious medical condition or abnormality in clinical laboratory tests that meet these criteria in the investigator's opinion.
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to any of the study medications being used in this study.
- Treatment with any investigational agent within 30 days prior to study registration.
Who cannot join
- Any concurrent ocular or intraocular condition (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition.
- Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes.
- Active inflammatory (e.g., uveitis or vitritis) or infectious (e.g., conjunctivitis, keratitis, scleritis, or endophthalmitis) conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye.
- Symptomatic active lung disease, including pneumonitis
- History of or active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis). Patients currently receiving immunosuppressants for inflammatory bowel disease (e.g., sulfasalazine) are considered to have active disease and are therefore ineligible.
- Any active bowel inflammation (including diverticulitis)
- Symptomatic hypercalcemia requiring continued use of bisphosphonate or denosumab therapy. Bisphosphonate and denosumab therapy for bone metastases or osteopenia/osteoporosis is allowed.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Summit Health
Berkeley Heights, New Jersey, 07922
University of Alabama at Birmingham
Birmingham, Alabama, 35294
University of Chicago Medical Center
Chicago, Illinois, 60637
Memorial Healthcare System
Hollywood, Florida, 33028
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, 46202
University of Wisconsin
Madison, Wisconsin, 53705
Miami Cancer Institute at Baptist Health, Inc.
Miami, Florida, 33176
Froedtert and The Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Mays Cancer Center at UT Health San Antonio
San Antonio, Texas, 78229
Georgetown University
Washington D.C., District of Columbia, 20057
Advocate Aurora Research Institute (Illinois)
Wauwatosa, Wisconsin, 53226
Aurora Health Care
Wauwatosa, Wisconsin, 53226
Novant Health Cancer Institute
Winston-Salem, North Carolina, 27103
About this study
Official title: A Phase II Circulating Tumor DNA Enriched, Genomically Directed Post-neoadjuvant Trial for Patients With Residual Triple Negative Breast Cancer (PERSEVERE)
This is a 3-arm study stratified by plasma ctDNA. Patients with residual TNBC disease after pre-operative therapy will be assigned to 1 of 3 Arms based on plasma ctDNA positivity and genomic marker(s).
Read the detailed description
Participants that are plasma ctDNA positive with a genomic target will be assigned to one of the three groups in Arm 1 and receive genomically directed therapy.
- Arm 1a: DNA Repair pathway = talazoparib + capecitabine (CLOSED)
- Arm 1b: Immunotherapy pathway = pembrolizumab + capecitabine (CLOSED)
- Arm 1c: PI3K Pathway = inavolisib + capecitabine ---> +/- standard of care pembrolizumab
- Arm 1d: DNA Repair + Immunotherapy = talazoparib + capecitabine +/- standard of care pembrolizumab
Participants that are plasma ctDNA positive without a genomic target will be assigned to Arm 2 and receive capecitabine and pembrolizumab or treatment of physician's choice.
Participants that are plasma ctDNA negative will be assigned to Arm 3 and receive any of the following based on patient and physician decision: no therapy/observation, capecitabine and pembrolizumab or treatment of physician's choice.
- Conditions
- Breast Cancer, Triple Negative Breast Cancer
- Being tested
- Capecitabine, Talazoparib, Pembrolizumab, Inavolisib
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Also called Xeloda
Capecitabine 1000 mg/m2 BID Orally 14 days on and 7 days off Cycle = 21 days; Total of 8 cycles
TalazoparibDrug
Also called Talzenna
Talazoparib Cycle 1: 0.75 mg then Cycle 2-8: 1 mg Cycle = 21 days; Total of 8 cycles
PembrolizumabDrug
Also called Keytruda
Per standard of care.
