Metastatic Breast CancerPhase 2NCT04990921
Study of Palliative Radiation Combined with Pembrolizumab in Unresectable Metastatic Stage IV Breast Cancer
A Phase 2 study testing Palliative Radiation and Pembrolizumab in people with Metastatic Breast Cancer, run by University of Louisville at 1 site in United States.
Trial summary
This is a phase 2, open-label, single-arm trial designed to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) in combination with pembrolizumab following disease progression after two prior lines of standard therapy in unresectable metastatic stage IV breast cancer Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Palliative Radiation and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Sep 2021to 1 Jul 2031
- Phase
- Phase 2
- 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
- 1. Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures.
- 2. Female age ≥ 18 years at the time of informed consent. 3. Histologically confirmed diagnosis of breast cancer. 4. Disease stage: unresectable or metastatic stage IV breast cancer. 5. Candidate for palliative SBRT independent from study enrollment 6. Measurable disease, defined as at least 1 visceral or nodal/soft tissue breast cancer lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 10 mm as measured by Computer Tomography scan or Magnetic Resonance Imaging. Lymph nodes must measure ≥ 15 mm in their short axis to be considered measurable by Computer Tomography scan or Magnetic Resonance Imaging or Positron Emission Tomography-CT.
- 7. If subject received major surgery, must have recovered adequately from toxicity and/or complications from the intervention prior to enrollment.
- 8. Subject must have received two prior lines of therapy and include a taxane in the adjuvant/neoadjuvant or metastatic setting.
- Triple negative breast cancer patients must have received two lines of chemotherapy in the metastatic setting.
- ER+/ PR+, ER-/PR+, and ER+/PR- must have received prior Cyclin Dependent Kinase 4/6 Inhibitor in combination with Aromatase Inhibitor or fulvestrant. However, ER+/Her2 overexpressed patients are not required to have received CDK 4/6 inhibitor.
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- Her2 overexpressed breast cancer must have had prior trastuzumab/per (in the neoadjuvant/adjuvant or metastatic setting, and prior Ado-trastuzumab TDM1 therapy.
- 9. Adequate organ function determined within 14 days prior to enrollment, defined as follows:
- Absolute neutrophil (ANC) >1.5 x 109/L
- Platelet count>50 x 109/L
- Hemoglobin>8 g/dL
- Serum creatinine <2.0 x upper limit of normal
- Serum bilirubin < 2.0 x ULN OR direct bilirubin ≤ ULN for a subject with total bilirubin level > 2.0 x ULN
- Aspartate aminotransferase (AST) <2.5 x ULN OR <5 x ULN for subject with liver metastases
- Alanine aminotransferase (ALT) <2.5 x ULN OR <5 x ULN for subject with liver metastases
- International normalization ratio (INR) or prothrombin time (PT) <1.5 x ULN unless the subject is receiving anticoagulant therapy as long as PT and partial thromboplastin time (PTT)/activated PTT (aPTT) is within therapeutic range of intended use of anticoagulants
- Lactate dehydrogenase (LDH) levels ≤ 1.5 X upper limit of normal (ULN) within 28 days prior to enrollment
- Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to enrollment. If the urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- ECOG performance status of 0, 1 or 2.
Who cannot join
- <!-- -->
- > 4 Clinically active cerebral metastases. Subjects cerebral metastases may be enrolled, provided that there are less than 4 lesions as these may serve as a site of pallative SBRT
- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
- Any active autoimmune disease that in the judgement of the PI or sub-I could be significantly worsened by pembrolizumab
- Evidence of clinically significant immunosuppression such as the following:
- diagnosis of immunodeficiency;
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- concurrent opportunistic infection;
- receiving systemic immunosuppressive therapy (> 2 weeks) or within 7 days prior to the first dose of study treatment, including oral steroid doses > 20 mg/day of prednisone or equivalent Subjects that require intermittent use of bronchodilators or local steroid injection will not be excluded from the study.
- Subject has known sensitivity to any of the products or components to be administered during dosing
- Known human immunodeficiency virus (HIV) disease.
- Known acute or chronic hepatitis B or hepatitis C infection.
- Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease.
- Has a known history of active Bacillus tuberculosis.
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Those patients who would not otherwise have an indication for palliative SBRT
- Prior therapy with tumor vaccine (unless administered in the adjuvant setting).
- Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study.
- Expected to require other cancer therapy while on study with the exception of local radiation treatment to the site of bone and other metastasis for palliative pain management. Concurrent endocrine therapy or trastuzumab therapy is allowed if clinically indicated. Concurrent bone modifying agents (including denosumab or zoledronic acid) is allowed for patients with bone metastases.
- Female subject is pregnant or breast-feeding, or planning to become pregnant during study treatment or 4 months after the last dose of pembrolizumab
- Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment or 4 months after the last dose of pembrolizumab, whichever is later. Note: Women not of childbearing potential are defined as:
- postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age a high follicle stimulating hormone follicule stimulating hormone [FSH] level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.); OR
- have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR
- has a congenital or acquired condition that prevents childbearing.
