Clinical Trials Register

Summary
EudraCT Number:	2016-004611-13
Sponsor's Protocol Code Number:	G1T28-03
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-02-16
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2016-004611-13

A.3

Full title of the trial

Phase 1b/2a Safety and Pharmacokinetic Study of G1T28 in Patients with Previously Treated Extensive-Stage Small Cell Lung Cancer (SCLC) Receiving Topotecan Chemotherapy

Fase 1b/2a studie naar de veiligheid en farmacokinetiek van G1T28 bij patiënten met eerder behandelde kleincellige longkanker (SCLC) in het uitgebreide stadium, die chemotherapie met topotecan krijgen

Étude de phase 1b/2a évaluant la sécurité d’emploi et la pharmacocinétique du G1T28 chez les patients atteints d’un cancer du poumon à petites cellules (CPPC) de stade étendu traité antérieurement et qui reçoivent une chimiothérapie à base de topotécan

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

G1T28-03

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	G1 Therapeutics
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	G1 Therapeutics, Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	G1 Therapeutics, Inc
B.5.2	Functional name of contact point	Clinical Trial Info
B.5.3	Address:
B.5.3.1	Street Address	PO Box 110341
B.5.3.2	Town/ city	Research Triangle Park
B.5.3.3	Post code	NC 27709
B.5.3.4	Country	United States
B.5.4	Telephone number	+19192139835
B.5.5	Fax number	+19197415830
B.5.6	E-mail	clinicalinfo@g1therapeutics.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Trilaciclib
D.3.2	Product code	G1T28
D.3.4	Pharmaceutical form	Powder for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	G1T28 Di-HCl
D.3.9.2	Current sponsor code	G1T28
D.3.9.3	Other descriptive name	G1T28
D.3.9.4	EV Substance Code	SUB181989
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	240
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Extensive-Stage Small Cell Lung Cancer

E.1.1.1

Medical condition in easily understood language

Cancer of small lung cells

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	20.0
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)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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 Parts 2A and 2B- Phase 2a study)
2. Assess the safety and tolerability of G1T28 administered with topotecan

E.2.2

Secondary objectives of the trial

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

E.2.3

Trial contains a sub-study

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. Progression during or after prior first- or second-line chemotherapy and eligible to receive topotecan therapy (immunotherapy treatment alone, ie, not administered with chemotherapy, should not be counted as a line of chemotherapy)
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 (β-hCG) test result at screening and negative serum or urine β-hCG test result at baseline.
Females must be either postmenopausal, surgically sterile, or using an acceptable method of contraception in combination with a barrier method.
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 to be used in combination with a barrier method are an intrauterine device, contraceptive implant, oral contraceptive (stable dose of the same hormonal contraceptive product for at least 3 months prior to dosing), or a vasectomized partner. These methods are to be utilized 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

E.4

Principal 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. Receipt of any low-dose systemic chemotherapeutic agent given for a nononcologic purpose within 4 weeks prior to enrollment (eg, low-dose methotrexate for rheumatoid arthritis)
14. Hypersensitivity to any of the components of the formulation of topotecan
15. Legal incapacity or limited legal capacity
16. Pregnant or lactating women

E.5 End points

E.5.1

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 Parts 2A and 2B - Phase 2a study)

E.5.1.1

Timepoint(s) of evaluation of this end point

As defined per protocol.

E.5.2

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 Parts 2A and 2B - Phase 2a study)

E.5.2.1

Timepoint(s) of evaluation of this end point

As defined per protocol.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Bosnia and Herzegovina

Macedonia, the former Yugoslav Republic of

Serbia

United States

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

Patients will be followed for survival via monthly phone calls at a minimum until 50% of the patients in Parts 2A and 2B of the study have died.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Information not present in EudraCT

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

For those patients in the survival follow-up who have not progressed at the time of study drug discontinuation, tumor assessments, including all sites of disease, will be assessed radiologically by CT or MRI every 2 months (approximately 60 ± 7 days) until the occurrence of progressive disease or study completion.
Patients will continue to receive standard of care treatment as per institutional guidelines.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-03-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-10-04

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