A clinical trial to test the safety, efficacy and plasma concentration of G1T28 in patients with metastatic triple negative breast cancer receiving gemcitabine and carboplatin chemotherapy

Phase 1

Conditions: ocally recurrent or metastatic Triple Negative Breast Cancer
MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-004466-26-HR

Lead Sponsor: G1 Therapeutics

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 142

Inclusion Criteria

For a patient to be eligible for participation in this study, all of the following criteria must apply.
1. Female or male patients with evaluable locally recurrent or Stage IV metastatic TNBC
2. Age = 18 years
3. Histologically or cytologically confirmed hormone (estrogen and progesterone) receptor negative tumor on local pathology IHC assessment (defined as < 10% nuclei staining) and human epidermal growth factor receptor 2 (HER2)-negative, nonoverexpressing (by local assessment of IHC [0 or 1+] OR fluorescent in situ hybridization [ratio < 2.0] OR average HER2 gene copy number of < 4 signals/nucleus)
4. Patients must have tumor tissue available from their TNBC diagnostic sample (archived tissue allowed) for retrospective analysis of potential biomarkers
5. Hemoglobin = 9.0 g/dL in absence of RBC transfusion within 14 days prior to first dose of trilaciclib
6. ANC = 1.5 × 109/L
7. Platelet count = 100 × 109/L
8. Serum creatinine = 1.5 mg/dL or creatinine clearance = 60 mL/minute
9. Total bilirubin = 1.5 × upper limit of normal (ULN); < 3 × ULN if the patient has documented Gilbert's disease
10. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 × ULN; = 5 × ULN in the presence of liver metastases
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
12. Resolution of nonhematologic toxicities from prior therapy or surgical procedures to = Grade 1 (except alopecia)
13. Predicted life expectancy of = 3 months
14. Contraception:
a. For females: All females of childbearing potential must have a negative serum beta human chorionic gonadotropin (ß hCG) test result at screening and a negative serum or urine pregnancy test result at baseline (within 24 hours of the first dose). Females must be either postmenopausal, surgically sterile, or agree to use 2 forms of highly effective contraception during the study and for 6 months following discontinuation of study treatment
i. Postmenopausal is defined as at least 60 years of age, medically confirmed ovarian failure, 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/or serum levels of estradiol and follicle stimulating hormone within the laboratory's reference range for postmenopausal females
ii. Acceptable surgical sterilization techniques are complete or partial hysterectomy or bilateral tubal ligation with surgery at least 6 months prior to dosing, and bilateral oophorectomy with surgery at least 2 months prior to dosing
iii. Highly effective methods of contraception are those that result in a low failure rate (ie, less than 1% per year) when used consistently and correctly. These include the following:
1. Established use of oral, injected or implanted hormonal methods of contraception (stable dose at least 3 months prior to dosing)
2. Placement of an intrauterine device or intrauterine system
3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/suppository. Barrier methods alone (without spermicide) are not acceptable methods. Likewise, spermicide alone is not an acceptable method
4. Male sterilization (with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
5. True abstinence, when this is

Exclusion Criteria

A patient will not be eligible for participation in this study if any of the following criteria apply.
1. More than 2 prior chemotherapy regimens for locally recurrent or metastatic TNBC (noncytotoxic therapies are not considered prior lines of therapy). For a regimen to be a line of therapy, the patient must have disease progression after that therapy prior to the start date of the next therapy or enrollment in this study. Therapy given in the neoadjuvant/adjuvant setting where the patient has recurrent disease > 12 months after the last dose of therapy will NOT be considered a line of therapy in the locally recurrent or metastatic setting.
2. Malignancies other than TNBC within 3 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
3. Presence of CNS metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids (ie, patient must be off steroids administered for brain metastases for at least 14 days prior to the first dose of G1T28).
4. 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)
5. Known history of stroke or cerebrovascular accident within 6 months prior to first dose of trilaciclib
6. Known serious active infection (eg, human immunodeficiency virus [HIV], hepatitis B or C, tuberculosis, etc.)
7. Other uncontrolled serious chronic disease or psychiatric condition that in the investigator's opinion could affect patient safety, compliance, or follow-up in the protocol
8. Prior hematopoietic stem cell or bone marrow transplantation
9. Concurrent radiotherapy to any site or radiotherapy within 2 weeks prior to the first dose of trilaciclib
10. Receipt of any investigational medication within 30 days prior to the first dose of trilaciclib
11. Receipt of any cytotoxic chemotherapy within 3 weeks prior to the first dose of trilaciclib
12. Receipt of any low-dose systemic chemotherapeutic agent given for a nononcologic purpose within 3 weeks prior to enrollment (eg, low-dose methotrexate for rheumatoid arthritis)
13. Hypersensitivity to cisplatin or other platinum-containing compounds, or mannitol
14. Pregnant or lactating women

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

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