A Phase IB and Randomized Open-Label Phase II Study of Berzosertib (M6620, VX-970) in Combination With Carboplatin/Gemcitabine/Pembrolizumab in Patients With Chemotherapy-Naïve Advanced Non-Small Cell Lung Cancer of Squamous Cell Histology

Who is this study for? Adult patients with lung non-small cell squamous cell carcinoma
What treatments are being studied? Berzosertib
Status: Recruiting
Location: See all (33) locations...
Intervention Type: Procedure, Drug, Biological
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

This phase Ib/II trial studies the best dose of carboplatin when given together with berzosertib, gemcitabine and pembrolizumab and to see how well it works in treating patients with stage IV squamous cell non-small cell lung cancer that has spared to other placed in the body (advanced). Berzosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as carboplatin and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving berzosertib together with carboplatin, gemcitabine, and pembrolizumab may work better in treating patients with squamous cell non-small cell lung cancer compared to carboplatin, gemcitabine, and pembrolizumab alone.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

• Patients must have histologically confirmed NSCLC of predominantly squamous cell histology, stage IV (American Joint Committee on Cancer [AJCC] 8th edition)

• Patients must have measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

• Patients must have tumor tissue available at time of enrollment, or be willing to undergo a biopsy for integrated biomarker studies

• Patients with a history of prior platinum-based systemic chemotherapy given as neoadjuvant, adjuvant, or consolidation therapy for early stage or loco-regionally advanced NSCLC are eligible, if therapy is completed one year prior to initiation of treatment. Patients must not have had prior systemic chemotherapy or immunotherapy for metastatic disease

• Patients with prior immunotherapy given as neoadjuvant, adjuvant, or consolidation therapy for early stage or loco-regionally advanced disease are eligible, if treatment is completed one year prior to initiation of treatment

• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky > 60%)

• Age >= 18 years. Because no dosing or adverse event data are currently available on the use of these drug combinations in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count > lower limit of normal (LLN)

• Platelets > LLN

• Total bilirubin =< institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN

• Creatinine =< institutional ULN OR glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2

• Patients with human immunodeficiency virus (HIV) infection are eligible if they are on effective anti-retroviral therapy with undetectable viral load within 6 months, provided there is no expected drug-drug interaction

• Patients with evidence of chronic hepatitis B virus (HBV) infection are eligible if the HBV viral load is undetectable on suppressive therapy (if indicated), provided there is no expected drug-drug interaction

• Patients with a history of hepatitis C virus (HCV) infection are eligible if they have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Patients with treated brain metastases are eligible if clinically stable, i.e., on stable doses of anti-convulsant therapy and/or stable doses of corticosteroids which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better

• Patients must be willing to comply with birth control requirements: The effects of the agents in this study (or similar agents) on the developing human fetus are either unknown, or known to be teratogenic, embryotoxic, and fetotoxic in mice and rabbits. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after completing treatment administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to avoid donating sperm for during the study period, and to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after completion completing treatment administration

• Patients must have the ability to understand and willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative and/or family member available will also be eligible

Locations
United States
California
Los Angeles County-USC Medical Center
Recruiting
Los Angeles
USC / Norris Comprehensive Cancer Center
Recruiting
Los Angeles
Florida
UM Sylvester Comprehensive Cancer Center at Aventura
Recruiting
Aventura
UM Sylvester Comprehensive Cancer Center at Coral Gables
Recruiting
Coral Gables
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Recruiting
Deerfield Beach
University of Miami Miller School of Medicine-Sylvester Cancer Center
Recruiting
Miami
Kansas
University of Kansas Clinical Research Center
Active, not recruiting
Fairway
HaysMed University of Kansas Health System
Active, not recruiting
Hays
University of Kansas Cancer Center
Active, not recruiting
Kansas City
Lawrence Memorial Hospital
Active, not recruiting
Lawrence
Olathe Health Cancer Center
Active, not recruiting
Olathe
University of Kansas Cancer Center-Overland Park
Active, not recruiting
Overland Park
University of Kansas Hospital-Indian Creek Campus
Active, not recruiting
Overland Park
Ascension Via Christi - Pittsburg
Active, not recruiting
Pittsburg
Salina Regional Health Center
Active, not recruiting
Salina
University of Kansas Health System Saint Francis Campus
Active, not recruiting
Topeka
University of Kansas Hospital-Westwood Cancer Center
Active, not recruiting
Westwood
Massachusetts
Dana-Farber Cancer Institute
Withdrawn
Boston
Missouri
Siteman Cancer Center at West County Hospital
Recruiting
Creve Coeur
Truman Medical Centers
Active, not recruiting
Kansas City
University of Kansas Cancer Center - North
Active, not recruiting
Kansas City
University of Kansas Cancer Center - Lee's Summit
Active, not recruiting
Lee's Summit
University of Kansas Cancer Center at North Kansas City Hospital
Active, not recruiting
North Kansas City
Siteman Cancer Center at Christian Hospital
Recruiting
Saint Louis
Siteman Cancer Center-South County
Recruiting
Saint Louis
Washington University School of Medicine
Recruiting
Saint Louis
Siteman Cancer Center at Saint Peters Hospital
Recruiting
Saint Peters
North Carolina
Wake Forest University at Clemmons
Recruiting
Clemmons
Wake Forest University Health Sciences
Recruiting
Winston-salem
New Hampshire
Dartmouth Hitchcock Medical Center
Recruiting
Lebanon
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
Recruiting
New York
Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
Recruiting
Pittsburgh
Virginia
Virginia Commonwealth University/Massey Cancer Center
Active, not recruiting
Richmond
Time Frame
Start Date: June 1, 2020
Estimated Completion Date: August 15, 2023
Participants
Target number of participants: 106
Treatments
Experimental: Arm A (pembrolizumab, gemcitabine, carboplatin, M6620)
Patients receive pembrolizumab IV over 30 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, carboplatin IV over 30 minutes on day 1, and berzosertib IV over 60 minutes on days 2 and 9. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab IV over 30 minutes on day 1 and berzosertib IV over 60 minutes on days 2 and 9. Cycles repeat every 21 days for up to 9 months in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab alone IV over 30 minutes on day 1. Cycles repeat every 6 weeks for up to 1 more year in the absence of disease progression or unacceptable toxicity. Patients undergo MRI scans and/or CT scans, and undergo blood specimen collection on study.
Active Comparator: Arm B (pembrolizumab, gemcitabine, carboplatin)
Patients receive pembrolizumab, gemcitabine, and carboplatin as in Arm A. Patients undergo MRI scans and/or CT scans, and undergo blood specimen collection on study.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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