Trilaciclib, a CDK4/6 Inhibitor, in Patients With Early-Stage Triple Negative Breast Cancer
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|ClinicalTrials.gov Identifier: NCT05112536|
Recruitment Status : Completed
First Posted : November 9, 2021
Last Update Posted : March 24, 2023
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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)|
|Actual Enrollment :||24 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|
|Actual Primary Completion Date :||October 31, 2022|
|Actual Study Completion Date :||March 13, 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Gender Based Eligibility:||Yes|
|Accepts Healthy Volunteers:||No|
- Suitability of therapy and patient intends to undergo curative surgery
- Documented diagnosis of estrogen receptor (ER)-negative and progesterone receptor (PR)-negative tumor
- Primary tumor ≥ 1.5 cm with any nodal status
- Provide archival tissue for the baseline tissue sample
- ECOG performance status of 0 or 1
- Demonstrates adequate organ function
- Research tumor biopsies including at least one on-treatment biopsy (and additional biopsy at baseline, if required)
- Participants of child bearing potential must be willing to use 2 forms of contraception during the study and for 6 months following study treatment
- Prior systemic therapies or radiation for current breast cancer
- History of invasive malignancy ≤3 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
- History of breast cancer including ipsilateral ductal carcinoma in situ (DCIS) treated with radiotherapy at any time
- Previous exposure to doxorubicin of more than 200 mg/m2 (as lifetime exposure to doxorubicin is not to exceed 450 mg/m2)
For patients who will receive pembrolizumab:
- History of active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is not considered a form of systemic treatment
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drugs
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Known history of active tuberculosis (Bacillus Tuberculosis)
- History of severe hepatic impairment
- Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure (Class II-IV as defined by the New York Heart Association [NYHA] functional classification system)
- Known history of stroke, cerebrovascular accident, severe/unstable angina, myocardial infarction, or coronary angioplasty/stenting/bypass grafting within 6 months prior to enrollment
- Known serious active infection (e.g., human immunodeficiency virus [HIV], hepatitis B or C, tuberculosis).
- Women who are pregnant or breastfeeding
- Participation in other studies involving active treatment with investigational drug(s)
- Prior hematopoietic stem cell or bone marrow transplantation
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
|United States, California|
|Cancer and Blood Specialty Clinic|
|Los Alamitos, California, United States, 90720|
|UCLA Department of Medicine - Hematology/Oncology|
|Santa Monica, California, United States, 90404|
|Whittier, California, United States, 90602|
|United States, Nebraska|
|Nebraska Hematology-Oncology, P.C.|
|Lincoln, Nebraska, United States, 68506|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Texas|
|Texas Oncology - Baylor Charles A. Sammons Cancer Center|
|Dallas, Texas, United States, 75246|
|United States, Virginia|
|Virginia Oncology Associates|
|Norfolk, Virginia, United States, 23502|
|Responsible Party:||G1 Therapeutics, Inc.|
|Other Study ID Numbers:||
|First Posted:||November 9, 2021 Key Record Dates|
|Last Update Posted:||March 24, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Triple Negative Breast Cancer
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Breast cancer surgery
Triple Negative Breast Neoplasms
Neoplasms by Site
Antineoplastic Agents, Phytogenic
Molecular Mechanisms of Pharmacological Action
Topoisomerase II Inhibitors
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors