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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03455270
Recruitment Status : Active, not recruiting
First Posted : March 6, 2018
Last Update Posted : February 26, 2020
Sponsor:
Information provided by (Responsible Party):
G1 Therapeutics, Inc.

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.


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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 184 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Palbociclib

Arm Intervention/treatment
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.

Drug: G1T48
oral SERD

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.

Drug: G1T48
oral SERD

Experimental: Part 2: Monotherapy Dose Expansion (G1T48)
Patients in Part 2 will receive G1T48 once-daily at the dose determined in Part 1.
Drug: G1T48
oral SERD

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.
Drug: G1T48
oral SERD

Drug: Palbociclib
CDK 4/6 Inhibitor
Other Name: Ibrance




Primary Outcome Measures :
  1. Dose Limiting Toxicity [ Time Frame: Cycle 1 Day -3 to Cycle 1 Day 28 ]
  2. Recommended Phase 2 dose [ Time Frame: 12 months ]
    G1T48 alone and in combination with palbociclib; progression-free survival (PFS)

  3. 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).


Secondary Outcome Measures :
  1. Tumor response based on RECIST, Version 1.1 [ Time Frame: 21 months ]
    G1T48 alone and in combination with palbociclib;

  2. Effect of food on bioavailability of G1T48 [ Time Frame: Part 1, Cycle 1 Day -10 to Cycle 1 Day 1. ]
  3. 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. ]
  4. 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. ]
  5. 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. ]
  6. 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. ]
  7. Pharmacokinetics of palbociclib: Plasma - Trough concentration [ Time Frame: Part 3, Cycle 2 Day 1 to Cycle 3 Day 1. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Locations
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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
Belgium
Institut Jules Bordet
Brussels, Belgium, 1000
UZ Leuven
Leuven, Belgium, 3000
Georgia
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
Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081 HV
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ
Erasmus Medical Center
Rotterdam, Netherlands, 3015 GD
Sponsors and Collaborators
G1 Therapeutics, Inc.
Investigators
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Study Director: Clinical Contact G1 Therapeutics, Inc.
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Responsible Party: G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03455270    
Other Study ID Numbers: G1T48-01
2017-004502-17 ( EudraCT Number )
First Posted: March 6, 2018    Key Record Dates
Last Update Posted: February 26, 2020
Last Verified: February 2020

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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
Oral SERD
SERD
HER2-Negative
ER-Positive
ER+
HER2-
HER2 -ve
ER +ve
CDK 4/6 Inhibitor
Additional relevant MeSH terms:
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Breast Neoplasms
Carcinoma, Ductal
Carcinoma, Ductal, Breast
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Ductal, Lobular, and Medullary
Palbociclib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action