InavolisibDrug
Also called GDC-0077
Inavolisib Cycle 1: 6 mg then Cycle 2-8: 9mg Orally 21 days on Cycle = 21 days; Total of 8 cycles
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Arm 1a: Patients who are ctDNA-positive and harbor a genomic target. DNA repair pathway = talazoparib + capecitabine (CLOSED)
Arm 1b: Patients who are ctDNA-positive and harbor a genomic target. Immunotherapy pathway = pembrolizumab + capecitabine (CLOSED)
Arm 1c: Patients who are ctDNA-positive and harbor a genomic target. PI3K Pathway = inavolisib + capecitabine ---> +/- standard of care pembrolizumab
Arm 1d: Patients who are ctDNA-positive and harbor a genomic target. DNA Repair + Immunotherapy = talazoparib + capecitabine +/- standard of care pembrolizumab Receives: Drug: Capecitabine; Drug: Talazoparib; Drug: Pembrolizumab; Drug: Inavolisib |
| Arm 2 | Active comparator | Arm 2 subjects have plasma ctDNA positive but do not have a genomically driven treatment option. Treatment of physician's choice will be given with consideration for capecitabine and pembrolizumab. Dose, schedule and duration of treatment to be determined by treating physician. Receives: Drug: Capecitabine; Drug: Pembrolizumab |
| Arm 3 | Active comparator | Arm 3 subjects have plasma ctDNA negative. Treatment of patient and physician's choice will be given with consideration for capecitabine and pembrolizumab. Dose, schedule and duration of treatment to be determined by treating physician. Receives: Drug: Capecitabine; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
ARM 1c: Disease Free Survival (DFS) at 2 Years
DFS is defined as the duration of time from arm assignment to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause.
Measured: 2 years
Secondary outcomes (7)
ARM 2: Disease Free Survival (DFS) at 2 Years
DFS is defined as the duration of time from arm assignment to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause.
Measured: 2 years
ARM 3:Disease Free Survival (DFS) at 2 Years
DFS is defined as the duration of time from arm assignment to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause.
Measured: 2 years
Overall Disease Free Survival (DFS)
Comparison of overall DFS in Arms 1c, 2, 3. DFS is defined as the duration of time from arm assignment to time of a DFS event such as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause
Measured: Up to 29 months
Overall Distant Disease Free Survival (DDFS)
DDFS is defined as the duration of time from arm assignment to time of recurrence of breast cancer outside the breast and/or death from any cause.
Measured: Up to 29 months
1-year Disease Free Survival (DFS)
Compare 1-year DFS in Arms 1c, 2, 3. DFS is defined as the duration of time from arm assignment to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause
Measured: 1 year
Overall Survival (OS) at 5 Year
Overall survival is defined as the time from date of treatment start until death from any cause.
Measured: 5 years
Number of Participants With Adverse Events
Adverse events (regardless of relationship with study drug) will be assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) criteria v5
Measured: Up to 16 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2021
- Study start24 Aug 2021
- Primary completion24 Oct 2024
- Study completion2 Dec 2024
Why it stopped: Funder Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bryan Schneider, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Pfizer, Foundation Medicine, Indiana University, Vera Bradley Foundation for Breast Cancer
- Responsible party
- Sponsor-investigator, Bryan Schneider, MD, Hoosier Cancer Research Network
- Investigators
- Bryan P Schneider, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04849364
- Sponsor's protocol ID
- HCRN BRE18-334
- Acronym
- PERSEVERE
- Status last verified
- May 2025
- First submitted
- 13 Apr 2021
- Last updated
- 31 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Circulating Tumor DNA Enriched, Genomically Directed Post-neoadjuvant Trial for Patients With Residual Triple Negative Breast Cancer (PERSEVERE)
- ClinicalTrials.gov ID
- NCT04849364
- Acronym / sponsor ID
- PERSEVERE / HCRN BRE18-334
- Conditions
- Breast Cancer, Triple Negative Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funder Decision
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Bryan Schneider, MDUniversity, hospital or other
- Collaborators
- Genentech, Inc., Pfizer, Foundation Medicine, Indiana University, Vera Bradley Foundation for Breast Cancer
- Study start
- 24 Aug 2021 (actual)
- Primary completion
- 24 Oct 2024 (actual)
- Study completion
- 2 Dec 2024 (actual)
- First posted
- 19 Apr 2021 (actual)
- Results
- Posted 31 May 2025
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 3-arm study stratified by plasma ctDNA. Patients with residual TNBC disease after pre-operative therapy will be assigned to 1 of 3 Arms based on plasma ctDNA positivity and genomic marker(s).
Detailed description
Participants that are plasma ctDNA positive with a genomic target will be assigned to one of the three groups in Arm 1 and receive genomically directed therapy.
- Arm 1a: DNA Repair pathway = talazoparib + capecitabine (CLOSED)
- Arm 1b: Immunotherapy pathway = pembrolizumab + capecitabine (CLOSED)
- Arm 1c: PI3K Pathway = inavolisib + capecitabine ---> +/- standard of care pembrolizumab
- Arm 1d: DNA Repair + Immunotherapy = talazoparib + capecitabine +/- standard of care pembrolizumab
Participants that are plasma ctDNA positive without a genomic target will be assigned to Arm 2 and receive capecitabine and pembrolizumab or treatment of physician's choice.
