Testing of Tazemetostat in Combination With Topotecan and Pembrolizumab in Patients With Recurrent Small Cell Lung Cancer
Phase I Dose Escalation and Expansion Study of Tazemetostat in Combination With Topotecan and Pembrolizumab in Recurrent Small Cell Lung Cancer
3 other identifiers
interventional
18
1 country
15
Brief Summary
This phase I trial tests the safety, side effects, and best dose of tazemetostat in combination with topotecan and pembrolizumab in treating patients with small cell lung cancer that has come back after a period of improvement (recurrent). Tazemetostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as topotecan, 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 tazemetostat in combination with topotecan and pembrolizumab may shrink or stabilize recurrent small cell lung cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jul 2022
Longer than P75 for phase_1
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 23, 2022
CompletedFirst Posted
Study publicly available on registry
April 29, 2022
CompletedStudy Start
First participant enrolled
July 27, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 11, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 13, 2027
ExpectedApril 13, 2026
March 1, 2026
3.5 years
April 23, 2022
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose (dose-escalation cohort)
Up to 21 days (cycle 1)
Incidence of adverse events (expansion cohort)
Will be evaluated in more detail by reporting the adverse events noted, by type and grade, for the patients in the expansion cohort.
Up to 3 years
Secondary Outcomes (4)
Overall response rate
Up to 3 years
Progression-free survival
From the on-study date until the date of progression or death without progression, assessed up to 3 years
Overall survival
From the on-study date until the date of death or last follow-up, assessed up to 3 years
Duration of response
From the first date of response to the date of progression, assessed up to 3 years
Study Arms (1)
Treatment (tazemetostat, pembrolizumab, topotecan)
EXPERIMENTALPatients receive tazemetostat PO BID for 7 days prior to cycle 1 and then on days 1-21 of each cycle, pembrolizumab IV over 30 minutes on day 1 of each cycle, and topotecan IV over 30 minutes on days 1-3 or days 1-5 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan throughout the study and undergo biopsy and collection of blood on study.
Interventions
Undergo biopsy
Undergo collection of blood
Undergo CT scan
Given IV
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- Patients enrolled to the primary cohort must have limited- or extensive-disease SCLC at diagnosis, with relapse at study entry with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and with prior therapy with platinum doublet. Patients with extensive stage disease should have received chemo-immunotherapy. Both platinum-sensitive and platinum-resistant patients will be included
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of pembrolizumab in combination with tazemetostat and topotecan in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 70%)
- Leukocytes \>= 3000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L
- Total bilirubin =\< 1.5 institutional upper limit of normal (ULN) OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 × ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN
- Creatinine =\< 1.5 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
- Note: Creatinine clearance (CrCl) should be calculated per institutional standard. Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl
- International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
- Activated (a)PTT =\< 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load (CD4 count of greater than 250 cells/mcL) within 6 months are eligible for this trial. They must not be receiving prophylactic therapy for an opportunistic infection
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- +5 more criteria
You may not qualify if:
- Patients who have had chemotherapy, immune checkpoint inhibitors, or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
- Note: Patients who have had palliative radiotherapy may be included as long as they have recovered from any radiotherapy related adverse events (allow at least 3 days between radiotherapy completion and study treatment)
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1).
- Note: Patients with =\< grade 2 neuropathy or =\< grade 2 alopecia are an exception to this criterion and may qualify for the study
- Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Untreated immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI)
- Patients who are receiving any other investigational agents
- Patients with symptomatic brain metastasis are not eligible due to their extremely poor prognosis and since it is unclear whether the investigational agent penetrates the blood-brain barrier. However, subjects who have had treatment for their brain metastasis and are symptomatically stable while off steroid therapy for a minimum of 7 days may be enrolled. The use of physiologic doses of corticosteroids may be approved after consultation with the study PI
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab and tazemetostat or other agents used in study
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Patients with uncontrolled intercurrent illness but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because pembrolizumab as a monoclonal antibody, and tazemetostat as a EZH2 inhibitor may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab or tazemetostat, breastfeeding should be discontinued if the mother is treated with these agents and for 1 week after the last dose of tazemetostat. These potential risks may also apply to other agents used in this study
- Has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
Keck Medicine of USC Koreatown
Los Angeles, California, 90020, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, 92663, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
NCI - Center for Cancer Research
Bethesda, Maryland, 20892, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Wake Forest University at Clemmons
Clemmons, North Carolina, 27012, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anish Thomas
National Cancer Institute LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 23, 2022
First Posted
April 29, 2022
Study Start
July 27, 2022
Primary Completion
February 11, 2026
Study Completion (Estimated)
March 13, 2027
Last Updated
April 13, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.