Trilaciclib, a CDK4/6 Inhibitor, in Patients With Early-Stage Triple Negative Breast Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT05112536|
Recruitment Status : Recruiting
First Posted : November 9, 2021
Last Update Posted : June 9, 2022
The purpose of this study is to evaluate the mechanism of action, as well as the safety and efficacy of trilaciclib in combination with standard of care treatment in the neoadjuvant setting of early-stage triple negative breast cancer (TNBC).
This study will have four phases: 1) Screening Phase, 2) Trilaciclib Lead-In Phase, 3) Treatment Phase, and 4) Surgery and Follow-Up Phase. After a screening phase of up to 21 day, each participant will receive trilaciclib single-dose monotherapy during the lead-in phase, followed by a tumor biopsy. During the treatment phase, each participant will receive trilaciclib with standard of care chemotherapy. Immunotherapy may be included during the treatment phase, per standard of care. 3-5 weeks following conclusion of the treatment phase, each participant will undergo definitive surgery. A 30-day Safety Follow-up Visit will occur 30 days after the last dose of trilaciclib and an End of Study Visit will occur within 14 days after definitive surgery.
|Condition or disease||Intervention/treatment||Phase|
|Triple Negative Breast Cancer Breast Cancer||Drug: Trilaciclib Drug: Cylophosphamide Drug: Doxorubicin Drug: Paclitaxel Drug: Carboplatin (Investigator discretion) Biological: Pembrolizumab (Investigator discretion)||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2, Open-Label, Single-Arm Study of Single-Dose Lead-In and Neoadjuvant Trilaciclib and Chemotherapy in Patients With Early-Stage Triple Negative Breast Cancer (TNBC)|
|Actual Study Start Date :||November 19, 2021|
|Estimated Primary Completion Date :||August 20, 2022|
|Estimated Study Completion Date :||February 24, 2023|
Experimental: Trilaciclib plus chemotherapy
Trilaciclib lead-in, followed by trilaciclib plus anthracycline/cyclophosphamide, then trilaciclib plus taxane chemotherapy:
Trilaciclib is administered IV as monotherapy during the lead-in phase and administered prior to chemotherapy on each day chemotherapy is administered during the treatment phase.
Cyclophosphamide administered IV every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.
Other Name: CYTOXAN®
Doxorubicin administered as an IV bolus every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.
Other Name: ADRIAMYCIN®
Paclitaxel administered weekly for the last 12 cycles (cycles 5-16), each cycle 1 week in length.
Other Name: TAXOL®
Drug: Carboplatin (Investigator discretion)
Carboplatin, if given, is administered IV weekly at the start of paclitaxel administration, for the last 12 cycles (cycles 5-16).
Other Name: PARAPLATIN®
Biological: Pembrolizumab (Investigator discretion)
Pembrolizumab, if given, is administered IV every 6 weeks throughout the treatment phase (cycles 1, 4, 9, 15).
Other Name: KEYTRUDA®
- Immune-based mechanism of action [ Time Frame: Up to 8 days ]Evaluated 7 days after a single-dose of trilaciclib, measured by the change in CD8 T cells/regulatory T cells (Treg) ratio in tumor tissue.
- Pathologic Complete Response (pCR) rate [ Time Frame: Up to 26 weeks ]Rate of pCR using the definition of ypT0/Tis ypN0 (i.e., no invasive residual tumor in breast or nodes; noninvasive breast residuals allowed) as assessed by the local pathologist.
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Up to 28 weeks ]Safety/tolerability as per CTCAE version 5.0
- Intratumoral immune profile characterization following trilaciclib [ Time Frame: Up to 26 weeks ]Characterization of molecular and immune changes based on CD8+ T cell and Treg infiltration, quantified by RNA profiling of tumor tissue before study treatment, during study treatment, and at definitive surgery.
