Trial Title:
High Dose Radiation Therapy With Pembrolizumab and Chemotherapy for the Treatment of Patients With PD-L1 Positive Metastatic Triple Negative Breast Cancer
NCT ID:
NCT06492759
Condition:
Anatomic Stage IV Breast Cancer AJCC v8
Metastatic Triple-Negative Breast Carcinoma
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Gemcitabine
Pembrolizumab
Immunoglobulins
Immunoglobulin G
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Radiation Therapy
Description:
Undergo radiation therapy
Arm group label:
Treatment (radiation, pembrolizumab, chemotherapy)
Other name:
Cancer Radiotherapy, Energy Type, Irradiate, Irradiated, irradiation, Radiation, Radiation Therapy, Therapy, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Treatment (radiation, pembrolizumab, chemotherapy)
Other name:
1374853-91-4, BCD-201, Immunoglobulin G4, Anti-(Human Programmed Cell Death 1); Humanized Mouse Monoclonal (228-L-proline(H10-S>P))gamma 4 Heavy Chain (134-218')-disulfide with Humanized
Other name:
Monoclonal Kappa Light Chain Dimer (226-226'':229-229'')-bisdisulfide, Keytruda, Lambrolizumab, MK-3475, PEMBROLIZUMAB, Pembrolizumab, Biosimilar BCD-201, SCH 900475
Intervention type:
Drug
Intervention name:
Nab-paclitaxel
Description:
Given IV
Arm group label:
Treatment (radiation, pembrolizumab, chemotherapy)
Other name:
ABI 007, ABI-007, ABI-007, Abraxane, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound
Other name:
Paclitaxel, nanoparticle paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, Paclitaxel nanoparticle albumin-bound,
Other name:
Paclitaxel Protein-Bound, protein-bound paclitaxel, Protein-bound Paclitaxel
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Given IV
Arm group label:
Treatment (radiation, pembrolizumab, chemotherapy)
Other name:
33069-62-4,5Beta,20-epoxy-1,2alpha,4,7beta,10beta,13alpha-hexahydroxytax-11-en-9-one,4,10-Diacetate 2-Benzoate 13-Ester with (2R,3S)-N-Benzoyl-3-phenylisoserine, [2aR-[2a Alpha,4beta,4a beta,6beta
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Given IV
Arm group label:
Treatment (radiation, pembrolizumab, chemotherapy)
Other name:
SP-4-2)-diammine[1,1-cyclobutanedicarboxylato(2--)-O,O']platinum, 1,1-cyclobutanedicarboxylic acid platinum complex, 41575-94-4, Blastocarb, Carboplat, CARBOPLATIN,
Other name:
Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, CBDCA, cis-diammine(1,1-cyclobutanedicarboxylato) platinum(II),
Other name:
complex, 41575-94-4, Blastocarb, Carboplat, CARBOPLATIN, Carboplatin, Carboplatin Hexal, Carboplatino, Carboplatinum,
Other name:
Carbosin, Carbosol, Carbotec, CBDCA, cis-diammine(1,1-cyclobutanedicarboxylato) platinum(II), Cis-Diammine(cyclobutane-1,1-dicarboxylato)platinum,
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Given IV
Arm group label:
Treatment (radiation, pembrolizumab, chemotherapy)
Other name:
1-(2-Oxo-4-amino-1,2-dihydropyrimidin-1-yl)-2-deoxy-2,2-difluororibose, 2'Deoxy-2',2'-Difluorocytidine, 95058-81-4, dFdC, dFdCyd, Difluorodeoxycytidine, Gemcitabine, GEMCITABINE,
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (radiation, pembrolizumab, chemotherapy)
Other name:
Biopsy, BIOPSY_TYPE
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (radiation, pembrolizumab, chemotherapy)
Other name:
CAT, CAT Scan, Computed Axial Tomography, Computed Tomography, Computerized Axial Tomography,Computerized Axial Tomography,
Intervention type:
Procedure
Intervention name:
Bone Scan
Description:
Undergo bone scan
Arm group label:
Treatment (radiation, pembrolizumab, chemotherapy)
Other name:
Bone Scan, bone scan, Bone Scan, Bone Scan, Bone Scan, Bone Scintigraphy
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (radiation, pembrolizumab, chemotherapy)
Other name:
Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection
Intervention type:
Other
Intervention name:
Medical Chart Review
Description:
Ancillary studies
Arm group label:
Treatment (radiation, pembrolizumab, chemotherapy)
Other name:
Chart Review, Medical Chart Review
Summary:
This phase II trial tests how well radiation therapy with pembrolizumab and chemotherapy
(paclitaxel or nab-paclitaxel or carboplatin and gemcitabine) works in treating patients
with PD-L1 positive triple negative breast cancer that has spread from where it first
started (primary site) to other places in the body (metastatic). Radiation therapy uses
high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink
tumors. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the
body's immune system attack the tumor, and may interfere with the ability of tumor cells
to grow and spread. Paclitaxel is in a class of medications called antimicrotubule
agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel
is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side
effects and work better than other forms of paclitaxel. Carboplatin is in a class of
medications known as platinum-containing compounds. It works by killing, stopping or
slowing the growth of cancer cells. Gemcitabine is a chemotherapy drug that blocks the
cells from making DNA and may kill cancer cells. High dose radiation therapy with
pembrolizumab and chemotherapy may effective in treating patients with PD-L1 positive
metastatic triple negative breast cancer.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the 12 month progression-free survival (PFS) in PD-L1 positive, triple
negative breast cancer patients treated with high dose radiotherapy before and
concurrently with the first cycle of pembrolizumab plus chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate the objective response rate (ORR) in non-irradiated lesions nine weeks
after the first dose of pembrolizumab in PD-L1 positive, triple negative breast cancer
patients treated with high dose radiotherapy before and concurrently with the first cycle
pembrolizumab plus chemotherapy (ORR per Response Evaluation Criteria in Solid Tumors
[RECIST] 1.1).
II. To determine if targeted, high dose radiotherapy to up to 3 metastatic sites in
combination with pembrolizumab plus chemotherapy in patients with metastatic triple
negative breast cancer (> 2 sites) adversely increases the frequency and severity of
toxicities associated with radiotherapy or pembrolizumab plus chemotherapy when
administered separately.
III. To determine progression-free survival (PFS) in breast cancer patients treated with
high dose radiotherapy, pembrolizumab, and chemotherapy.
EXPLORATORY OBJECTIVES:
I. To collect, store, and analyze circulating tumor deoxyribonucleic acid (ctDNA) in
metastatic breast cancer patients treated with radiotherapy, pembrolizumab, and
chemotherapy to determine the relationship between ctDNA and PFS and ORR.
II. To collect, store and analyze tumor tissue from a non-irradiated metastatic breast
cancer site before and after radiotherapy to explore the immune tumor microenvironment
and the immunoscore, and the relationship between the immunoscore and ORR and PFS in
metastatic breast cancer patients treated with pembrolizumab and chemotherapy.
OUTLINE:
Patients undergo radiation therapy once every other day for 3 doses. Beginning within 48
hours of their first dose of radiation therapy, patients receive standard of care
pembrolizumab intravenously (IV) on day 1 of each cycle. Cycles repeat every 21 days in
the absence of disease progression or unacceptable toxicity. Patients also receive 1 of 3
standard of care chemotherapy options: nab-paclitaxel IV on days 1, 8, and 15 of each
cycle, or paclitaxel IV on days 1, 8, and 15 of each cycle, or carboplatin IV and
gemcitabine IV on days 1 and 8 of each cycle. Cycles of nab-paclitaxel and paclitaxel
repeat every 28 days and cycles of carboplatin and gemcitabine repeat every 21 days in
the absence of disease progression or unacceptable toxicity. Additionally, patients
undergo a biopsy at baseline and 2 weeks after radiation therapy and also undergo
computed tomography (CT) scans, bone scans and blood sample collections throughout the
trial.
