Clinical Trials /

Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Gemcitabine and Carboplatin in Metastatic Triple Negative Breast Cancer (mTNBC)

NCT02978716

Description:

This is a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to carboplatin and gemcitabine (GC therapy) for patients with metastatic triple negative breast cancer. The study is open-label and approximately 90 patients will be randomly assigned (1:1:1 fashion) to 1 of the 3 following treatment groups: - Group 1: GC therapy (Days 1 and 8 of 21-day cycles) only (n=30) - Group 2: GC therapy (Days 1 and 8) plus trilaciclib (G1T28) on Days 1 and 8 of 21-day cycles (n=30) - Group 3: GC therapy (Days 2 and 9) plus trilaciclib (G1T28) on Days 1, 2, 8, and 9 of 21-day cycles (n=30) The study will include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Gemcitabine and Carboplatin in Metastatic Triple Negative Breast Cancer (mTNBC)
  • Official Title: Phase 2 Study of the Safety, Efficacy, and Pharmacokinetics of G1T28 in Patients With Metastatic Triple Negative Breast Cancer Receiving Gemcitabine and Carboplatin Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: G1T28-04
  • NCT ID: NCT02978716

Conditions

  • Triple-Negative Breast Neoplasms
  • Breast Neoplasm
  • Breast Cancer
  • Triple-Negative Breast Cancer

Interventions

DrugSynonymsArms
TrilaciclibG1T28, CDK 4/6 InhibitorGroup 2: Trilaciclib (G1T28) + Gemcitabine/Carboplatin
GemcitabineGroup 1: Gemcitabine/Carboplatin
CarboplatinGroup 1: Gemcitabine/Carboplatin

Purpose

This is a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to carboplatin and gemcitabine (GC therapy) for patients with metastatic triple negative breast cancer.

The study is open-label and approximately 90 patients will be randomly assigned (1:1:1 fashion) to 1 of the 3 following treatment groups:

- Group 1: GC therapy (Days 1 and 8 of 21-day cycles) only (n=30)

- Group 2: GC therapy (Days 1 and 8) plus trilaciclib (G1T28) on Days 1 and 8 of 21-day cycles (n=30)

- Group 3: GC therapy (Days 2 and 9) plus trilaciclib (G1T28) on Days 1, 2, 8, and 9 of 21-day cycles (n=30)

The study will include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Group 1: Gemcitabine/CarboplatinExperimentalGC chemotherapy (gemcitabine 1000 mg/m2 and carboplatin AUC = 2 administered IV) on Days 1 and 8 in 21-day cycles.
    • Gemcitabine
    • Carboplatin
Group 2: Trilaciclib (G1T28) + Gemcitabine/CarboplatinExperimentalTrilaciclib (G1T28) IV prior to GC chemotherapy (gemcitabine 1000 mg/m2 and carboplatin AUC = 2 administered IV) on Days 1 and 8 in 21-day cycles.
  • Trilaciclib
  • Gemcitabine
  • Carboplatin
Group 3: Trilaciclib (G1T28) + Gemcitabine/CarboplatinExperimentalTrilaciclib (G1T28) IV on Days 1, 2, 8 and 9. GC chemotherapy (gemcitabine 1000 mg/m2 and carboplatin AUC = 2 administered IV) on Days 2 and 9 in 21-day cycles.
  • Trilaciclib
  • Gemcitabine
  • Carboplatin

Eligibility Criteria

Inclusion Criteria:

- Confirmed diagnosis of HR-negative, HER2-negative (TNBC) breast cancer

- Available TNBC diagnostic tumor tissue (archived tissue allowed)

- Measurable disease as defined by RECIST, Version 1.1

- ECOG performance status 0 to 1

- Adequate organ function

- Predicted life expectancy of 3 or more months

Exclusion Criteria:

- More than 1 prior chemotherapy regimen for metastatic TNBC

- Prior treatment of metastatic breast cancer with gemcitabine, carboplatin, or cisplatin (previous adjuvant/neoadjuvant chemotherapy with carboplatin, cisplatin, or gemcitabine is allowed if ≥ 12 months have elapsed between the date of last adjuvant chemotherapy administration and first documented local or distant disease recurrence)

- Less than 12 months between date of last adjuvant chemotherapy administration (with curative intent) and first documented local or distant disease recurrence.

- Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease

- Investigational drug within 30 days of first trilaciclib (G1T28) dose

- Concurrent radiotherapy, radiotherapy within 14 days of first trilaciclib (G1T28) dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow

- Cytotoxic chemotherapy within 3 weeks of first trilaciclib (G1T28) dose

- Prior hematopoietic stem cell or bone marrow transplantation

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Treatment Related Adverse Event, including Abnormal Laboratory Events
Time Frame:18 months
Safety Issue:
Description:All AEs, including clinical laboratory, vitals signs, physical examinations and ECGs will be analyzed in all patients receiving study drug from from the signing of the informed consent until 30 days after the last dose of study medication up to 18 months

Secondary Outcome Measures

Measure:Tumor response based on RECIST, Version 1.1
Time Frame:18 months
Safety Issue:
Description:
Measure:Progression free survival (PFS)
Time Frame:27 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:36 months
Safety Issue:
Description:
Measure:Hematologic parameters
Time Frame:18 months
Safety Issue:
Description:Number of patients with treatment related abnormal laboratory assessments. Laboratory toxicities will be assessed using NCI CTCAE, Version 4.03
Measure:Pharmacokinetics of Trilaciclib (G1T28), Carboplatin and Gemcitabine: Maximum Plasma Concentration (Cmax)
Time Frame:24 hours
Safety Issue:
Description:The observed peak plasma concentration determined from the plasma (Cmax)
Measure:Pharmacokinetics of Trilaciclib (G1T28), Carboplatin and Gemcitabine: Area under Curve - plasma concentration (AUC)
Time Frame:24 hours
Safety Issue:
Description:Area under the plasma concentration-time curve (AUC)
Measure:Pharmacokinetics of Trilaciclib (G1T28), Carboplatin and Gemcitabine: Plasma: terminal half life (T1/2)
Time Frame:24 hours
Safety Issue:
Description:Plasma- terminal half life (T1/2)
Measure:Pharmacokinetics of Trilaciclib (G1T28), Carboplatin and Gemcitabine: Plasma - Volume of distribution
Time Frame:24 hours
Safety Issue:
Description:Volume of distribution in the terminal elimination phase (Vz)
Measure:Incidence of chemotherapy dose reductions
Time Frame:18 months
Safety Issue:
Description:
Measure:Incidence of dose interruptions overall
Time Frame:18 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:G1 Therapeutics, Inc.

Trial Keywords

  • Breast Cancer
  • CDK 4/6 Inhibitor
  • Triple Negative Breast Cancer

Last Updated

January 12, 2017