Radiotherapy in Combo With Chemo and Immunotherapy in Patients With PD-L1 Positive Metastatic TNBC
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|ClinicalTrials.gov Identifier: NCT05233696|
Recruitment Status : Recruiting
First Posted : February 10, 2022
Last Update Posted : March 3, 2022
|Condition or disease||Intervention/treatment||Phase|
|Triple Negative Breast Cancer Locally Advanced Breast Cancer Unresectable Breast Carcinoma Metastatic Breast Cancer PD-L1 Gene Mutation||Drug: Nab-paclitaxel Drug: Paclitaxel Radiation: Radiation Therapy Drug: Pembrolizumab||Phase 2|
Patients with locally advanced unresectable or metastatic PD-L1 positive TNBC will be treated with radiation to one-four sites of metastasis amenable to radiation (sites of disease to be selected at the discretion of the treating radiation oncologist) followed by initiation of systemic therapy with pembrolizumab plus nab-paclitaxel/paclitaxel. Patients will be treated with pembrolizumab plus nab-paclitaxel/paclitaxel within 7 days of completion of radiation. Repeat imaging of all sites of disease will be performed every 9 weeks and response will be assessed according to RECIST 1.1.
This is a two-stage, single-arm phase II study. Utilizing time-to-event outcomes, the investigators assumed an uninteresting 1-year PFS rate of 39% and a positive 1-year PFS rate of 60%. The first stage will enroll 17 subjects, with an additional 12 subjects to be enrolled in stage 2 if the trial is not stopped due to futility, for a total of 29 subjects. Enrollment will not be paused after the first stage of enrollment. At the time of the interim analysis the investigators would expect approximately 12 patients to have completed 1-year follow-up.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Radiotherapy in Combination With Chemotherapy and Immunotherapy in Patients With PD-L1-Positive Metastatic Triple-Negative Breast Cancer|
|Actual Study Start Date :||January 4, 2022|
|Estimated Primary Completion Date :||April 19, 2025|
|Estimated Study Completion Date :||April 2026|
Experimental: RT followed by nab-paclitaxel/paclitaxel plus pembrolizumab
Nab-paclitaxel/paclitaxel plus pembrolizumab will be started within 7 days of completion of RT.
All patients are encouraged to receive nab-paclitaxel 100 mg/m2 IV D1 and D8 every 21 days (in combination with pembrolizumab) for at least 4-6 cycles per institutional standards and treating physicians' recommendations.
Other Name: Abraxane
Paclitaxel can be substituted for nab-paclitaxel at the discretion of the treating physician 80 mg/m2 IV D1 and D8 every 21 days.
Other Name: Abraxane
Radiation: Radiation Therapy
The treating radiation oncologist will select 1-4 sites of metastatic disease to target with radiation. All sites of disease may be targeted with radiation. Sites of metastatic disease planned to be biopsied should not be radiated.
Patients will receive pembrolizumab 200 mg D1 every 21 days.
Other Name: Keytruda
- 1 year progression free survival rate [ Time Frame: 36 months ]To determine the efficacy of radiotherapy in combination with chemotherapy plus immunotherapy as defined by 1-year PFS rate in patients with PD-L1-positive metastatic TNBC.
- Rate of in-field tumor control [ Time Frame: 36 months ]In-field tumor control will be defined as stable disease (SD), partial remission (PR), or complete remission (CR), of the target lesion, by RECIST 1.1 criteria.
- Determine overall response rate (ORR) [ Time Frame: 36 months ]Determined by RECIST 1.1
- Determine clinical benefit rate (CBR) [ Time Frame: 36 months ]Defined as SD, PR + CR, of the target lesion, by RECIST 1.1 criteria.
- Duration of response [ Time Frame: 36 months ]Duration of response by RECIST 1.1
- Progression free survival [ Time Frame: 36 months ]PFS will be measured from the date of initiation of nab-paclitaxel/paclitaxel plus pembrolizumab to the time of tumor progression or death from any cause
- Evaluate the tolerability of radiotherapy added to the combination of chemotherapy and immunotherapy [ Time Frame: 36 months ]Adverse events will be assessed according to NCI CTCAE v5.0.
- Evaluate change in immune cell populations by IHC. [ Time Frame: 36 months ]Serial tumor biopsies will be obtained in a subset of patients and changes in immune cell populations and activation profiles will be evaluated by IHC.
- Evaluate change in immune cell populations in blood samples using flow cytometry and gene expression profiling. [ Time Frame: 36 months ]Peripheral blood samples will be obtained pre-treatment and at various timepoints after treatment and evaluated by flow cytometry for B cell, NK cell, and CD8, CD4, and regulatory T cell populations including markers of activation and exhaustion (TIM-3, , LAG-3, and PD-L1) and gene expression. Fold change compared to baseline will be determined.
- Evaluate changes in markers of immune cell activation using IHC. [ Time Frame: 36 months ]Serial tumor biopsies will be obtained in a subset of patients and changes in immune cell populations and activation profiles will be evaluated by IHC.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05233696
|Contact: Anne Martinfirstname.lastname@example.org|
|Contact: Robyn Swingemail@example.com|
|United States, Colorado|
|University of Colorado Hospital||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Anne Martin 720-848-0657 firstname.lastname@example.org|
|Principal Investigator: Jennifer Diamond, MD|
|Sub-Investigator: Christine Fisher, MD|
|Sub-Investigator: Sana Karam, MD|
|Principal Investigator:||Jennifer Diamond, MD||University of Colorado, Denver|