- Kinetics of the immune response in peripheral blood [ Time Frame: Up to 26 weeks ]Longitudinal immune changes in peripheral blood, measured by frequency of immune subsets and profiling of activation, maturation, and exhaustion status.
- Kinetics of T cell function and polyfunctionality [ Time Frame: Up to 26 weeks ]Ex-vivo measurement of cytokine production to determine T cell function and polyfunctionality.
- Molecular biomarkers for clinical responsiveness [ Time Frame: Up to 26 weeks ]pCR in patients by gene signatures determined in the tumor at baseline.
- CDK4/6 dependence for clinical responsiveness [ Time Frame: Up to 26 weeks ]pCR in patients by subgroups according to CDK4/6 dependence signatures.
- PD-L1 status and clinical responsiveness [ Time Frame: Up to 26 weeks ]pCR in patients by subgroups according to PD-L1 status, as measured by IHC.
- Immune response and clinical responsiveness [ Time Frame: Up to 26 weeks ]pCR in patients by frequency of immune subsets, immunological markers, and cytokines.
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): NCT05112536
|Contact: G1 Therapeutics, Inc. Clinical Contactfirstname.lastname@example.org|
|Contact: G1 Therapeutics, Inc. Clinical Contact Study Director|
|United States, California|
|Providence Medical Foundation||Recruiting|
|Fullerton, California, United States, 92835|
|Contact: Blanca Sanchez Blanca.email@example.com|
|Contact: Teresa Olea Teresa.Olea@stjoe.org|
|Principal Investigator: William Lawler, MD|
|Cancer and Blood Specialty Clinic||Recruiting|
|Los Alamitos, California, United States, 90720|
|Contact: Mimi Washington firstname.lastname@example.org|
|Principal Investigator: Vu Phan, MD|
|UCLA Department of Medicine - Hematology/Oncology||Recruiting|
|Santa Monica, California, United States, 90404|
|Contact: Monica Rocha MPRocha@mednet.ucla.edu|
|Contact: Hiromi Yagi HYagi@mednet.ucla.edu|
|Principal Investigator: Sara Hurvitz, MD|
|Whittier, California, United States, 90602|
|Contact: Gayle Madden-Mathes, RN 562-698-0811 ext 13488 Gayle.MaddenMathes@pihhealth.org|
|Contact: Rosie Drulias, RN 562-698-0811 ext 12930 Rosie.Drulias@pihhealth.org|
|Principal Investigator: Lisa Wang, MD|
|United States, Florida|
|Orlando Health Cancer Institute||Recruiting|
|Orlando, Florida, United States, 32806|
|Contact: Jennifer Durand Jennifer.Durand@orlandohealth.com|
|Contact: Janice Porter Janice.Porter@orlandohealth.com|
|Principal Investigator: Regan Rostorfer, MD|
|United States, Nebraska|
|Nebraska Hematology-Oncology, P.C.||Recruiting|
|Lincoln, Nebraska, United States, 68506|
|Contact: Vienna Lionberger email@example.com|
|Contact: Kent Disney firstname.lastname@example.org|
|Principal Investigator: Kailash Mosalpuria, MD|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: Michelle Parks Michelle.email@example.com|
|Principal Investigator: Jeremy Force, DO|
|United States, Texas|
|Texas Oncology - Austin Central||Recruiting|
|Austin, Texas, United States, 78731|
|Contact: Michelle L. Owens firstname.lastname@example.org|
|Principal Investigator: Debra Patt, MD|
|Texas Oncology - Baylor Charles A. Sammons Cancer Center||Recruiting|
|Dallas, Texas, United States, 75246|
|Contact: Jonathan B. Huntzinger email@example.com|
|Principal Investigator: Joyce A. O'Shaughnessy, MD|
|United States, Virginia|
|Virginia Oncology Associates||Recruiting|
|Norfolk, Virginia, United States, 23502|
|Contact: Angel Kidd firstname.lastname@example.org|
|Principal Investigator: Michael A. Danso, MD|