Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Patients With Previously Treated Extensive Stage SCLC Receiving Topotecan Chemotherapy

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ClinicalTrials.gov Identifier: NCT02514447

Recruitment Status : Active, not recruiting

First Posted : August 3, 2015

Last Update Posted : May 25, 2018

Sponsor:

Information provided by (Responsible Party):

G1 Therapeutics, Inc.

Study Description

Brief Summary:

This is a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to topotecan in patients previously treated for extensive-stage SCLC.

The study consists of 2 parts: a limited open-label, dose-finding portion (Part 1), and a randomized double-blind portion (Part 2). Both parts include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit. The open-label portion enrolled 32 patients and the randomized portion will enroll approximately 90 patients.

Condition or disease	Intervention/treatment	Phase
Small Cell Lung Cancer	Drug: Trilaciclib Drug: Placebos Drug: Topotecan	Phase 1 Phase 2

Study Design


Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	120 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official 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
Actual Study Start Date :	October 5, 2015
Estimated Primary Completion Date :	April 2019
Estimated Study Completion Date :	August 2019

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Lung cancer

Drug Information available for: Topotecan hydrochloride Topotecan

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Trilaciclib (G1T28) + Topotecan All patients in Part 1 will receive trilaciclib (G1T28) prior to standard chemotherapy, topotecan. Patients will have PK assessment completed on days 1 and 4 in cycle 1 only. All patents will be monitored for safety and tumor response based on RECIST version 1.1. Safety surveillance reporting of AEs and concomitant medications commences at the time that informed consent is obtained and continues through the Post Treatment Visit.	Drug: Trilaciclib Other Names: G1T28 CDK 4/6 inhibitor Drug: Topotecan
Experimental: Trilaciclib (G1T28)/Placebo + Topotecan All patients in Part 2 will be randomized 2:1 to receive either trilaciclib (G1T28) or placebo administered prior to standard chemotherapy, topotecan. Patients will have limited PK assessments completed on day 4 in cycle 1 only. All patents will be monitored for safety and tumor response based on RECIST version 1.1. Safety surveillance reporting of AEs and concomitant medications commences at the time that informed consent is obtained and continues through the Post Treatment Visit.	Drug: Trilaciclib Other Names: G1T28 CDK 4/6 inhibitor Drug: Placebos Drug: Topotecan

Arm

Intervention/treatment

Experimental: Trilaciclib (G1T28) + Topotecan

All patients in Part 1 will receive trilaciclib (G1T28) prior to standard chemotherapy, topotecan. Patients will have PK assessment completed on days 1 and 4 in cycle 1 only. All patents will be monitored for safety and tumor response based on RECIST version 1.1. Safety surveillance reporting of AEs and concomitant medications commences at the time that informed consent is obtained and continues through the Post Treatment Visit.

Drug: Trilaciclib

Other Names:

G1T28
CDK 4/6 inhibitor

Drug: Topotecan

Experimental: Trilaciclib (G1T28)/Placebo + Topotecan

All patients in Part 2 will be randomized 2:1 to receive either trilaciclib (G1T28) or placebo administered prior to standard chemotherapy, topotecan. Patients will have limited PK assessments completed on day 4 in cycle 1 only. All patents will be monitored for safety and tumor response based on RECIST version 1.1. Safety surveillance reporting of AEs and concomitant medications commences at the time that informed consent is obtained and continues through the Post Treatment Visit.

Drug: Trilaciclib

Other Names:

G1T28
CDK 4/6 inhibitor

Drug: Placebos
Drug: Topotecan

Outcome Measures

Primary Outcome Measures :

Dose Limiting Toxicity [ Time Frame: Days 1-21 of Cycle 1 ]
Treatment related adverse events (AE) [ Time Frame: Up to 24 weeks ]

Secondary Outcome Measures :

Pharmacokinetic profile for Trilaciclib (G1T28) and Topotecan [ Time Frame: Days 1 and 4 of Cycle 1 ]
Blood samples for the determination of trilaciclib (G1T28) and topotecan
Progression free survival (PFS) [ Time Frame: 24 Months ]
Overall survival (OS) [ Time Frame: 24 Month ]
Hematologic parameters [ Time Frame: Up to 20 weeks ]
The following will be assessed: hemoglobin, hematocrit, white blood cells with differential and platelet counts
Tumor response based on RECIST, Version 1.1 [ Time Frame: Up to 20 weeks ]
Need for RBC and platelet transfusions [ Time Frame: Up to 20 weeks ]
Need for treatment with hematopoietic growth factors [ Time Frame: Day 22 ]
Incidence of chemotherapy dose reductions and dose interruptions overall [ Time Frame: Up to 20 weeks ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female subjects aged ≥18 years
Unequivocally confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
Progression during or after prior first- or second-line chemotherapy and eligible to receive topotecan therapy
At least 1 target lesion that is measurable by RECIST, Version 1.1
Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
Adequate organ function

Exclusion Criteria:

Presence of symptomatic brain metastases requiring immediate treatment with radiation therapy or steroids.
Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure
Known history of stroke or cerebrovascular accident within 6 months prior to enrollment
Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could affect compliance or follow-up in the protocol
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)
Receipt of any investigational medication within 2 weeks prior to enrollment
History of topotecan treatment for SCLC

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02514447

Show 50 Study Locations

Sponsors and Collaborators

G1 Therapeutics, Inc.

Investigators


Study Director:	Clinical Contact	G1 Therapeutics, Inc.

More Information


Responsible Party:	G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT02514447 History of Changes
Other Study ID Numbers:	G1T28-03 2016-004611-13 ( EudraCT Number )
First Posted:	August 3, 2015 Key Record Dates
Last Update Posted:	May 25, 2018
Last Verified:	May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No


Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by G1 Therapeutics, Inc.:


SCLC

Additional relevant MeSH terms:


Lung Neoplasms Small Cell Lung Carcinoma Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases	Carcinoma, Bronchogenic Bronchial Neoplasms Topotecan Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents

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