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

• Register: EUCTR
• Last refreshed on: 14 April 2020
• Main ID: EUCTR2016-004466-26-BE
• Date of registration: 06/06/2017
• Prospective Registration: Yes
• Primary sponsor: G1 Therapeutics
• Public title: 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
• Scientific title: Phase 2 Study of the Safety, Efficacy, and Pharmacokinetics of G1T28 in Patients with Metastatic Triple Negative Breast Cancer Receiving Gemcitabine and Carboplatin Chemotherapy
• Date of first enrolment: 10/07/2017
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004466-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Group 1 will not receive any additional drug with GC and Group 2 and 3 will receive G1T28 with GC; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Bulgaria, Croatia, Macedonia, the former Yugoslav Republic of, Serbia, Slovenia, United States

Contacts

• Name: Clinical Trial Info
• Affiliation: G1 Therapeutics, Inc

• Name: Clinical Trial Info
• Affiliation: G1 Therapeutics, Inc

Key inclusion & exclusion criteria

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 Stage IV metastatic or locally recurrent 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 IHC (0 or 1+) or negative, nonamplified, by fluorescent in situ hybridization (ratio < 2.0) per local assessment
4. Patients must have tumor tissue available from their TNBC diagnostic sample (archived tissue allowed) for retrospective analysis of potential biomarkers
5. At least 1 target lesion that is measurable by RECIST, Version 1.1 (Eisenhauer et al. 2009)
6. Hemoglobin = 9.0 g/dL in absence of RBC transfusion within 14 days prior to first dose of trilaciclib
7. ANC = 1.5 × 109/L
8. Platelet count = 100 × 109/L
9. Serum creatinine = 1.5 mg/dL or creatinine clearance = 60 mL/minute
10. Total bilirubin = 1.5 × upper limit of normal (ULN); < 3 × ULN if the patient has documented Gilbert’s disease
11. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 × ULN; = 5 × ULN in the presence of liver metastases
12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
13. Resolution of nonhematologic toxicities from prior therapy or surgical procedures to = Grade 1 (except alopecia)
14. Predicted life expectancy of = 3 months
15. Contraception:
a. For females: All females of childbearing potential must have a negative serum beta human chorionic gonadotropin (ß hCG) test result at screening. 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 in line with
Exclusion criteria:
1. More than 1 prior chemotherapy regimen for locally recurrent or metastatic TNBC (non-cytotoxic therapies are not considered prior chemotherapy)
2. Patients with prior treatment of locally recurrent or metastatic breast cancer with gemcitabine, carboplatin, or cisplatin. (Previous adjuvant/neoadjuvant chemotherapy with carboplatin, cisplatin, or gemcitabine is allowed if = 12 months have elapsed between the date of last adjuvant/neoadjuvant chemotherapy administration and first documented local or distant disease recurrence)
3. Less than 12 months between the date of last adjuvant/neoadjuvant chemotherapy administration (with curative intent) and first documented local or distant disease recurrence
4. 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
5. 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 for at least 28 days prior to the first dose and have been off corticosteroids for at least 4 weeks. Steroids for physiological replacement, as antiemetics, by inhalation, and short course of oral/topical steroids given for allergic reactions or asthma flares are allowed
6. 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)
7. Known history of stroke or cerebrovascular accident within 6 months prior to first dose of trilaciclib
8. Known serious active infection (eg, human immunodeficiency virus [HIV], hepatitis B or C, tuberculosis, etc.)
9. 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
10. Prior hematopoietic stem cell or bone marrow transplantation
11. Concurrent radiotherapy to any site or radiotherapy within 2 weeks prior to the first dose of trilaciclib
12. Receipt of any investigational medication within 30 days prior to the first dose of trilaciclib
13. Receipt of any cytotoxic chemotherapy within 3 weeks prior to the first dose of trilaciclib
14. Hypersensitivity to cisplatin or other platinum-containing compounds, or mannitol
15. Pregnant or lactating women



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Locally recurrent or metastatic Triple Negative Breast Cancer
MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Trilaciclib
Product Code: G1T28
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: G1T28 x 2HCl
Current Sponsor code: G1T28
Other descriptive name: G1T28
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Main Objective: Assess the safety and tolerability of trilaciclib administered with GC (gemcitabine and carboplatin) therapy

Timepoint(s) of evaluation of this end point: As defined per protocol.

Primary end point(s): Safety and Tolerability of Trilaciclib with GC therapy

Secondary Objective: Assess tumor response and duration of response based on RECIST, Version 1.1
Assess PFS and OS
Assess dose intensity of gemcitabine and carboplatin
Assess the PK profile of trilaciclib
Assess the PK profile of gemcitabine and carboplatin when administered with and without trilaciclib
Assess the hematologic profile (kinetics and incidence/duration/frequency of toxicities) of trilaciclib administered with GC therapy
Assess the incidence of febrile neutropenia
Assess the incidence of infections
Assess the utilization of RBC and platelet transfusions
Assess the utilization of hematopoietic growth factors
Assess the utilization of systemic antibiotics
Assess the incidence of chemotherapy dose reductions and dose interruptions overall
Assess the incidence of Grade 2 or greater nephrotoxicity
Determine the dose schedule of trilaciclib administered with GC therapy

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: As defined per protocol.

Secondary end point(s): Assess tumor response and duration of response based on RECIST, Version 1.1
Assess PFS and OS
Assess dose intensity of gemcitabine and carboplatin
Assess the PK profile of trilaciclib
Assess the PK profile of gemcitabine and carboplatin when administered with and without trilaciclib
Assess the hematologic profile (kinetics and incidence/duration/frequency of toxicities) of trilaciclib administered with GC therapy
Assess the incidence of febrile neutropenia
Assess the incidence of infections
Assess the utilization of RBC and platelet transfusions
Assess the utilization of hematopoietic growth factors
Assess the utilization of systemic antibiotics
Assess the incidence of chemotherapy dose reductions and dose interruptions overall
Assess the incidence of Grade 2 or greater nephrotoxicity
Determine the dose schedule of trilaciclib administered with GC therapy

Secondary ID(s)

G1T28-04

NCT02978716

Source(s) of Monetary Support

G1 Therapeutics, Inc

Ethics review

Status: Approved
Approval date: 10/07/2017
Contact: