A study to investigate the safety, and effect of G1T38 on breast cancer when used in combination with Fulvestrant and to investigate level of G1T38 in the blood during treatment.
- Conditions
- Hormone Receptor-Positive, HER2 Negative Metastatic Breast Cancer after Endocrine FailureMedDRA version: 20.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001485-29-BG
- Lead Sponsor
- G1 Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 132
1. Women or men, 18 years or older
2. Histologically or cytologically confirmed diagnosis of breast cancer,
with evidence of metastatic or locally advanced disease, not amenable
to curative therapy (ie, surgical resection +/- radiation therapy)
3. Documented diagnosis of HR-positive tumor, ER-positive, and/or
progesterone receptor-positive, defined as = 1% positive stained cells,
utilizing an assay consistent with local standards
4. Documented HER2-negative tumor (immunohistochemistry [IHC]
score of 0 or 1+ or negative by in situ hybridization (fluorescence, dual,
chromogenic, or silver in situ hybridization) defined as HER2/CEP17
ratio < 2 or for single probe assessment, HER2 copy number < 45. Any menopausal status:
a. Postmenopausal women are defined as at least 60 years of age, have
undergone bilateral oophorectomy, medically confirmed ovarian failure
or are younger than 60 years of age and have had cessation of regular
menses for at least 12 consecutive months with no alternative
pathological or physiological cause and have serum levels of estradiol
and follicle stimulating hormone within the laboratory's reference range
for postmenopausal females
b. Pre- or perimenopausal women can be enrolled if amenable to be
treated with the LHRH agonist goserelin. Patients must have commenced
treatment with goserelin or an alternative LHRH agonist at least 28 days
prior to first dose of G1T38. If patients have received an alternative
LHRH agonist prior to study entry, they must switch to goserelin for the
duration of the trial.
6. Patients must satisfy one of the following criteria for prior therapy:
a. Progressed during treatment or within 12 months of completion of
adjuvant therapy with an aromatase inhibitor or tamoxifen
b. Progressed during treatment or within 2 months after the end of prior
aromatase inhibitor therapy for advanced/metastatic breast cancer, or
prior endocrine therapy for advanced/metastatic breast cancer if pre- or
perimenopausal
For advanced/metastatic disease
• Part 1: a maximum of 2 prior chemotherapy regimens is allowed in
addition to prior endocrine therapy
• Part 2: a maximum of 1 prior chemotherapy regimen is allowed in
addition to prior endocrine therapy
7. For Part 1 of the study, evaluable or measurable disease as defined by
RECIST, Version 1.1
8. For Part 2 of the study, approximately 75% of patients enrolled on
protocol Version 7.0 or later must have measurable disease as defined
by RECIST Version 1.1, including bone-only disease. Patients with
measurable bone-only metastatic cancer must have a lytic or mixed lyticblastic
lesion that can be accurately measured by CT or MRI per RECIST
Version
1.1. Up to approximately 25% of patients with bone-only
disease
that is non-measurable by RECIST Version 1.1 may be enrolled.
Tumor
lesions previously irradiated or subjected to other loco-regional
therapy
will only be deemed measurable if progression at the treated
site
after completion of therapy is clearly documented
9.
ECOG performance status 0 to 1
10.
Must meet all of the following laboratory parameters criteria:
a.
Hemoglobin = 90 g/L in absence of red cell transfusion within 14 days
of
first dose of G1T38
b.
Absolute neutrophil count = 1.5 × 109/L
c.
Platelet count = 100 × 109/L
d.
Estimated GFR of = 50 mL/min (by Cockcroft-Gault formula or 51Cr
EDTA)
e.
Total bilirubin = 1.5 × upper limit of normal (ULN); <3 x ULN if
documented
Gilbert's disease
f.
AST and ALT = 2.5 × ULN; = 5 × ULN in the presence of liver
met
A patient will not be eligible for participation in this study if any of the following criteria apply.
1. For Part 1 of the study, prior treatment with fulvestrant
2. For Part 2 of the study, prior treatment with any CDK inhibitor or fulvestrant
3. 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 are clinically stable off anticonvulsants and steroids for at least 28 days prior to first dose of G1T38.
4. Major surgery within 14 days of first screening visit
5. Receipt of chemotherapy within 21 days of first dose of G1T38
6. Receipt of any investigational medication within 28 days of first dose of G1T38
7. Concurrent radiotherapy to any site or radiotherapy within 14 days of first dose of G1T38 or previous radiotherapy to the target lesion sites (the sites that are to be followed for determination of a response) or prior radiotherapy to > 25% of bone marrow
8. Use of any of the following prohibited, orally administered cytochrome P450 CYP(3A) substrates with a narrow therapeutic index within 14 days of first dose of G1T38:
a. Astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, everolimus, pimozide, quinidine, sirolimus and tacrolimus
9. Patients taking bisphosphonates or denosumab for the treatment of osteoporosis or management of existing bone metastases must have been on a stable dose for at least 14 days prior to first dose of G1T38
10. Chronic use of systemic corticosteroids. Steroids given for physiological replacement (up to 10 mg prednisone or equivalent), as anti-emetics, by inhalation, and short course (up to 10 days) of oral/topical steroids given for allergic reactions or asthma flares are allowed.
11. Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure (Class III or IV as defined by the New York Heart Association [NYHA] functional classification system)
12. Known history of stroke, cerebrovascular accident, or myocardial infarction within 6 months prior to enrollment
13. Known serious active infection (eg, HIV, hepatitis B or C, tuberculosis, etc.). A negative screening test is not required for participation.
14. Psychiatric illness/social situations that would limit study compliance
15. Other uncontrolled serious chronic disease or conditions that in the investigator’s opinion could affect patient safety, compliance or follow-up in the protocol
16. Legal incapacity or limited legal capacity
17. Prior hematopoietic stem cell or bone marrow transplantation
18. QTc interval > 450 msec for males or > 470 msec for females using Fridericia method on screening ECG or known history of QTc prolongation
19. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of G1T38, such as history of GI surgery which may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or diarrhea of CTCAE Grade > 1
20. 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) prost
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method