ACTIVE_NOT_RECRUITING

Phase II Trial of Trilaciclib, Pembrolizumab, Gemcitabine and Carboplatin in Metastatic Triple-Negative Breast Cancer

Conditions

Metastatic Triple-Negative Breast Cancer Breast-Female Breast-Male Triple-Negative Breast Cancer Metastatic Locally advanced unresectable

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The goal of this phase II study is to test the combination of trilaciclib, pembrolizumab, gemcitabine, and carboplatin in locally advanced unresectable or metastatic triple-negative breast cancer. The main questions it aims to answer are: * to evaluate the anti-cancer efficacy (assess how well it works) * to evaluate the safety and tolerability (how well the body can handle the treatment) of this combination of anti-cancer therapy

Official Title

ToPCourT: A Phase II Trial of Trilaciclib, Pembrolizumab, Gemcitabine and Carboplatin in Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (TNBC)

Quick Facts

Study Start:2024-01-10

Study Completion:2027-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06027268

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Written informed consent and HIPAA authorization for release of personal health information signed by the patient 2. Male or female with locally advanced unresectable or metastatic TNBC 3. Age ≥ 18 years at the time of consent 4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 evaluated within 28 days prior to day 1 of study treatment 5. Histological or cytological confirmation of estrogen negative and progesterone negative tumor, defined as \< 10% staining on immunohistochemistry (IHC) and human epidermal growth factor receptor type 2 (HER2)-negative, defined as HER 2 IHC 0 or 1+ or IHC 2+ with no amplification. Patients may be enrolled regardless of their PD-L1 (programmed death ligand-1) status. 6. Measurable disease according to response evaluation criteria in solid tumors 7. Demonstrate adequate organ function 8. Female patients: All females of childbearing potential must have a negative serum β-human chorionic gonadotropin (hCG) test result at Screening and negative serum or urine pregnancy test results within 72 hours prior to day 1 of study treatment. 9. Subject agrees to use contraception 10. As determined by the enrolling physician, the ability of the subject to understand and comply with study procedures for the entire length of the study 11. Tumor tissue: Willing to provide tumor tissue for research purposes 12. Subject has a life expectancy of ≥ 12 weeks	1. More than 3 prior lines of chemotherapy for locally advanced unresectable or triple-negative metastatic disease 2. Prior therapy with the concurrent combination of gemcitabine and carboplatin in the metastatic setting 3. Active, symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis or CNS metastases that are progressing on screening magnetic resonance imaging (MRI) brain. 4. Prior systemic anti-cancer therapy within 3 weeks, prior stereotactic radiotherapy within 1 week, and radiation within 2 weeks of day 1 of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation to non-CNS disease. 5. Major surgery, defined by the investigator's discretion, within 3 weeks of day 1 of study treatment 6. Not recovered from all reversible acute toxic effects of prior therapy, including non-hematologic toxicities related to prior systemic therapy to ≤ Grade 1. Participants with less than Grade 2 neuropathy or alopecia of any grade are an exception 7. Active infection requiring systemic therapy 8. Pregnant or breastfeeding 9. Participants previously diagnosed with an additional malignancy must be disease-free for at least five years prior to enrollment. Exceptions include basal cell or squamous cell skin cancer and in situ cervical or bladder cancer. 10. Treatment with any investigational drug within 30 days or at least 5 half-lives, whichever is longer, prior to day 1 of study treatment 11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled symptomatic congestive heart failure (Class III or IV as defined by the New York Heart Association (NYHA) functional classification system), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations/substance abuse that would limit compliance with study requirements as determined by the investigator 12. Known history of stroke or cerebrovascular event within 6 months prior to the day 1 of study treatment 13. Known hypersensitivity to carboplatin or other platinum-containing compounds, gemcitabine, mannitol, or pembrolizumab 14. History of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids or current ILD/ pneumonitis. 15. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) prior to day 1 of study treatment. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed 16. Prior hematopoietic stem cell or bone marrow transplant or allogenic tissue/solid organ transplant 17. Has a known history of Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome (AIDS) 18. Has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive). 19. Has known active hepatitis C (e.g., hepatitis C virus (HCV) ribonucleic acid (RNA) \[qualitative\] is detected). 20. Receipt of a live, attenuated vaccine within 30 days prior to day 1 of study treatment or anticipation that such a live, attenuated vaccine will be required during the study treatment period. Administration of killed vaccines is allowed. Exception: Monkeypox vaccine may be given if there are at least 3 days between the vaccine and initiation of study treatment.

Inclusion Criteria

Exclusion Criteria

1. Written informed consent and HIPAA authorization for release of personal health information signed by the patient
2. Male or female with locally advanced unresectable or metastatic TNBC
3. Age ≥ 18 years at the time of consent
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 evaluated within 28 days prior to day 1 of study treatment
5. Histological or cytological confirmation of estrogen negative and progesterone negative tumor, defined as \< 10% staining on immunohistochemistry (IHC) and human epidermal growth factor receptor type 2 (HER2)-negative, defined as HER 2 IHC 0 or 1+ or IHC 2+ with no amplification. Patients may be enrolled regardless of their PD-L1 (programmed death ligand-1) status.
6. Measurable disease according to response evaluation criteria in solid tumors
7. Demonstrate adequate organ function
8. Female patients: All females of childbearing potential must have a negative serum β-human chorionic gonadotropin (hCG) test result at Screening and negative serum or urine pregnancy test results within 72 hours prior to day 1 of study treatment.
9. Subject agrees to use contraception
10. As determined by the enrolling physician, the ability of the subject to understand and comply with study procedures for the entire length of the study
11. Tumor tissue: Willing to provide tumor tissue for research purposes
12. Subject has a life expectancy of ≥ 12 weeks

1. More than 3 prior lines of chemotherapy for locally advanced unresectable or triple-negative metastatic disease
2. Prior therapy with the concurrent combination of gemcitabine and carboplatin in the metastatic setting
3. Active, symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis or CNS metastases that are progressing on screening magnetic resonance imaging (MRI) brain.
4. Prior systemic anti-cancer therapy within 3 weeks, prior stereotactic radiotherapy within 1 week, and radiation within 2 weeks of day 1 of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation to non-CNS disease.
5. Major surgery, defined by the investigator's discretion, within 3 weeks of day 1 of study treatment
6. Not recovered from all reversible acute toxic effects of prior therapy, including non-hematologic toxicities related to prior systemic therapy to ≤ Grade 1. Participants with less than Grade 2 neuropathy or alopecia of any grade are an exception
7. Active infection requiring systemic therapy
8. Pregnant or breastfeeding
9. Participants previously diagnosed with an additional malignancy must be disease-free for at least five years prior to enrollment. Exceptions include basal cell or squamous cell skin cancer and in situ cervical or bladder cancer.
10. Treatment with any investigational drug within 30 days or at least 5 half-lives, whichever is longer, prior to day 1 of study treatment
11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled symptomatic congestive heart failure (Class III or IV as defined by the New York Heart Association (NYHA) functional classification system), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations/substance abuse that would limit compliance with study requirements as determined by the investigator
12. Known history of stroke or cerebrovascular event within 6 months prior to the day 1 of study treatment
13. Known hypersensitivity to carboplatin or other platinum-containing compounds, gemcitabine, mannitol, or pembrolizumab
14. History of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids or current ILD/ pneumonitis.
15. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) prior to day 1 of study treatment. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
16. Prior hematopoietic stem cell or bone marrow transplant or allogenic tissue/solid organ transplant
17. Has a known history of Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
18. Has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive).
19. Has known active hepatitis C (e.g., hepatitis C virus (HCV) ribonucleic acid (RNA) \[qualitative\] is detected).
20. Receipt of a live, attenuated vaccine within 30 days prior to day 1 of study treatment or anticipation that such a live, attenuated vaccine will be required during the study treatment period. Administration of killed vaccines is allowed. Exception: Monkeypox vaccine may be given if there are at least 3 days between the vaccine and initiation of study treatment.

Contacts and Locations

Principal Investigator

Antoinette Tan, MD

PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Study Locations (Sites)

Levine Cancer Institute

Charlotte, North Carolina, 28204

United States

Collaborators and Investigators

Sponsor: Wake Forest University Health Sciences

Antoinette Tan, MD, PRINCIPAL_INVESTIGATOR, Wake Forest University Health Sciences

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-01-10

Study Completion Date2027-03

Study Record Updates

Study Start Date2024-01-10

Study Completion Date2027-03

Terms related to this study

Keywords Provided by Researchers

Breast-Female
Breast-Male
Triple-Negative Breast Cancer
Metastatic
Locally advanced unresectable

Additional Relevant MeSH Terms

Metastatic Triple-Negative Breast Cancer