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.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Triple-Negative Breast Neoplasms; Breast Neoplasm; Breast Cancer; Triple-Negative Breast Cancer	Drug: Trilaciclib; Drug: Gemcitabine; Drug: Carboplatin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 7, 2017
• Actual Primary Completion Date: July 30, 2018
• Estimated Study Completion Date: June 2020

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; 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.	Drug: Trilaciclib; G1T28; Other Names: G1T28; CDK 4/6 Inhibitor; Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; 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.	Drug: Trilaciclib; G1T28; Other Names: G1T28; CDK 4/6 Inhibitor; Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; Carboplatin

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Tumor response based on RECIST, Version 1.1 [ Time Frame: 18 months ]
2. Progression free survival (PFS) [ Time Frame: 27 months ]
3. Overall survival (OS) [ Time Frame: 36 months ]
4. 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
5. 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)
6. 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)
7. Pharmacokinetics of Trilaciclib (G1T28), Carboplatin and Gemcitabine: Plasma: terminal half life (T1/2) [ Time Frame: 24 hours ]
   Plasma- terminal half life (T1/2)
8. Pharmacokinetics of Trilaciclib (G1T28), Carboplatin and Gemcitabine: Plasma - Volume of distribution [ Time Frame: 24 hours ]
   Volume of distribution in the terminal elimination phase (Vz)
9. Incidence of chemotherapy dose reductions [ Time Frame: 18 months ]
10. Incidence of dose interruptions overall [ Time Frame: 18 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

  Show 54 Study Locations

Sponsors and Collaborators

G1 Therapeutics, Inc.

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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]

• Responsible Party: G1 Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02978716 History of Changes
• Other Study ID Numbers: G1T28-04; 2016-004466-26 ( EudraCT Number )
• First Posted: December 1, 2016
• Last Update Posted: July 26, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by G1 Therapeutics, Inc.:

Breast Cancer; CDK 4/6 Inhibitor; Triple Negative Breast Cancer; Metastatic

Additional relevant MeSH terms:

Breast Neoplasms; Triple Negative Breast Neoplasms; Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Gemcitabine; Carboplatin; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs