Trilaciclib, a CDK4/6 Inhibitor, in Patients With Early-Stage Triple Negative Breast Cancer

Breast Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05112536
• Other study ID #: G1T28-212
• Status: Completed
• Phase: Phase 2
• Start date: March 3, 2022
• Est. completion date: March 13, 2023

Study information

• Verified date: December 2023
• Source: G1 Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 13, 2023
• Est. primary completion date: October 31, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Trilaciclib
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.
• Cylophosphamide
Cyclophosphamide administered IV every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.
• Doxorubicin
Doxorubicin administered as an IV bolus every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.
• Paclitaxel
Paclitaxel administered weekly for the last 12 cycles (cycles 5-16), each cycle 1 week in length.
• Carboplatin (Investigator discretion)
Carboplatin, if given, is administered IV weekly at the start of paclitaxel administration, for the last 12 cycles (cycles 5-16).

Biological:
• Pembrolizumab (Investigator discretion)
Pembrolizumab, if given, is administered IV every 6 weeks throughout the treatment phase (cycles 1, 4, 9, 15).

Locations

Country	Name	City	State
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Nebraska Hematology-Oncology, P.C.	Lincoln	Nebraska
United States	Cancer and Blood Specialty Clinic	Los Alamitos	California
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	UCLA Department of Medicine - Hematology/Oncology	Santa Monica	California
United States	PIH Health	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
G1 Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immune-based Mechanism of Action	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; post-trilaciclib ratio minus pre-trilaciclib ratio.; Research shows a correlation between immune cells, (tumor-infiltrating lymphocytes - TILs), and favorable outcomes. Both the presence of effector CD8+ T cells and the ratio of effector CD8+ T cells to immune-suppressive regulatory T cells (Treg) correlate with improved outcome and long-term survival in solid cancers. Therefore, the higher the ratio of CD8+ T cells/Tregs, the better the predicted outcome for a patient. This outcome measure is completed by looking at tumor tissue under a microscope.	Up to 8 days after lead-in trilaciclib dose
Secondary	Pathologic Complete Response (pCR) Rate	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.	Up to 26 weeks
Secondary	Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	Safety/tolerability as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Up to 28 weeks