After completion of study treatment, patients are followed up every 12 weeks.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Biopsy proven metastatic PD-L1 positive triple negative breast cancer with at least
2 sites of measurable metastatic disease on imaging
- Estrogen receptor (ER) and progesterone receptor (PR) negativity are defined as
≤ 10% of cells expressing hormonal receptors via immunohistochemistry (IHC)
analysis
- HER2 negativity is defined as either of the following by local laboratory
assessment
- In situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 < 2.0 or
single probe average HER2 gene copy number < 4 signals/cell) or
- IHC 0 or IHC 1+. If more than one test result is available and not all
results meet the inclusion criterion definition, all results should be
discussed with the Medical Monitor to establish eligibility of the patient
- PD-L1 positive as defined by Dako 22c3 assay PD-L1 combined positive score (CPS) ≥
10
- Appropriate stage for study entry based on the following diagnostic workup:
- History and physical examination within 60 days prior to registration
- Clinical grade CT scans of the chest, abdomen, and pelvis with radionuclide
bone scan or whole body positron emission tomography (PET)/CT documenting
metastatic disease within 4 weeks of the start of radiotherapy on this protocol
with or without magnetic resonance imaging (MRI), as needed, documenting site
of metastatic disease to be treated on protocol
- Patient must be eligible for radiotherapy as determined by their treating physician
- Patient must be eligible for immunotherapy and taxane chemotherapy as determined by
their treating physician
- At least 1 metastatic site amenable to high dose radiotherapy
- Be willing and able to provide written informed consent for the trial
- Ages ≥ 18 years of age
- Biopsy proven metastatic PD-L1 positive triple negative breast cancer with at least
2 sites of measurable metastatic disease on imaging
- Estrogen receptor (ER) and progesterone receptor (PR) negativity are defined as
≤ 10% of cells expressing hormonal receptors via immunohistochemistry (IHC)
analysis
- HER2 negativity is defined as either of the following by local laboratory
assessment
- In situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 < 2.0 or
single probe average HER2 gene copy number < 4 signals/cell) or
- IHC 0 or IHC 1+. If more than one test result is available and not all
results meet the inclusion criterion definition, all results should be
discussed with the Medical Monitor to establish eligibility of the patient
- PD-L1 positive as defined by Dako 22c3 assay PD-L1 combined positive score (CPS) ≥
10
- Appropriate stage for study entry based on the following diagnostic workup:
- History and physical examination within 60 days prior to registration
- Clinical grade CT scans of the chest, abdomen, and pelvis with radionuclide
bone scan or whole body positron emission tomography (PET)/CT documenting
metastatic disease within 4 weeks of the start of radiotherapy on this protocol
with or without magnetic resonance imaging (MRI), as needed, documenting site
of metastatic disease to be treated on protocol
- Patient must be eligible for radiotherapy as determined by their treating physician
- Patient must be eligible for immunotherapy and taxane chemotherapy as determined by
their treating physician
- At least 1 metastatic site amenable to high dose radiotherapy
- Be willing and able to provide written informed consent for the trial
- Ages ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2, Karnofsky
performance status (KPS) ≥ 60%
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST, version
1.1)
- Absolute neutrophil count ≥ 1500/mcL (obtained within 14 days prior to first study
treatment)
- Platelet count ≥ 100,000/mcL (obtained within 14 days prior to first study
treatment)
- Hemoglobin ≥ 9.0 g/dL (obtained within 14 days prior to first study treatment)
(Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] ≥
9.0g/dL is acceptable)
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x the upper
limit of normal (ULN) with the following exceptions (obtained within 14 days prior
to first study treatment):
* Patients with documented liver metastases: AST and ALT ≤ 5 x ULN
- Serum bilirubin ≤ 1.5 x ULN (obtained within 14 days prior to first study treatment)
* Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may
be enrolled
- Calculated creatinine clearance ≥ 30 mL/min (obtained within 14 days prior to first
study treatment)
- For females of child-bearing potential, negative serum or urine pregnancy test
within 14 days prior to radiation simulation
- The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
- Prior Treatment:
- Patients may or may not have received radiotherapy or neoadjuvant or adjuvant
chemotherapy in the treatment of their initial, non-metastatic breast cancer,
but must be entered on study after their last dose of radiotherapy, last cycle
of chemotherapy and biologic therapy (if applicable) and have sufficient
resolution of side effects per physician assessment at time of radiotherapy.