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator's knowledge.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
James Graham Brown Cancer Center
Louisville, Kentucky, 40202
About this study
Official title: A Phase 2 Study of Palliative Radiation in Combination with Pembrolizumab in Subjects with Unresectable Metastatic Stage IV Breast Cancer: Twisted Pink
This is a phase 2, open-label, single-arm trial designed to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) in combination with pembrolizumab following disease progression after two prior lines of standard therapy in unresectable metastatic stage IV breast cancer
Read the detailed description
This study will enroll subjects who are female aged > 18 years at the time of informed consent with histologically confirmed diagnosis of breast cancer (unresectable or metastatic stage IV breast cancer). Subjects must have measurable disease and be a candidate for palliative stereotactic body radiation therapy (SBRT). Subjects must have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, 1, or 2 and adequate hematologic, hepatic, renal, and coagulation function. Subject must also have received two prior lines of FDA-approved therapy. Triple negative patients must have had prior exposure to taxane therapy either in the neoadjuvant/adjuvant or metastatic setting. ER + positive patients must have had prior cyclin dependent kinase (CDK) 4/6 inhibitor therapy. Her2 overexpressed patients must have had prior therapy with trastuzumab and ado-trastuzumab (TDM-1).
- Conditions
- Metastatic Breast Cancer
- Being tested
- Palliative Radiation and Pembrolizumab
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Palliative Radiation and PembrolizumabCombination product
Also called Keytruda
Stereotactic radiation therapy will be administered as clinically indicated.
| Study group | Role | What they receive |
|---|---|---|
| Palliative Radiation in Combination with Pembrolizumab | Experimental | Stereotactic radiation therapy will be delivered using either linac-based SBRT using 10x flattening filter-free (FFF) photons or Cyberknife Pencil Beam Technology utilizing 6X photons. Treatment will be delivered in 1-5 fractions. Fractionation and total dose (1500 - 3000 cGy) will depend on the site of disease, previous radiation treatment, and patient symptomatology.
Pembrolizumab is supplied as pembrolizumab 100 mg/4 mL vials (25 mg/mL) solution for intravenous infusion. Pembrolizumab at a dose of 200 mg will be administered intravenously every 3 weeks (± 3 days). Receives: Combination Product: Palliative Radiation and Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Outcome Measure
Overall Response Rate (complete response [CR]+partial response [PR] by investigator assessment using modified RECIST v1.1) at week 24
Measured: 3.0 years
Secondary outcomes (3)
Secondary Outcome Measures-Best Overall Response Rate
Best Overall Response Rate (complete response [CR]+partial response [PR] by investigator assessment using modified RECIST v1.1)
Measured: 3.0 years
Secondary Outcome Measures-Progression-free Survival
Progression-free Survival (PFS)
Measured: 3.0 years
Secondary Outcome Measures-Incidence of treatment-emergent and treatment-related adverse events
Incidence of treatment-emergent and treatment-related adverse events as defined by
Measured: 3.0 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2021
- Study start2 Sep 2021
- Primary completion1 Jul 2031 (estimated)
- Study completion1 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by University of LouisvilleThe 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
- Model description
- The primary objective is to evaluate the efficacy of SBRT in combination with pembrolizumab as assessed by Overall Response Rate in subjects with stage IV breast cancer.
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Louisville
- Sponsor type
- University, hospital or other
- Collaborators
- James Graham Brown Cancer Center
- Responsible party
- Principal investigator, Elizabeth Riley, University of Louisville
- Investigators
- Elizabeth Riley, MD, Principal investigator, UL Health Brown Cancer Center Deputy Director, Health Affairs
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04990921
- Sponsor's protocol ID
- Twisted Pink Foundation
- Status last verified
- May 2024
- First submitted
- 23 Jun 2021
- Last updated
- 20 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data identifying the subjects and subject research records that are maintained in the Clinical Trials Office (CTO) will be made available to the study sponsor or its authorized representatives during monitoring visits. Many source documents may contain identifiable information. During internal audits, members of the James Graham Brown Cancer Center (JGBCC) Data Safety Monitoring Committee will have access to subject's research records maintained in the CTO. If required, these records will be made available to the FDA, Office for Human Research Protections (OHRP), Office of Civil Rights, and other authorized local/state/federal agencies.
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Palliative Radiation in Combination with Pembrolizumab in Subjects with Unresectable Metastatic Stage IV Breast Cancer: Twisted Pink
- ClinicalTrials.gov ID
- NCT04990921
- Acronym / sponsor ID
- Twisted Pink Foundation
- Conditions
- Metastatic Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Collaborators
- James Graham Brown Cancer Center
- Study start
- 2 Sep 2021 (actual)
- Primary completion
- 1 Jul 2031 (estimated)
- Study completion
- 1 Jul 2031 (estimated)
- First posted
- 5 Aug 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.
