G1T48, an Oral SERD, Alone and in Combination With Palbociclib in ER-Positive, HER2-Negative Advanced Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03455270
• Other study ID #: G1T48-01
• Secondary ID: 2017-004502-17
• Status: Completed
• Phase: Phase 1
• Start date: May 9, 2018
• Est. completion date: September 29, 2022

Study information

• Verified date: December 2022
• Source: G1 Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: September 29, 2022
• Est. primary completion date: September 29, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• For Part 1, postmenopausal women only

• For Parts 2 and 3, any menopausal status

• Confirmed diagnosis of ER-positive, HER2-negative advanced breast cancer, not amenable to curative therapy

• For Part 1, prior treatment with less than 4 prior lines of chemotherapy

• For Part 2, prior treatment with less than 2 prior line of chemotherapy

• For Part 3, prior treatment with no more than 1 prior line of chemotherapy

• For Parts 1 and 2, prior treatment with less than 4 prior endocrine therapies for metastatic breast cancer

• For Part 3, prior treatment with no more than 1 prior line of endocrine therapies for metastatic breast cancer

• For Parts 1 and 2, patients must satisfy 1 of the following criteria for prior therapy:

• Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor

• Progressed after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer

• For Part 3, patients must satisfy 1 of the following criteria for prior therapy:

• Received = 24 months of endocrine therapy in the adjuvant setting prior to recurrence or progression

• Received = 6 months of endocrine therapy in the advanced/metastatic setting prior to progression

• For Part 1, evaluable or measurable disease

• For Parts 2 and 3, evaluable (approximately 25%) or measurable disease (approximately 75%) as defined by RECIST, Version 1.1 including bone-only disease

• ECOG performance status 0 to 1

• Adequate organ function

Exclusion Criteria:

• For Part 3, prior treatment with CDK4/6 inhibitor, investigational oral SERDs or SERCAs in any setting

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

• Anticancer therapy within 14 days of first G1T48 dose or within 28 days for antibody-based therapy

• Concurrent radiotherapy, radiotherapy within 14 days of first G1T48 dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow

• Prior hematopoietic stem cell or bone marrow transplantation

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Cancer
• Breast Cancer Female
• Breast Neoplasm
• Breast Neoplasms
• Carcinoma, Ductal
• Carcinoma, Ductal, Breast
• Metastatic Breast Cancer
• Stage IV Breast Cancer

Intervention

Drug:
• G1T48
oral SERD
• Palbociclib
CDK 4/6 Inhibitor

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Brussels
Belgium	UZ Leuven	Leuven
Bulgaria	MHAT for Womens Health - Nadezhda OOD	Sofia
Georgia	ARENSIA Exploratory Medicine LLC	Tbilisi
Moldova, Republic of	ARENSIA Exploratory Medicine Phase I Unit, The Institute of Oncology	Chisinau
Netherlands	VU University Medical Center	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Erasmus Medical Center	Rotterdam
Ukraine	Spizhenko Clinic	Kiev
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University - Feinberg School of Medicine	Chicago	Illinois
United States	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Stanford Women Cancer Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
G1 Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Georgia,  Moldova, Republic of,  Netherlands,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity		Cycle 1 Day -3 to Cycle 1 Day 28
Primary	Recommended Phase 2 dose	G1T48 alone and in combination with palbociclib; progression-free survival (PFS)	12 months
Primary	Number of Treatment Related Adverse Event, including Abnormal Laboratory Events	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).	21 months
Secondary	Tumor response based on RECIST, Version 1.1	G1T48 alone and in combination with palbociclib;	21 months
Secondary	Effect of food on bioavailability of G1T48		Part 1, Cycle 1 Day -10 to Cycle 1 Day 1.
Secondary	Pharmacokinetics of G1T48 and metabolites: Maximum Plasma Concentration (Cmax)		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.
Secondary	Pharmacokinetics of G1T48 and metabolites: Area under Curve - plasma concentration (AUC)		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.
Secondary	Pharmacokinetics of G1T48 and metabolites: Plasma: terminal half life (T1/2)		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.
Secondary	Pharmacokinetics of G1T48 and metabolites: Plasma - Volume of distribution		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.
Secondary	Pharmacokinetics of palbociclib: Plasma - Trough concentration		Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.