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

• ClinicalTrials.gov Identifier: NCT02978716
• Recruitment Status: Active, not recruiting
• First Posted: December 1, 2016
• Last Update Posted: July 26, 2019
• Sponsor: G1 Therapeutics, Inc.
• Information provided by (Responsible Party): G1 Therapeutics, Inc.

Tracking Information

• First Submitted Date: November 18, 2016
• First Posted Date: December 1, 2016
• Last Update Posted Date: July 26, 2019
• Actual Study Start Date: February 7, 2017
• Actual Primary Completion Date: July 30, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 28, 2016)

Number of Treatment Related Adverse Event, including Abnormal Laboratory Events [ Time Frame: 18 months ]

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

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02978716 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 7, 2016)

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

Original Secondary Outcome Measures (submitted: November 28, 2016)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

Brief Summary

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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Trilaciclib
  G1T28
  Other Names:

  • G1T28
  • CDK 4/6 Inhibitor
• Drug: Gemcitabine
  Gemcitabine
• Drug: Carboplatin
  Carboplatin

Study Arms

• Experimental: Group 1: Gemcitabine/Carboplatin
  GC chemotherapy (gemcitabine 1000 mg/m2 and carboplatin AUC = 2 administered IV) on Days 1 and 8 in 21-day cycles.
  Interventions:

  • Drug: Gemcitabine
  • Drug: Carboplatin
• Experimental: Group 2: Trilaciclib (G1T28) + Gemcitabine/Carboplatin
  Trilaciclib (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.
  Interventions:

  • Drug: Trilaciclib
  • Drug: Gemcitabine
  • Drug: Carboplatin
• Experimental: Group 3: Trilaciclib (G1T28) + Gemcitabine/Carboplatin
  Trilaciclib (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.
  Interventions:

  • Drug: Trilaciclib
  • Drug: Gemcitabine
  • Drug: Carboplatin

• Publications *: Tan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnović Ž, Vasev N, Ma L, Richards DA, Wilks ST, Milenković D, Yang Z, Antal JM, Morris SR, O'Shaughnessy J. Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 2019 Sep 27. pii: S1470-2045(19)30616-3. doi: 10.1016/S1470-2045(19)30616-3. [Epub ahead of print]

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 23, 2018): 102
• Original Estimated Enrollment (submitted: November 28, 2016): 90
• Estimated Study Completion Date: June 2020
• Actual Primary Completion Date: July 30, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Confirmed diagnosis of HR-negative, HER2-negative (locally recurrent or metastatic TNBC) breast cancer
• Available TNBC diagnostic tumor tissue (archived tissue allowed)
• Evaluable disease
• ECOG performance status 0 to 1
• Adequate organ function
• Predicted life expectancy of 3 or more months

Exclusion Criteria:

• More than 2 prior chemotherapy regimens for locally recurrent or metastatic TNBC. If ≥ 12 months have elapsed between the date of last adjuvant/neoadjuvant chemotherapy administration and first documented local or distant disease recurrence the therapy will not be considered a line of therapy in the locally recurrent or metastatic TNBC setting.
• CNS metastases or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
• Investigational drug within 30 days of first trilaciclib (G1T28) dose
• Concurrent radiotherapy, radiotherapy within 14 days of first trilaciclib (G1T28) dose
• Cytotoxic chemotherapy within 3 weeks of first trilaciclib (G1T28) dose
• Prior hematopoietic stem cell or bone marrow transplantation

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Bulgaria, Croatia, North Macedonia, Serbia, Slovakia, Slovenia, United States
• Removed Location Countries: Macedonia, The Former Yugoslav Republic of, United Kingdom

Administrative Information

• NCT Number: NCT02978716
• Other Study ID Numbers: G1T28-04; 2016-004466-26 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: G1 Therapeutics, Inc.
• Study Sponsor: G1 Therapeutics, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Contact; G1 Therapeutics, Inc.

• PRS Account: G1 Therapeutics, Inc.
• Verification Date: July 2019