Prior immunotherapy for treatment of early stage breast cancer is allowed if
metastatic recurrence occurs ≥ 6 months after last dose of immunotherapy
- Patients must have not active wound healing issues from surgery and sufficient
resolution of surgical side effects, per physician assessment, at time of
radiotherapy
- Patients are not eligible if they have received chemotherapy in the
advanced/metastatic setting
- During radiotherapy, no other investigation or commercial agents or therapy for
cancer other than bisphosphonate or receptor activator nuclear kappaB ligand
(RANK-L) inhibitor, pembrolizumab, and nab-paclitaxel, paclitaxel, carboplatin
or gemcitabine should be administered
- Patients may have received bisphosphonates or rank ligand inhibitors prior to
enrollment on study
Exclusion Criteria:
- Prior chemotherapy or targeted therapy for metastatic triple negative breast cancer
before start of pembrolizumab plus partner chemotherapy. Prior chemotherapy
(including taxanes) administered in the context of curative therapy (if treatment
was completed > 6 months) prior to enrollment into the trial is allowed
- Previous radiation to the metastases to be treated with radiation on this protocol
- Untreated central nervous system (CNS) disease (patients with stable CNS disease for
at least 28 days and asymptomatic treated CNS metastases are permitted)
- Uncontrolled pleural effusion, pericardial effusion or ascites
* Patients with indwelling catheters (e.g., Pleurx) are allowed
- Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or
corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use
of bisphosphonate therapy or denosumab
* Patients who are receiving bisphosphonate therapy specifically to prevent skeletal
prevents and who do not have a history of clinically significant hypercalcemia are
eligible
- History (Hx) of autoimmune disease that has required systemic treatment (i.e. with
use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (e.g.., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered
a form of systemic treatment
- Use of chronic systemic glucocorticoid or immunosuppressive medications at time of
enrollment (prednisone or equivalent steroid dose of > 10mg for > 2 weeks)
- Prior allogeneic stem cell or solid organ transplantation
- Severe, active co-morbidity such as congestive heart failure (CHF) or unstable
angina within last 6 months, transmural myocardial infarction (MI) within the last 6
months
- Acute bacterial or fungal infection requiring IV antibiotics at time of registration
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
* History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Chronic obstructive pulmonary disease (COPD) or other respiratory illness requiring
hospitalization at time of registration
- HIV positive with CD4 count < 200 cells/ microliter
- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of
the skin that has undergone potentially curative therapy. Indolent cancers (such as
low risk prostate or in-situ cancers) that are not being treated, are acceptable
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the best
interest of the subject to participate, in the opinion of the treating investigator.
Examples include:
- Major surgical procedure within 28 days prior to randomization or anticipation
of the need for a major surgical procedure during the course of the study other
than for diagnosis
- Known hypersensitivity to nab-paclitaxel or to any of the excipients
- 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 trial, starting with the pre-screening or screening visit
through 90 days after the last dose of trial treatment
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Emory University Hospital/Winship Cancer Institute
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Contact:
Last name:
Ashley Lynn Trumbull
Phone:
404-778-3969
Email:
ashley.lynn.trumbull@emory.edu
Investigator:
Last name:
Manali A. Bhave, MD
Email:
Principal Investigator
Start date:
October 1, 2024
Completion date:
February 13, 2026
Lead sponsor:
Agency:
Emory University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Emory University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06492759
