Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Etoposide and Carboplatin in Extensive Stage Small Cell Lung Cancer (SCLC)

NCT ID: NCT02499770

Last Updated: 2020-08-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

122 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-06-26

Study Completion Date

2019-02-22

Brief Summary

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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 carboplatin and etoposide in first line treatment for patients with newly diagnosed 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. Approximately, 90 patients will be enrolled in the study; 20 patients in the Part 1 and 70 patients in the Part 2 portion.

Detailed Description

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Conditions

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Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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trilaciclib + carboplatin/etoposide

All patients in part 1 will receive trilaciclib (G1T28) prior to standard chemotherapy- carboplatin and etoposide. Patients will have PK assessments completed on days 1 and 3 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.

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

Trilaciclib

Intervention Type DRUG

Etoposide

Intervention Type DRUG

trilaciclib/placebo + carboplatin/etoposide

All patients enrolled in part 2 will be randomized to receive either trilaciclib (G1T28) or placebo administered prior to standard chemotherapy- carboplatin and etoposide. 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.

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

Placebo

Intervention Type DRUG

Trilaciclib

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Interventions

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Carboplatin

Intervention Type DRUG

Placebo

Intervention Type DRUG

Trilaciclib

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Other Intervention Names

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Paraplatin G1T28 VP-16 Toposar

Eligibility Criteria

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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
* At least 1 target lesion that is unirradiated and measurable by RECIST, Version 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
* Adequate organ function

Exclusion Criteria

* Prior chemotherapy for extensive-stage SCLC
* 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 4 weeks prior to enrollment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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G1 Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Contact

Role: STUDY_DIRECTOR

G1 Therapeutics, Inc.

Locations

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Genesis Cancer Center

Hot Springs, Arkansas, United States

Site Status

Highlands Oncology Group

Rogers, Arkansas, United States

Site Status

The Oncology Institute of Hope and Innovation

Whittier, California, United States

Site Status

Memorial Hospital - Univ. of Colorado Health

Colorado Springs, Colorado, United States

Site Status

University of Colorado Health, Oncology Clinical Research Northern Region

Fort Collins, Colorado, United States

Site Status

Boca Raton Regional Hospital - Lynn Cancer Institute

Boca Raton, Florida, United States

Site Status

Florida Cancer Specialists - South

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists - North

Tavares, Florida, United States

Site Status

Florida Cancer Specialists - East

West Palm Beach, Florida, United States

Site Status

University Cancer and Blood Center, LLC

Athens, Georgia, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Center For Cancer and Blood Disorders

Bethesda, Maryland, United States

Site Status

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Site Status

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, United States

Site Status

Roswell Park

Buffalo, New York, United States

Site Status

UNC - Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Oklahoma University - Peggy and Charles Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Guthrie Medical Group, PC

Sayre, Pennsylvania, United States

Site Status

Greenville Health System

Greenville, South Carolina, United States

Site Status

Gibbs Cancer Center

Spartanburg, South Carolina, United States

Site Status

Tennessee Cancer Specialists

Knoxville, Tennessee, United States

Site Status

Hanna Cancer Associates - University of Tennessee

Knoxville, Tennessee, United States

Site Status

Texas Oncology

Tyler, Texas, United States

Site Status

Northwest Cancer Specialists, P.C.

Vancouver, Washington, United States

Site Status

CHU de Rennes Hopital Pontchaillou

Rennes, , France

Site Status

ARENSIA Exploratory Medicine LLC

Tbilisi, , Georgia

Site Status

Veszprem Megyei Tudogyogyintezet

Farkasgyepű, Veszprém megye, Hungary

Site Status

Orszagos Koranyi Tbc es Pulmonologiai Intezet, XI. Tudobelosztaly

Budapest, , Hungary

Site Status

Hetenyi Geza Korhaz

Szolnok, , Hungary

Site Status

ARENSIA Exploratory Medicine Phase I Unit, The Institute of Oncology

Chisinau, , Moldova

Site Status

Samodzielny Publiczny ZespAA GruAicy i ChorAb PA¿uc

Olsztyn, , Poland

Site Status

Wojewodzki Szpital Zespolony im. L. Rydygiera

Torun, , Poland

Site Status

Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie

Warsaw, , Poland

Site Status

Hospital Regional Universitario HRU Carlos Haya Malaga

Málaga, Andalusia, Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Consorcio Hospitalario Provincial

Castillón, , Spain

Site Status

Hgu Gregorio Maranon

Madrid, , Spain

Site Status

Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

Countries

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United States France Georgia Hungary Moldova Poland Spain

References

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Hussein M, Maglakelidze M, Richards DA, Sabatini M, Gersten TA, Lerro K, Sinielnikov I, Spira A, Pritchett Y, Antal JM, Malik R, Beck JT. Myeloprotective Effects of Trilaciclib Among Patients with Small Cell Lung Cancer at Increased Risk of Chemotherapy-Induced Myelosuppression: Pooled Results from Three Phase 2, Randomized, Double-Blind, Placebo-Controlled Studies. Cancer Manag Res. 2021 Aug 9;13:6207-6218. doi: 10.2147/CMAR.S313045. eCollection 2021.

Reference Type DERIVED
PMID: 34408488 (View on PubMed)

Ferrarotto R, Anderson I, Medgyasszay B, Garcia-Campelo MR, Edenfield W, Feinstein TM, Johnson JM, Kalmadi S, Lammers PE, Sanchez-Hernandez A, Pritchett Y, Morris SR, Malik RK, Csoszi T. Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy-induced myelosuppression in patients with small cell lung cancer: Pooled analysis of three randomized phase 2 trials. Cancer Med. 2021 Sep;10(17):5748-5756. doi: 10.1002/cam4.4089. Epub 2021 Aug 18.

Reference Type DERIVED
PMID: 34405547 (View on PubMed)

Li C, Hart L, Owonikoko TK, Aljumaily R, Rocha Lima CM, Conkling PR, Webb RT, Jotte RM, Schuster S, Edenfield WJ, Smith DA, Sale M, Roberts PJ, Malik RK, Sorrentino JA. Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer. Cancer Chemother Pharmacol. 2021 May;87(5):689-700. doi: 10.1007/s00280-021-04239-9. Epub 2021 Feb 17.

Reference Type DERIVED
PMID: 33595690 (View on PubMed)

Lai AY, Sorrentino JA, Dragnev KH, Weiss JM, Owonikoko TK, Rytlewski JA, Hood J, Yang Z, Malik RK, Strum JC, Roberts PJ. CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy. J Immunother Cancer. 2020 Oct;8(2):e000847. doi: 10.1136/jitc-2020-000847.

Reference Type DERIVED
PMID: 33004541 (View on PubMed)

Weiss JM, Csoszi T, Maglakelidze M, Hoyer RJ, Beck JT, Domine Gomez M, Lowczak A, Aljumaily R, Rocha Lima CM, Boccia RV, Hanna W, Nikolinakos P, Chiu VK, Owonikoko TK, Schuster SR, Hussein MA, Richards DA, Sawrycki P, Bulat I, Hamm JT, Hart LL, Adler S, Antal JM, Lai AY, Sorrentino JA, Yang Z, Malik RK, Morris SR, Roberts PJ, Dragnev KH; G1T28-02 Study Group. Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019 Oct 1;30(10):1613-1621. doi: 10.1093/annonc/mdz278.

Reference Type DERIVED
PMID: 31504118 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-001583-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

G1T28-02

Identifier Type: -

Identifier Source: org_study_id

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