E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Extensive-Stage Small Cell Lung Cancer (SCLC) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041068 |
E.1.2 | Term | Small cell lung cancer extensive stage |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (β-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.
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
As defined in the protocol |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Dose-finding study to assess the safety, dose-limiting toxicities and pharmacokinetics of G1T28 |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Part 1 of the study is open label. Part 2 is a randomised, double-blind, placebo-controlled design |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Czech Republic |
France |
Georgia |
Hungary |
Moldova, Republic of |
Poland |
Romania |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Survival follow up will continue until a minimum of 50% patients in Part 2 have died. Final analysis will be completed when last patient completed Post Treatment Visit (PTV). If survival follow up continues past last patient PTV then end of study analysis will be completed as a supplementary analysis. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |