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

NCT02499770 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: G1T28-022016-001583-11
• Study Type: interventional
• Target: 122
• Locations: 7 countries
• Sites: 40

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 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.

Conditions

Small Cell Lung Cancer

Keywords

Small Cell Lung Cancer; CDK 4/6 Inhibitor

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicities by Cohort in Cycle 1, Part 1

  Dose-limiting toxicities (DLTs) were drug-related toxicities defined as follows: 1. Absolute neutrophil count (ANC) \< 0.5 × 10\^9/L lasting for ≥ 7 days 2. ≥ Grade 3 neutropenic infection/febrile neutropenia 3. Grade 4 thrombocytopenia (TCP) or ≥ Grade 3 TCP with bleeding 4. Unable to start next cycle of chemotherapy due to lack of recovery to an ANC ≥ 1.5 × 10\^9/L and platelet count ≥ 100 × 10\^9/L 5. ≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for \> 72 hours) Toxicities not clearly related to etoposide/carboplatin therapy were also considered for the purposes of determining DLTs.

  Days 1-21 of Cycle 1

• Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related AEs, Related SAEs, and AEs Leading to Study Drug Discontinuation in Part 1

  An AE was defined as any untoward medical occurrence in a participant administered a medicinal product that did not necessarily have a causal relationship with this treatment. TEAEs were defined as any AE that started on or after the first dose of study drug and up to the last dose +30 days. SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. Relatedness to study drug was assessed by the investigator. Related refers to those events that were Possibly, Probably, or Definitely Related. AEs with an unknown/not reported onset date were also included.

  TEAEs were any AE that started on or after the first dose of study drug and up to the last dose +30 days (a minimum of 51 days up to a maximum of 374 days)

• Duration of Severe (Grade 4) Neutropenia in Part 2

  Severe (Grade 4) neutropenia was defined as at least 1 ANC value \<0.5 × 10\^9/L during the treatment period. Within each cycle, the duration (days) of severe neutropenia was defined as the number of days from the date of the first ANC value of \<0.5 × 10\^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10\^9/L that met the following criteria: 1) occurred after the ANC value of \<0.5 × 10\^9/L and 2) no other ANC values \<0.5 × 10\^9/L occurred between this day and end of cycle. The duration of severe neutropenia only included participants who had at least 1 severe neutropenia event in the cycle, and censoring rules were applied for unresolved severe neutropenia in a cycle. For the treatment period, the overall duration of severe neutropenia was the median value among the durations from all cycles.

  From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

Secondary Outcomes (49)

• Maximum Observed Plasma Concentration (Cmax) of Trilaciclib in Cycle 1, Part 1

  Days 1 and 3 of Cycle 1 for a 21-day cycle

• Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Trilaciclib in Cycle 1, Part 1

  Days 1 and 3 of Cycle 1 for a 21-day cycle

• Time of Maximum Observed Concentration (Tmax) of Trilaciclib in Cycle 1, Part 1

  Days 1 and 3 of Cycle 1 for a 21-day cycle

• Cmax of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1

  Days 1 and 3 of Cycle 1 for a 21-day cycle (carboplatin was only dosed on Day 1 so there are no Day 3 Cmax values)

• AUC0-inf of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1

  Days 1 and 3 of Cycle 1 for a 21-day cycle (carboplatin was only dosed on Day 1 so there are no Day 3 AUC0-inf values)

Study Arms (2)

trilaciclib + carboplatin/etoposide

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Trilaciclib; Drug: Etoposide

trilaciclib/placebo + carboplatin/etoposide

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Placebo; Drug: Trilaciclib; Drug: Etoposide

Interventions

Carboplatin DRUG

Also known as: Paraplatin

trilaciclib + carboplatin/etoposide; trilaciclib/placebo + carboplatin/etoposide

Placebo DRUG

trilaciclib/placebo + carboplatin/etoposide

Trilaciclib DRUG

Also known as: G1T28

trilaciclib + carboplatin/etoposide; trilaciclib/placebo + carboplatin/etoposide

Etoposide DRUG

Also known as: VP-16, Toposar

trilaciclib + carboplatin/etoposide; trilaciclib/placebo + carboplatin/etoposide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• G1 Therapeutics, Inc.: lead

Study Sites (40)

Genesis Cancer Center

Hot Springs, Arkansas, 71913, United States

Location

Highlands Oncology Group

Rogers, Arkansas, 72758, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

Location

Memorial Hospital - Univ. of Colorado Health

Colorado Springs, Colorado, 80909, United States

Location

University of Colorado Health, Oncology Clinical Research Northern Region

Fort Collins, Colorado, 80528, United States

Location

Boca Raton Regional Hospital - Lynn Cancer Institute

Boca Raton, Florida, 33486, United States

Location

Florida Cancer Specialists - South

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists - North

Tavares, Florida, 32778, United States

Location

Florida Cancer Specialists - East

West Palm Beach, Florida, 33401, United States

Location

University Cancer and Blood Center, LLC

Athens, Georgia, 30607, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Center For Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

Roswell Park

Buffalo, New York, 14263, United States

Location

UNC - Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27514, United States

Location

Oklahoma University - Peggy and Charles Stephenson Cancer Center

Oklahoma City, Oklahoma, 73117, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Guthrie Medical Group, PC

Sayre, Pennsylvania, 18840, United States

Location

Greenville Health System

Greenville, South Carolina, 29605, United States

Location

Gibbs Cancer Center

Spartanburg, South Carolina, 29203, United States

Location

Tennessee Cancer Specialists

Knoxville, Tennessee, 37909, United States

Location

Hanna Cancer Associates - University of Tennessee

Knoxville, Tennessee, 37920, United States

Location

Texas Oncology

Tyler, Texas, 75702, United States

Location

Northwest Cancer Specialists, P.C.

Vancouver, Washington, 98684, United States

Location

CHU de Rennes Hopital Pontchaillou

Rennes, 35033, France

Location

ARENSIA Exploratory Medicine LLC

Tbilisi, 0112, Georgia

Location

Veszprem Megyei Tudogyogyintezet

Farkasgyepű, Veszprém megye, 8582, Hungary

Location

Orszagos Koranyi Tbc es Pulmonologiai Intezet, XI. Tudobelosztaly

Budapest, 1121, Hungary

Location

Hetenyi Geza Korhaz

Szolnok, 5000, Hungary

Location

ARENSIA Exploratory Medicine Phase I Unit, The Institute of Oncology

Chisinau, 2025, Moldova

Location

Samodzielny Publiczny ZespAA GruAicy i ChorAb PA¿uc

Olsztyn, 10-357, Poland

Location

Wojewodzki Szpital Zespolony im. L. Rydygiera

Torun, 87-100, Poland

Location

Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie

Warsaw, 02-781, Poland

Location

Hospital Regional Universitario HRU Carlos Haya Malaga

Málaga, Andalusia, 29010, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Consorcio Hospitalario Provincial

Castillón, 12002, Spain

Location

Hgu Gregorio Maranon

Madrid, 28009, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Related Publications (5)

• 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.

  PMID: 34408488 DERIVED

• 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.

  PMID: 34405547 DERIVED

• 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.

  PMID: 33595690 DERIVED

• 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.

  PMID: 33004541 DERIVED

• 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.

  PMID: 31504118 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Carboplatin; trilaciclib; Etoposide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Chandra Lovejoy
• Organization: G1 Therapeutics

clovejoy@g1therapeutics.com

001 9192991250

Study Officials

• Clinical Contact

  G1 Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 16, 2015
• Study Start: June 26, 2015
• Primary Completion: July 3, 2017
• Study Completion: February 22, 2019
• Last Updated: August 21, 2020
• Results First Posted: July 9, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

GE (1); MO (1); PL (3); ES (5); US (26); HU (3); FR (1)