This is a phase 2, open-label, single-arm trial designed to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) in combination with pembrolizumab following disease progression after two prior lines of standard therapy in unresectable metastatic stage IV breast cancer
Detailed description
This study will enroll subjects who are female aged > 18 years at the time of informed consent with histologically confirmed diagnosis of breast cancer (unresectable or metastatic stage IV breast cancer). Subjects must have measurable disease and be a candidate for palliative stereotactic body radiation therapy (SBRT). Subjects must have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, 1, or 2 and adequate hematologic, hepatic, renal, and coagulation function. Subject must also have received two prior lines of FDA-approved therapy. Triple negative patients must have had prior exposure to taxane therapy either in the neoadjuvant/adjuvant or metastatic setting. ER + positive patients must have had prior cyclin dependent kinase (CDK) 4/6 inhibitor therapy. Her2 overexpressed patients must have had prior therapy with trastuzumab and ado-trastuzumab (TDM-1).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The primary objective is to evaluate the efficacy of SBRT in combination with pembrolizumab as assessed by Overall Response Rate in subjects with stage IV breast cancer.
| Arm | Type | Receives |
|---|---|---|
| Palliative Radiation in Combination with Pembrolizumab | Experimental | Combination Product: Palliative Radiation and PembrolizumabStereotactic radiation therapy will be delivered using either linac-based SBRT using 10x flattening filter-free (FFF) photons or Cyberknife Pencil Beam Technology utilizing 6X photons. Treatment will be delivered in 1-5 fractions. Fractionation and total dose (1500 - 3000 cGy) will depend on the site of disease, previous radiation treatment, and patient symptomatology. Pembrolizumab is supplied as pembrolizumab 100 mg/4 mL vials (25 mg/mL) solution for intravenous infusion. Pembrolizumab at a dose of 200 mg will be administered intravenously every 3 weeks (± 3 days). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 1. Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures.
- 2. Female age ≥ 18 years at the time of informed consent. 3. Histologically confirmed diagnosis of breast cancer. 4. Disease stage: unresectable or metastatic stage IV breast cancer. 5. Candidate for palliative SBRT independent from study enrollment 6. Measurable disease, defined as at least 1 visceral or nodal/soft tissue breast cancer lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 10 mm as measured by Computer Tomography scan or Magnetic Resonance Imaging. Lymph nodes must measure ≥ 15 mm in their short axis to be considered measurable by Computer Tomography scan or Magnetic Resonance Imaging or Positron Emission Tomography-CT.
- 7. If subject received major surgery, must have recovered adequately from toxicity and/or complications from the intervention prior to enrollment.
- 8. Subject must have received two prior lines of therapy and include a taxane in the adjuvant/neoadjuvant or metastatic setting.
- 9. Adequate organ function determined within 14 days prior to enrollment, defined as follows:
Key exclusion criteria (24 listed)
- <!-- -->
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 |
|---|---|---|
| Palliative Radiation and PembrolizumabAlso: KeytrudaStereotactic radiation therapy will be administered as clinically indicated. | Combination product | Palliative Radiation in Combination with Pembrolizumab |
Primary outcome
Primary Outcome Measure
Time frame: 3.0 years
Overall Response Rate (complete response [CR]+partial response [PR] by investigator assessment using modified RECIST v1.1) at week 24
3 secondary outcomes
Secondary Outcome Measures-Best Overall Response Rate
Time frame: 3.0 years
Secondary Outcome Measures-Progression-free Survival
Time frame: 3.0 years
Secondary Outcome Measures-Incidence of treatment-emergent and treatment-related adverse events
Time frame: 3.0 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2025.
- Individual participant dataSharing planned: Yes. Data identifying the subjects and subject research records that are maintained in the Clinical Trials Office (CTO) will be made available to the study sponsor or its authorized representatives during monitoring visits. Many source documents may contain identifiable information. During internal audits, members of the James Graham Brown Cancer Center (JGBCC) Data Safety Monitoring Committee will have access to subject's research records maintained in the CTO. If required, these records will be made available to the FDA, Office for Human Research Protections (OHRP), Office of Civil Rights, and other authorized local/state/federal agencies.
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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.
Elizabeth Riley, MD principal investigator
UL Health Brown Cancer Center Deputy Director, Health Affairs
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 Palliative Radiation and Pembrolizumab in people with Metastatic Breast Cancer, run by University of Louisville at 1 site 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 19 inclusion and 24 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: looking for participants now, as of the sponsor's last update on 20 Feb 2025. 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 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?
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?
Contact Elizabeth Riley, MD (502 562-4370, beth.riley@louisville.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Outcome Measure (time frame: 3.0 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 20 Feb 2025.