Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of tazemetostat hydrobromide (tazemetostat) in combination with topotecan hydrochloride (topotecan) and pembrolizumab in patients with recurrent extensive stage-small cell lung cancer (ES-SCLC), by reviewing dose-limiting toxicities (DLTs) in cycle 1 (21 days). (Dose-Escalation Cohort) II. To select the recommended phase II dose (RP2D) for a combination of tazemetostat, topotecan and pembrolizumab, based on pharmacodynamic (PD) parameters as well as overall efficacy and tolerability. (Dose-Escalation Cohort) III. To evaluate safety and tolerability of tazemetostat in combination with topotecan and pembrolizumab. (Expansion Cohort) SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To determine in a very preliminary fashion, the efficacy of a combination of tazemetostat, topotecan and pembrolizumab in recurrent ES-SCLC by assessing overall response rate (ORR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS). EXPLORATORY OBJECTIVES: I. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to ribonucleic acid (RNA) sequencing (RNA-Seq). II. To assess modulation of EZH2 targets including SLFN11 and MHC among others. III. To identify potential predictive biomarkers of response. IV. To identify mechanisms of drug sensitivity and resistance using deoxyribonucleic acid (DNA)- and RNA-based assessment platforms. V. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome. VI. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the National Cancer Institute (NCI) Early-Phase and Experimental Clinical Trials Biospecimen Bank (EET Biobank) at Nationwide Children's Hospital. VII. Characterize circulating cell-free DNA (cfDNA). OUTLINE: This is a dose-escalation study of tazemetostat followed by a dose-expansion study. Patients receive tazemetostat orally (PO) twice daily (BID) on days 1-21, pembrolizumab intravenously (IV) over 30 minutes on day 1, and topotecan IV over 30 minutes on days 1-5. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan throughout the study and may also undergo biopsy and collection of blood on study. After completion of study treatment, patients are followed every 3 months after removal from study treatment until study closure or death, whichever occurs first. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05353439
Study type Interventional
Source National Cancer Institute (NCI)
Contact
Status Recruiting
Phase Phase 1
Start date July 27, 2022
Completion date April 1, 2025

See also
  Status Clinical Trial Phase
Withdrawn NCT05161533 - Hypofractionated Radiation Therapy After Durvalumab and Chemotherapy for the Treatment of Stage IV Extensive Stage Small Cell Lung Cancer, CASPIAN-RT Trial Phase 2
Recruiting NCT04155034 - S1827 (MAVERICK) Testing Whether the Use of Brain Scans Alone Instead of Brain Scans Plus Preventive Brain Radiation Affects Lifespan in Patients With Small Cell Lung Cancer Phase 3
Recruiting NCT04560972 - LB-100, Carboplatin, Etoposide, and Atezolizumab for the Treatment of Untreated Extensive-Stage Small Cell Lung Cancer Phase 1
Active, not recruiting NCT03382561 - Cisplatin/Carboplatin and Etoposide With or Without Nivolumab in Treating Patients With Extensive Stage Small Cell Lung Cancer Phase 2
Recruiting NCT03830918 - Niraparib, Temozolomide and Atezolizumab in Treating Patients With Advanced Solid Tumors and Extensive-Stage Small Cell Lung Cancer With a Complete or Partial Response to Platinum-Based First-Line Chemotherapy Phase 1/Phase 2
Terminated NCT02899728 - Olaparib, Cediranib Maleate, and Standard Chemotherapy in Treating Patients With Small Cell Lung Cancer Phase 2
Completed NCT00453154 - Cisplatin or Carboplatin, and Etoposide With or Without Sunitinib Malate in Treating Patients With Extensive-Stage Small Cell Lung Cancer Phase 1/Phase 2
Terminated NCT03995667 - Tumor Treating Fields (TTFields) Therapy to Manage Brain Metastases in Small Cell Lung Cancer Phase 2
Recruiting NCT05244239 - Palliative Radiotherapy With Lurbinectedin in Patients With Extensive Stage Small Cell Lung Cancer Phase 1
Active, not recruiting NCT04334941 - Testing Maintenance Therapy for Small Cell Lung Cancer in Patients With SLFN11 Positive Biomarker Phase 2
Recruiting NCT04696575 - Lamivudine in Combination With Chemoimmunotherapy for the Treatment of Extensive Stage Small Cell Lung Cancer Phase 2
Recruiting NCT04402788 - Testing the Addition of Radiation Therapy to the Usual Immune Therapy Treatment (Atezolizumab) for Extensive Stage Small Cell Lung Cancer, The RAPTOR Trial Phase 2/Phase 3
Recruiting NCT04728230 - Olaparib and Durvalumab With Carboplatin, Etoposide, and/or Radiation Therapy for the Treatment of Extensive-Stage Small Cell Lung Cancer, PRIO Trial Phase 1/Phase 2
Recruiting NCT04919382 - Temozolomide and Atezolizumab as Second or Third Line for the Treatment of Metastatic or Recurrent Small Cell Lung Cancer Phase 2
Completed NCT04229381 - Resiliency Among Older Adults Receiving Lung Cancer Treatment N/A
Active, not recruiting NCT03896503 - Randomized Trial of Topotecan With M6620, an ATR Kinase Inhibitor, in Small Cell Lung Cancers and Small Cell Cancers Outside of the Lungs Phase 2
Not yet recruiting NCT06287775 - Testing the Combination of an Anti-cancer Drug, Iadademstat, With Other Anti-cancer Drugs (Atezolizumab or Durvalumab) at Improving Outcomes for Small Cell Lung Cancer Phase 1/Phase 2
Completed NCT04631029 - Testing the Addition of an Anti-cancer Drug, Entinostat, to the Usual Chemotherapy and Immunotherapy Treatment (Atezolizumab, Carboplatin and Etoposide) for Previously Untreated Aggressive Lung Cancer That Has Spread Phase 1
Recruiting NCT06110572 - Phase I/II Trial in ES-SCLC to Enhance Response to Atezolizumab Plus Chemotherapy With Total Body Irradiation Phase 1/Phase 2
Recruiting NCT05339022 - Supportive Care Intervention (ROAR-LCT) for Patients With Stage IIIA, IIIB, and IV Lung Cancer, ROAR-LCT Trial N/A