Participants that are plasma ctDNA negative will be assigned to Arm 3 and receive any of the following based on patient and physician decision: no therapy/observation, capecitabine and pembrolizumab or treatment of physician's choice.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Capecitabine, Drug: Talazoparib, Drug: Pembrolizumab, Drug: InavolisibArm 1a: Patients who are ctDNA-positive and harbor a genomic target. DNA repair pathway = talazoparib + capecitabine (CLOSED) Arm 1b: Patients who are ctDNA-positive and harbor a genomic target. Immunotherapy pathway = pembrolizumab + capecitabine (CLOSED) Arm 1c: Patients who are ctDNA-positive and harbor a genomic target. PI3K Pathway = inavolisib + capecitabine ---> +/- standard of care pembrolizumab Arm 1d: Patients who are ctDNA-positive and harbor a genomic target. DNA Repair + Immunotherapy = talazoparib + capecitabine +/- standard of care pembrolizumab |
| Arm 2 | Active comparator | Drug: Capecitabine, Drug: PembrolizumabArm 2 subjects have plasma ctDNA positive but do not have a genomically driven treatment option. Treatment of physician's choice will be given with consideration for capecitabine and pembrolizumab. Dose, schedule and duration of treatment to be determined by treating physician. |
| Arm 3 | Active comparator | Drug: Capecitabine, Drug: PembrolizumabArm 3 subjects have plasma ctDNA negative. Treatment of patient and physician's choice will be given with consideration for capecitabine and pembrolizumab. Dose, schedule and duration of treatment to be determined by treating physician. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- -Adequate laboratory values must be obtained within 21 days prior to starting arm therapy.
- Fasting total glucose ≤ 126 mg/dL
- HbA1C ≤ 5.7%
- Cholesterol < 300 mg/dL; 10.34 mmol/L
- Triglycerides < 300 mg/dL; 3.42 mmol/L
Key exclusion criteria (7 listed)
- Any concurrent ocular or intraocular condition (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition.
- Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes.
- Active inflammatory (e.g., uveitis or vitritis) or infectious (e.g., conjunctivitis, keratitis, scleritis, or endophthalmitis) conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye.
- Symptomatic active lung disease, including pneumonitis
- History of or active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis). Patients currently receiving immunosuppressants for inflammatory bowel disease (e.g., sulfasalazine) are considered to have active disease and are therefore ineligible.
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 |
|---|---|---|
| CapecitabineAlso: XelodaCapecitabine 1000 mg/m2 BID Orally 14 days on and 7 days off Cycle = 21 days; Total of 8 cycles | Drug | Arm 1, Arm 2, Arm 3 |
| TalazoparibAlso: TalzennaTalazoparib Cycle 1: 0.75 mg then Cycle 2-8: 1 mg Cycle = 21 days; Total of 8 cycles | Drug | Arm 1 |
| PembrolizumabAlso: KeytrudaPer standard of care. | Drug | Arm 1, Arm 2, Arm 3 |
| InavolisibAlso: GDC-0077Inavolisib Cycle 1: 6 mg then Cycle 2-8: 9mg Orally 21 days on Cycle = 21 days; Total of 8 cycles | Drug | Arm 1 |
Primary outcome
ARM 1c: Disease Free Survival (DFS) at 2 Years
Time frame: 2 years
DFS is defined as the duration of time from arm assignment to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause.
7 secondary outcomes
ARM 2: Disease Free Survival (DFS) at 2 Years
Time frame: 2 years
ARM 3:Disease Free Survival (DFS) at 2 Years
Time frame: 2 years
Overall Disease Free Survival (DFS)
Time frame: Up to 29 months
Overall Distant Disease Free Survival (DDFS)
Time frame: Up to 29 months
1-year Disease Free Survival (DFS)
Time frame: 1 year
Overall Survival (OS) at 5 Year
Time frame: 5 years
Number of Participants With Adverse Events
Time frame: Up to 16 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Bryan P Schneider, MD principal investigator
Indiana University
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Capecitabine, Talazoparib and Pembrolizumab in people with Breast Cancer and Triple Negative Breast Cancer, run by Bryan Schneider, MD at 13 sites in United States.
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 16 inclusion and 7 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: stopped early, as of the sponsor's last update on 31 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. 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?
Yes. Results are posted in the registry (first posted 31 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
ARM 1c: Disease Free Survival (DFS) at 2 Years (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 31 May 2025.