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
- Conditions
- Advanced Breast CancerEstrogen Receptor-Positive HER2-Negative Advanced Breast Cancer10006291
- Registration Number
- NL-OMON50738
- Lead Sponsor
- G1 Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 45
For a patient to be eligible for participation in this study, all of the
following criteria must apply. A full list of inclusion criteria are provided
in Section 7.1.1 of the study protocol.
• Age 18 years or older females (postmenopausal only in Part 1 and any
menopausal status in Parts 2 and 3; pre- and peri-menopausal women in Parts 2
and 3 must be chemically or surgically postmenopausal)
• Histological or cytological confirmation of adenocarcinoma of the breast with
evidence of metastatic or locally advanced disease, which is not amenable to
surgical resection ± radiation therapy with curative intent
• Documented ER-positive tumor, defined as >= 1% positive stained cells
utilizing an assay consistent with local standards. The tumor may be
progesterone receptor positive or negative.
• Documented HER2-negative tumor per 2017 College of American Pathologists
(CAP) criteria
• Not eligible for standard therapy that would confer clinical benefit to the
patient
• For Parts 1 and 2 of the study, objective evidence of either progression
after an AI for metastatic/locally advanced disease OR recurrence while on or
within 12 months of the end of adjuvant treatment with an AI
• For Part 3, patients must meet at least ONE of the following:
- 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
• Not eligible for standard therapy that would confer clinical benefit to the
patient
• For Part 1 of the study, evaluable or measurable disease as defined by
RECIST, Version 1.1
• For Parts 2 and 3 of the study, approximately 75% of enrolled patients must
have measurable disease as defined by RECIST, Version 1.1
• Exposure to the following:
- Part 1: <= 3 lines of prior cytotoxic chemotherapy
- Part 2: <= 1 line of prior cytotoxic chemotherapy
- Part 1 and Part 2:
o <= 3 prior endocrine therapies in the metastatic setting
o Prior CDK4/6 inhibitor therapy and/or everolimus is allowed
- Part 3:
o <= 1 prior line of endocrine therapy in the metastatic setting
o <= 1 prior line of cytotoxic chemotherapy in the metastatic setting
o Prior CDK4/6 inhibitor therapy is not allowed
o Prior everolimus is allowed
• Required washout for FES PET (Parts 1 and 2 only), if applicable
- >= 5-week interval since the last use of tamoxifen (or other selective
estrogen receptor modulators [SERMs]) or fulvestrant (or other SERDs)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy > 12 weeks
• Adequate bone marrow reserve and organ function as demonstrated by the
following laboratory values:
- Hemoglobin >= 9 g/dL
- Absolute neutrophil count (ANC) >= 1.5 × 109/L
- Platelet count >= 100 × 109/L
- Estimated glomerular filtration rate >= 50 mL/minute/1.73 m2
- Total bilirubin <= 1.5 × ULN
- ALT and AST <= 3 × ULN; <= 5 × ULN in the presence of liver metastases
A patient will not be eligible for participation in this study if any of the
following criteria apply. A full list of exclusion criteria are provided in
Section 7.1.2 of the study Protocol.
• Patients with immediately life-threatening or rapidly progressive disease or
those who experience rapid visceral recurrence during adjuvant endocrine therapy
• Known active uncontrolled or symptomatic central nervous system (CNS)
metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by
clinical symptoms, cerebral edema, and or progressive growth. Patients with a
history of CNS metastases or cord compression are eligible if they have been
definitively treated (eg, radiotherapy, stereotactic surgery) and clinically
stable (including patients with residual CNS symptoms/deficits) off
enzyme-inducing anticonvulsants and steroids for at least 28 days prior to the
first dose of study drug (patients may continue to receive non-enzyme-inducing
anticonvulsants throughout the study if needed)
• Major surgery, chemotherapy, radiotherapy, or other anticancer therapy within
14 days of first dose of study drug
• Prior hematopoietic stem cell or bone marrow transplantation
• Blood transfusions or hematopoietic growth factor therapy within 14 days
prior to the first dose of study drug
• Concurrent use of prohibited medications
• Any unresolved toxicities from prior surgeries or therapies > Grade 1 (Common
Terminology Criteria for Adverse Events [CTCAE] Version 5.0) at the time of
starting study drug with the exception of alopecia (any grade) and Grade 2
peripheral neuropathy
• Cardiac criteria as outlined in Section 7.1.2 of the study protocol
• Known clinically significant history of liver disease (excluding metastases
to the liver)
• Unexplained symptomatic endometrial disorders
• Any evidence of severe or uncontrolled systemic diseases, which in the
investigator opinion makes it undesirable for the patient to participate in the
study or that would jeopardize compliance with the protocol
• Known chronic, active infection
• Refractory nausea and vomiting, chronic gastrointestinal (GI) disease, GI
ulcer, GI bleeding, inability to swallow the formulated product, or previous
significant bowel resection that would preclude adequate absorption of study
drug
• History of other malignancies, except for the following: (1) adequately
treated basal or squamous cell carcinoma of the skin; (2) curatively treated a)
in situ carcinoma of the uterine cervix, b) superficial bladder cancer; or (3)
other curatively treated solid tumor with no evidence of disease for >= 3 years
• For Part 3 of the study, prior CDK4/6 inhibitor therapy, oral SERDs, or
selective estrogen receptor covalent antagonists (SERCAs) in any setting
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary:<br /><br>1) AEs, SAEs, and other safety measures (ECGs, physical examinations, vital<br /><br>signs, and laboratory parameters)<br /><br>2) Safety, tolerability and DLTs</p><br>
- Secondary Outcome Measures
Name Time Method