G1T48, an Oral SERD, Alone and in Combination With Palbociclib in ER-Positive, HER2-Negative Advanced Breast Cancer
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|ClinicalTrials.gov Identifier: NCT03455270|
Recruitment Status : Active, not recruiting
First Posted : March 6, 2018
Last Update Posted : February 26, 2020
This is a study to investigate the potential clinical benefit of G1T48 as an oral selective estrogen receptor degrader (SERD) alone and in combination with palbociclib, a cyclin dependent kinase 4/6 (CDK 4/6) inhibitor, in patients with estrogen receptor-positive, HER2-negative metastatic breast cancer.
The study is an open-label design, consisting of 3 parts: dose-finding portion including food effect (Part 1), G1T48 monotherapy expansion portion (Part 2), and G1T48 in combination with palbociclib expansion portion (Part 3). All parts 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. Approximately, 184 patients may be enrolled in the study.
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Ductal, Breast Breast Cancer Female Breast Neoplasm Breast Cancer Metastatic Breast Cancer Advanced Breast Cancer Stage IV Breast Cancer||Drug: G1T48 Drug: Palbociclib||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||184 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Ascending Doses of G1T48 Alone and in Combination With Palbociclib in Women With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer|
|Actual Study Start Date :||May 9, 2018|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||March 2024|
Experimental: Part 1: Dose Escalation (G1T48)
Patients in Part 1 will receive a single oral dose of G1T48 on Cycle 1 Day -3 and will begin once-daily dosing on Cycle 1 Day 1.
The initial dose cohort shall receive an identified starting dose and subsequent cohorts shall receive higher doses based on the safety and PK data obtained from the previous dose levels.
Experimental: Part 1: Food Effect Cohort (G1T48)
In Part 1, additional G1T48 cohort(s) of 8 patients may be enrolled to assess the effect of different fat content meals (eg, high fat, moderate fat, or low-fat) on the rate and extent of the absorption of G1T48.
Patients will receive a single oral dose of G1T48 on Cycle 1 Day -10 and on Cycle 1 Day -3. Patients will begin G1T48 once-daily dosing on Cycle 1 Day 1.
Experimental: Part 2: Monotherapy Dose Expansion (G1T48)
Patients in Part 2 will receive G1T48 once-daily at the dose determined in Part 1.
Experimental: Part 3: Combination Dose Expansion (G1T48+palbociclib)
Patients in Part 3 will receive G1T48 once-daily at the dose determined in Part 2 in combination with palbociclib once-daily on Days 1 to 21 of each 28-day cycle.
CDK 4/6 Inhibitor
Other Name: Ibrance
- Dose Limiting Toxicity [ Time Frame: Cycle 1 Day -3 to Cycle 1 Day 28 ]
- Recommended Phase 2 dose [ Time Frame: 12 months ]G1T48 alone and in combination with palbociclib; progression-free survival (PFS)
- Number of Treatment Related Adverse Event, including Abnormal Laboratory Events [ Time Frame: 21 months ]All AEs, including clinical laboratory, vitals signs, physical examinations and ECGs will be analyzed in all patients receiving study drug(s) from the signing of the informed consent until 30 days after the last dose of study medication(s).
- Tumor response based on RECIST, Version 1.1 [ Time Frame: 21 months ]G1T48 alone and in combination with palbociclib;
- Effect of food on bioavailability of G1T48 [ Time Frame: Part 1, Cycle 1 Day -10 to Cycle 1 Day 1. ]
- Pharmacokinetics of G1T48 and metabolites: Maximum Plasma Concentration (Cmax) [ Time Frame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1. ]
- Pharmacokinetics of G1T48 and metabolites: Area under Curve - plasma concentration (AUC) [ Time Frame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1. ]
- Pharmacokinetics of G1T48 and metabolites: Plasma: terminal half life (T1/2) [ Time Frame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1. ]
- Pharmacokinetics of G1T48 and metabolites: Plasma - Volume of distribution [ Time Frame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1. ]
- Pharmacokinetics of palbociclib: Plasma - Trough concentration [ Time Frame: Part 3, Cycle 2 Day 1 to Cycle 3 Day 1. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03455270
|United States, California|
|Beverly Hills Cancer Center|
|Beverly Hills, California, United States, 90211|
|Stanford Women Cancer Center|
|Stanford, California, United States, 94305|
|United States, Florida|
|Florida Cancer Specialists & Research Institute|
|Saint Petersburg, Florida, United States, 33705|
|United States, Illinois|
|Northwestern University - Feinberg School of Medicine|
|Chicago, Illinois, United States, 60611|
|United States, North Carolina|
|University of North Carolina at Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599-7305|
|United States, Oklahoma|
|Stephenson Cancer Center|
|Oklahoma City, Oklahoma, United States, 73104|
|United States, Tennessee|
|Sarah Cannon Research Institute at Tennessee Oncology|
|Nashville, Tennessee, United States, 37203|
|Institut Jules Bordet|
|Brussels, Belgium, 1000|
|Leuven, Belgium, 3000|
|ARENSIA Exploratory Medicine LLC|
|Tbilisi, Georgia, 0112|
|Moldova, Republic of|
|ARENSIA Exploratory Medicine Phase I Unit, The Institute of Oncology|
|Chisinau, Moldova, Republic of, 2025|
|VU University Medical Center|
|Amsterdam, Netherlands, 1081 HV|
|University Medical Center Groningen|
|Groningen, Netherlands, 9713 GZ|
|Erasmus Medical Center|
|Rotterdam, Netherlands, 3015 GD|
|Study Director:||Clinical Contact||G1 Therapeutics, Inc.|