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

Primary Purpose

Carcinoma, Ductal, Breast, Breast Cancer Female, Breast Neoplasm

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

G1T48

Palbociclib

About this trial

This is an interventional treatment trial for Carcinoma, Ductal, Breast focused on measuring Breast Cancer, Oral SERD, SERD, HER2-Negative, ER-Positive, ER+, HER2-, HER2 -ve, ER +ve, CDK 4/6 Inhibitor, Rintodestrant, G1T48

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Beverly Hills Cancer Center
Stanford Women Cancer Center
Northwestern University - Feinberg School of Medicine
University of North Carolina at Chapel Hill
Stephenson Cancer Center
Sarah Cannon Research Institute at Tennessee Oncology
Institut Jules Bordet
UZ Leuven
MHAT for Womens Health - Nadezhda OOD
ARENSIA Exploratory Medicine LLC
ARENSIA Exploratory Medicine Phase I Unit, The Institute of Oncology
VU University Medical Center
University Medical Center Groningen
Erasmus Medical Center
Spizhenko Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Part 1: Dose Escalation (G1T48)

Part 1: Food Effect Cohort (G1T48)

Part 2: Monotherapy Dose Expansion (G1T48)

Part 3: Combination Dose Expansion (G1T48+palbociclib)

Arm Description

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.

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.

Patients in Part 2 will receive G1T48 once-daily at the dose determined in Part 1.

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.

Outcomes

Primary Outcome Measures

Dose Limiting Toxicity

Recommended Phase 2 dose

G1T48 alone and in combination with palbociclib; progression-free survival (PFS)

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).

Secondary Outcome Measures

Tumor response based on RECIST, Version 1.1

G1T48 alone and in combination with palbociclib;

Effect of food on bioavailability of G1T48

Pharmacokinetics of G1T48 and metabolites: Maximum Plasma Concentration (Cmax)

Pharmacokinetics of G1T48 and metabolites: Area under Curve - plasma concentration (AUC)

Pharmacokinetics of G1T48 and metabolites: Plasma: terminal half life (T1/2)

Pharmacokinetics of G1T48 and metabolites: Plasma - Volume of distribution

Pharmacokinetics of palbociclib: Plasma - Trough concentration

Full Information

NCT ID

NCT03455270

First Posted

February 28, 2018

Last Updated

December 14, 2022

Sponsor

G1 Therapeutics, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03455270

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Completed

Study Start Date

May 9, 2018 (Actual)

Primary Completion Date

September 29, 2022 (Actual)

Study Completion Date

September 29, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

G1 Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Breast Cancer, Oral SERD, SERD, HER2-Negative, ER-Positive, ER+, HER2-, HER2 -ve, ER +ve, CDK 4/6 Inhibitor, Rintodestrant, G1T48

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

107 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Dose Escalation (G1T48)

Arm Type

Experimental

Arm Description

Arm Title

Part 1: Food Effect Cohort (G1T48)

Arm Type

Experimental

Arm Description

Arm Title

Part 2: Monotherapy Dose Expansion (G1T48)

Arm Type

Experimental

Arm Description

Patients in Part 2 will receive G1T48 once-daily at the dose determined in Part 1.

Arm Title

Part 3: Combination Dose Expansion (G1T48+palbociclib)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

G1T48

Other Intervention Name(s)

Rintodestrant

Intervention Description

oral SERD

Intervention Type

Drug

Intervention Name(s)

Palbociclib

Other Intervention Name(s)

Ibrance

Intervention Description

CDK 4/6 Inhibitor

Primary Outcome Measure Information:

Title

Dose Limiting Toxicity

Time Frame

Cycle 1 Day -3 to Cycle 1 Day 28

Title

Recommended Phase 2 dose

Description

G1T48 alone and in combination with palbociclib; progression-free survival (PFS)

Time Frame

12 months

Title

Number of Treatment Related Adverse Event, including Abnormal Laboratory Events

Description

Time Frame

21 months

Secondary Outcome Measure Information:

Title

Tumor response based on RECIST, Version 1.1

Description

G1T48 alone and in combination with palbociclib;

Time Frame

21 months

Title

Effect of food on bioavailability of G1T48

Time Frame

Part 1, Cycle 1 Day -10 to Cycle 1 Day 1.

Title

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.

Title

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.

Title

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.

Title

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.

Title

Pharmacokinetics of palbociclib: Plasma - Trough concentration

Time Frame

Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.

10. Eligibility

Sex

Female

Gender Based

Yes

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Contact

Organizational Affiliation

G1 Therapeutics, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Beverly Hills Cancer Center

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90211

Country

United States

Facility Name

Stanford Women Cancer Center

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

Facility Name

Northwestern University - Feinberg School of Medicine

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

University of North Carolina at Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599-7305

Country

United States

Facility Name

Stephenson Cancer Center

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73104

Country

United States

Facility Name

Sarah Cannon Research Institute at Tennessee Oncology

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Institut Jules Bordet

City

Brussels

ZIP/Postal Code

1000

Country

Belgium

Facility Name

UZ Leuven

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

MHAT for Womens Health - Nadezhda OOD

City

Sofia

ZIP/Postal Code

1330

Country

Bulgaria

Facility Name

ARENSIA Exploratory Medicine LLC

City

Tbilisi

ZIP/Postal Code

0112

Country

Georgia

Facility Name

ARENSIA Exploratory Medicine Phase I Unit, The Institute of Oncology

City

Chisinau

ZIP/Postal Code

2025

Country

Moldova, Republic of

Facility Name

VU University Medical Center

City

Amsterdam

ZIP/Postal Code

1081 HV

Country

Netherlands

Facility Name

University Medical Center Groningen

City

Groningen

ZIP/Postal Code

9713 GZ

Country

Netherlands

Facility Name

Erasmus Medical Center

City

Rotterdam

ZIP/Postal Code

3015 GD

Country

Netherlands

Facility Name

Spizhenko Clinic

City

Kiev

ZIP/Postal Code

08112

Country

Ukraine

12. IPD Sharing Statement

Learn more about this trial

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

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