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

NCT ID: NCT05112536

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-03
• Study Completion Date: 2023-03-13

Brief 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.

Conditions

Triple Negative Breast Cancer; Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trilaciclib plus chemotherapy

Trilaciclib lead-in, followed by trilaciclib plus anthracycline/cyclophosphamide, then trilaciclib plus taxane chemotherapy:

• Lead-in trilaciclib (240mg/m2) single dose monotherapy
• Trilaciclib (240mg/m2) + doxorubicin (60 mg/m2) + cyclophosphamide (600 mg/m2) + pembrolizumab (per Investigator discretion; 400mg)
• Trilaciclib (240mg/m2) + paclitaxel (80 mg/m2) + carboplatin (per Investigator discretion; AUC 1.5)

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

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

Intervention Type: DRUG

Cyclophosphamide administered IV every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.

Doxorubicin

Intervention Type: DRUG

Doxorubicin administered as an IV bolus every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered weekly for the last 12 cycles (cycles 5-16), each cycle 1 week in length.

Carboplatin (Investigator discretion)

Intervention Type: DRUG

Carboplatin, if given, is administered IV weekly at the start of paclitaxel administration, for the last 12 cycles (cycles 5-16).

Pembrolizumab (Investigator discretion)

Intervention Type: BIOLOGICAL

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

Interventions

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.

Intervention Type: DRUG

Cylophosphamide

Cyclophosphamide administered IV every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.

Intervention Type: DRUG

Doxorubicin

Doxorubicin administered as an IV bolus every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.

Intervention Type: DRUG

Paclitaxel

Paclitaxel administered weekly for the last 12 cycles (cycles 5-16), each cycle 1 week in length.

Intervention Type: 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).

Intervention Type: DRUG

Pembrolizumab (Investigator discretion)

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

Intervention Type: BIOLOGICAL

Other Intervention Names

COSELA®; G1T28; CYTOXAN®; ADRIAMYCIN®; TAXOL®; PARAPLATIN®; KEYTRUDA®

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

G1 Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cancer and Blood Specialty Clinic

Los Alamitos, California, United States

UCLA Department of Medicine - Hematology/Oncology

Santa Monica, California, United States

PIH Health

Whittier, California, United States

Nebraska Hematology-Oncology, P.C.

Lincoln, Nebraska, United States

Duke University Medical Center

Durham, North Carolina, United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

G1T28-212

Identifier Type: -

Identifier Source: org_study_id