A clinical trial to test the safety and plasma concentration of G1T28 in combination with topotecan in patients with previously treated extensive stage small cell lung cancer

• Register: EUCTR
• Last refreshed on: 4 January 2022
• Main ID: EUCTR2016-004611-13-SI
• Date of registration: 08/03/2017
• Prospective Registration: Yes
• Primary sponsor: G1 Therapeutics
• Public title: A clinical trial to test the safety and plasma concentration of G1T28 in combination with topotecan in patients with previously treated extensive stage small cell lung cancer
• Scientific title: Phase 1b/2a Safety and Pharmacokinetic Study of G1T28 in Patients with Previously Treated Extensive-Stage Small Cell Lung Cancer (SCLC) Receiving Topotecan Chemotherapy
• Date of first enrolment: 22/05/2017
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004611-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; 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): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Bosnia and Herzegovina, 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:
1. Age = 18 years
2. Unequivocally confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
3. Progression during or after prior first- or second-line chemotherapy and eligible to receive topotecan therapy
4. At least 1 target lesion that is measurable by RECIST, Version 1.1
5. Absolute neutrophil count = 1.5 × 109/L
6. Platelet count = 100 × 109/L
7. Creatinine = 1.5 mg/dL and creatinine clearance (CrCl) of = 60 mL/minute)
8. Total bilirubin = 1.5 × upper limit of normal (ULN)
9. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 × ULN; = 5 × ULN in the
presence of liver metastases
10. Serum albumin = 3 g/dL
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
12. All clinically significant toxicities from previous anticancer therapy must have resolved to = Grade 1 (except for hemoglobin)
13. 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 negative serum or urine ß-hCG test result 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
14. 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 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion criteria:
1. History of topotecan treatment for SCLC
2. Presence of 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. History of upper gastrointestinal bleeding, ulceration, perforation, or significant gastrointestinal disease within 12 months prior to study enrollment
10. Known human immunodeficiency virus (HIV) positive; known hepatitis B virus (HBV) positive; or known hepatitis C virus (HCV) positive that is symptomatic or requiring active therapy
11. 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)
12. Receipt of any systemic chemotherapy regimen within 4 weeks prior to enrollment or a noncytotoxic investigational medication within 2 weeks prior to enrollment
13. Hypersensitivity to any of the components of the formulation of topotecan
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

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

Extensive-Stage Small Cell Lung Cancer
MedDRA version: 19.1 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)

Intervention(s)

Product Name: Trilaciclib
Product Code: G1T28
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: G1T28 Di-HCl
Current Sponsor code: G1T28
Other descriptive name: G1T28
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 240-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: 1. Assess the dose -limiting toxicities (DLTs) and define the Phase 2 dose of G1T28 administered with topotecan (please note this is related only to Part 1 - Phase 1b study; we will be conducting only Part 2- Phase 2a study)
2. Assess the safety and tolerability of G1T28 administered with topotecan

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

Secondary Objective: 1. Assess the pharmacokinetic (PK) profile of G1T28
2. Assess the PK profile of topotecan when administered with G1T28
3. Assess the hematologic profile (kinetics and incidence/duration/frequency of toxicities) of G1T28 administered with topotecan
4. Assess the incidence of febrile neutropenia
5. Assess the incidence of infections
6. Assess the utilization of red blood cells (RBC) and platelet transfusions
7. Assess the utilization of hematopoietic growth factors
8. Assess the utilization of systemic antibiotics
9. Assess the incidence of chemotherapy dose reductions and dose interruptions overall
10. Assess the incidence of Grade 2 or greater nephrotoxicity
11. Assess tumor response based on RECIST, Version 1.1
12. Assess progression free survival (PFS) and overall survival

Primary end point(s): To assess the safety and tolerability of combining G1T28 with topotecan and to evaluate the effect of G1T28) on chemotherapy induced myelosuppression.

(NOTE: relevant for Part 2 - Phase 2a study)

Secondary Outcome(s)

Secondary end point(s): • To assess the pharmacokinetic (PK) profile of G1T28
• To assess the hematologic profile (kinetics and incidence/duration/frequency of toxicities) of G1T28 administered with topotecan
• To assess the incidence of febrile neutropenia
• To assess the incidence of infections
• To assess the utilization of Red Blood Cells (RBC) and platelet transfusions
• To assess the utilization of hematopoietic growth factors
• To assess the utilization of systemic antibiotics
• To assess the incidence of chemotherapy dose reductions and dose interruptions overall
• To assess the incidence of Grade 2 or greater nephrotoxicity
• To assess tumor response based on RECIST,Version 1.1
• To assess progession-free survival (PFS) and overall survival

(NOTE: relevant for Part 2 - Phase 2a study)

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

Secondary ID(s)

2016-004611-13-BE

G1T28-03

Source(s) of Monetary Support

G1 Therapeutics, Inc

Ethics review

Status: Approved
Approval date: 18/05/2017
Contact: