A study to assess the safety and tolerability of combining G1T28 with etoposide and carboplatin therapy and to evaluate the effect of G1T28 on blood cell production affected by chemotherapy.

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2016-001583-11-HU
• Date of registration: 28/07/2016
• Prospective Registration: Yes
• Primary sponsor: G1 Therapeutics
• Public title: A study to assess the safety and tolerability of combining G1T28 with etoposide and carboplatin therapy and to evaluate the effect of G1T28 on blood cell production affected by chemotherapy.
• Scientific title: Phase 1b/2a Safety and Pharmacokinetic Study of G1T28 in Patients with Extensive-Stage Small Cell Lung Cancer (SCLC) Receiving Etoposide and Carboplatin Chemotherapy - G1T28 safety and pharmacokinetic study in patients receiving etoposide and carboplatin
• Date of first enrolment: 26/09/2016
• Target sample size: 110
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001583-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Part 1 of the study is open label. Part 2 is a randomised, double-blind, placebo-controlled design; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Georgia, Hungary, Moldova, Republic of, Poland, Romania, Spain, United Kingdom, United States

Contacts

• Name: Clinical Information Contact
• Affiliation: G1 Therapeutics

• Name: Clinical Information Contact
• Affiliation: G1 Therapeutics

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age = 18 years
2. Unequivocally confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
3. Extensive-stage disease
4. At least 1 target lesion that is unirradiated and measurable by RECIST, Version 1.1 (Eisenhauer 2009)
5. Hemoglobin = 9.0 g/dL
6. Absolute neutrophil count = 1.5 × 109/L
7. Platelet count = 100 × 109/L
8. Creatinine = 1.5 mg/dL OR glomerular filtration rate (GFR) of = 60 mL/min (by Cockcroft-Gault formula [Cockcroft and Gault 1976]); creatinine clearance calculated from an isotopic method or a 24-hour urine collection may be used instead of an estimated GFR by the Cockcroft-Gault formula
9. Total bilirubin = 1.5 × upper limit of normal (ULN)
10. AST and ALT = 2.5 × ULN; = 5 × ULN in the presence of liver metastases
11. Serum albumin = 3 g/dL
12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
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 at baseline. Females must be either postmenopausal, surgically sterile, or using an acceptable method of contraception. Acceptable surgical sterilization techniques are hysterectomy, bilateral tubal ligation with surgery at least 6 months prior to dosing, and bilateral oophorectomy, with surgery at least 2 months prior to dosing. Acceptable methods of contraception are an intrauterine device, contraceptive implant, oral contraceptive (stable dose of the same hormonal contraceptive product for at least 3 months prior to dosing), a vasectomized partner, and a barrier method (condom or diaphragm) during the study and for 3 months after discontinuation of treatment
b. For males: Patients with female partner of childbearing potential must agree to use a highly effective form of birth control, which entails the use of oral, injected, or implanted hormonal methods of contraception or an intrauterine device/system by the female partner, in combination with a barrier method (eg, condom, diaphragm, cervical cap) during the study and for 3 months after discontinuation of treatment, and will also refrain from sperm donation for 3 months following completion of the study
15. Able to understand and sign an informed consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion criteria:
1. Prior chemotherapy for limited or extensive-stage SCLC
2. Presence of symptomatic brain metastases requiring immediate treatment with radiation therapy or steroids.
3. 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) prostate cancer, or c) superficial bladder cancer; or (3) other curatively treated solid tumor with no evidence of disease for = 3 years
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 enrollment
6. Serious active infection
7. Psychiatric illness/social situations that would limit study compliance
8. Other uncontrolled serious chronic disease or conditions that in the investigator’s opinion could affect compliance or follow-up in the protocol
9. Known human immunodeficiency virus (HIV), known hepatitis B virus (HBV), or known hepatitis C virus (HCV) positive that is symptomatic or requiring active therapy
10. Concurrent radiotherapy to any site or radiotherapy within 2 weeks prior to enrollment or previous radiotherapy to the target lesion sites (the sites that are to be followed for determination of a response)
11. Receipt of any investigational medication within 4 weeks prior to enrollment
12. Hypersensitivity to any of the components of the formulation of etoposide or etoposide phosphate
13. Hypersensitivity to cisplatin or other platinum-containing compounds, or mannitol
14. Legal incapacity or limited legal capacity
15. Pregnant or lactating women





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

Health Condition(s) or Problem(s) studied

Extensive-Stage Small Cell Lung Cancer (SCLC)
MedDRA version: 19.0 Level: PT Classification code 10041068 Term: Small cell lung cancer extensive stage System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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

Intervention(s)

Product Name: G1T28 Di-HCl
Product Code: G1T28
Pharmaceutical Form: Solution for infusion
Current Sponsor code: G1T28
Other descriptive name: G1T28 Di-HCl
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: As defined in the protocol

Main Objective: Assess the DLTs and define the Phase 2 dose of G1T28 administered with E/P therapy.
Assess the safety and tolerability of G1T28 administered with E/P therapy.

Secondary Objective: Assess the PK profile of G1T28, Assess the PK profile of etoposide and carboplatin when administered with G1T28, Assess the hematologic profile (kinetics and incidence/duration/frequency of toxicities) of G1T28 administered with E/P 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, Assess tumor response based on RECIST, Version 1.1, Assess PFS and overall survival

Primary end point(s): Efficacy evaluation will be based on the following endpoints: hematologic kinetics, hematologic toxicities, chemotherapy exposure and compliance, other efficacy endpoints and exploratory efficacy.
Safety will be assessed by evaluation of AEs, infusion-related reactions, vital signs, physical examination, ECG readings, clinical hematology, chemistry and urinalysis results, concomitant medications, tumour response and best overall response based on RECIST, Version 1.1, progression-free survival and overall survival.
Exploratory analyses examining the relationship between hematologic toxicity rates and hematologic changes with study drug exposure will be performed based on rate of chemotherapy interruptions and rate of chemotherapy reductions.
Exploratory analyses will be performed to assess the impact of hematologic kinetics on overall survival, PFS, and best overall response rate. Similarly, exploratory analyses will be performed to assess the impact of cumulative chemotherapy exposure on overall survival, PFS, and best overall response rate. Exploratory analyses will be described in the SAP.
The relationship between G1T28 plasma concentration and hematologic parameter values will be assessed with the Pearson product-moment correlation statistics.
During Part 1 of the study, serial blood samples will be collected on Days 1 and 3 of Cycle 1 to determine G1T28, etoposide, and carboplatin plasma concentrations.
To evaluate the impact of G1T28 administration on chemotherapy-induced changes of the immune system, peripheral blood immune subsets will be characterized in patients enrolled into Part 2 of the study. The immunophenotypic change from baseline will be listed and summarized by treatment arm, if data warrant.
Additional exploratory analyses on the relationship between the immunophenotypic changes and safety and efficacy findings may be performed.

Secondary ID(s)

G1T28-02

Source(s) of Monetary Support

G1 Therapeutics

Ethics review

Status: Approved
Approval date:
Contact: