Study of Palliative Radiation Combined with Pembrolizumab in Unresectable Metastatic Stage IV Breast Cancer

NCT04990921 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Twisted Pink Foundation
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measure

  Overall Response Rate (complete response \[CR\]+partial response \[PR\] by investigator assessment using modified RECIST v1.1) at week 24

  3.0 years

Secondary Outcomes (3)

• Secondary Outcome Measures-Best Overall Response Rate

  3.0 years

• Secondary Outcome Measures-Progression-free Survival

  3.0 years

• Secondary Outcome Measures-Incidence of treatment-emergent and treatment-related adverse events

  3.0 years

Study Arms (1)

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).

Combination Product: Palliative Radiation and Pembrolizumab

Interventions

Palliative Radiation and Pembrolizumab COMBINATION_PRODUCT

Stereotactic radiation therapy will be administered as clinically indicated.

Also known as: Keytruda

Palliative Radiation in Combination with Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures.
• \. 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.
• \. If subject received major surgery, must have recovered adequately from toxicity and/or complications from the intervention prior to enrollment.
• \. 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.
• Her2 overexpressed breast cancer must have had prior trastuzumab/per (in the neoadjuvant/adjuvant or metastatic setting, and prior Ado-trastuzumab TDM1 therapy.
• \. 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

You may not qualify if:

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• \> 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;
• 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

Sponsors & Collaborators

• University of Louisville: lead
• James Graham Brown Cancer Center: collaborator

Study Sites (1)

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Elizabeth Riley, MD

  UL Health Brown Cancer Center Deputy Director, Health Affairs

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elizabeth Riley, MD

CONTACT

502 562-4370; beth.riley@louisville.edu

Kathleen Coons

CONTACT

502 852-9127; kjcoon01@louisville.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: August 5, 2021
• Study Start: September 2, 2021
• Primary Completion (Estimated): July 1, 2031
• Study Completion (Estimated): July 1, 2031
• Last Updated: February 20, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will become available during the 3 year period of enrollment until long term analyses is complete and the study is terminated.

Locations

US (1)