Testing of the Anti Cancer Drugs CB-839 HCl (Telaglenastat) and MLN0128 (Sapanisertib) in Advanced Stage Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT04250545|
Recruitment Status : Recruiting
First Posted : January 31, 2020
Last Update Posted : February 25, 2021
|Condition or disease||Intervention/treatment||Phase|
|Leptomeningeal Neoplasm Metastatic Lung Non-Small Cell Carcinoma Metastatic Malignant Neoplasm in the Brain Recurrent Lung Non-Small Cell Carcinoma Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8||Drug: Sapanisertib Drug: Telaglenastat Hydrochloride||Phase 1|
I. To determine the safety and tolerability of glutaminase inhibitor CB-839 hydrochloride (CB-839 HCl) (telaglenastat) in combination with MLN0128 (sapanisertib) and determine the recommended phase 2 dose (RP2D) of the combination.
I. To observe and record anti-tumor activity. II. To examine preliminary efficacy of CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib) in squamous cell lung cancers (LSCC) and in select, molecularly-defined non-small cell lung cancer (NSCLC) cohorts.
IIa. To evaluate the objective response rate (ORR), progression-free survival (PFS), and disease control rate (DCR) of patients treated with CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib).
I. To correlate genomic and metabolomic signatures with response. II. To evaluate metabolic response (18Glutamine [GLN]-positron emission tomography [PET]/computed tomography [CT]; 18Fluorodeoxyglucose [FDG]-PET/CT) in NSCLC tumors treated with CB-839 HCl (telaglenastat) and MLN0128 (sapanisertib) in the dose expansion.
OUTLINE: This is a dose-escalation study of glutaminase inhibitor CB-839 hydrochloride.
Patients receive glutaminase inhibitor CB-839 hydrochloride orally (PO) twice daily (BID) and sapanisertib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up quarterly.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||85 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Trial of MLN0128 (Sapanisertib) and CB-839 HCl (Telaglenastat) in Advanced NSCLC Patients|
|Actual Study Start Date :||June 12, 2020|
|Estimated Primary Completion Date :||September 30, 2022|
|Estimated Study Completion Date :||September 30, 2022|
Experimental: Treatment (CB-839 HCl, sapanisertib)
Patients receive glutaminase inhibitor CB-839 hydrochloride PO BID and sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Telaglenastat Hydrochloride
- Maximum tolerated dose/recommended phase II dose of MLN0128 (sapanisertib) and CB-839 HCl (telaglenastat) in combination (dose-escalation) [ Time Frame: Up to 28 days ]Will be evaluated according to dose-limiting toxicities during cycle 1 graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
- Response rate (dose-expansion) [ Time Frame: Up to 27 months ]Response rate will be calculated for each cohort along with an exact 95% confidence interval.
- Median progression free survival (PFS) (dose-expansion) [ Time Frame: Up to 27 months ]Median PFS will be determined using the Kaplan-Meier method individual for each cohort and for all patients as well.
- Objective response rate (ORR) [ Time Frame: Up to 27 months ]ORR will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
- PFS [ Time Frame: Up to 27 months ]Will be evaluated by Kaplan-Meier estimates.
- Disease control rate (DCR) [ Time Frame: Up to 27 months ]DCR will be assessed by RECIST 1.1 criteria.
- Metabolic response (18Glutamine [GLN]-positron emission tomography [PET]/computed tomography [CT]; 18Fluorodeoxyglucose [FDG]-PET/CT) [ Time Frame: Up to 27 months ]Change in tumor uptake of radio-labelled glutamine on PET from baseline to cycle 1 day 8 will be quantified by the standardized uptake value maximum (SUVmax) (a standard PET parameter) in the largest measurable lesion. The before and after 18F-Gln PET values will be compared using log(after/before) as a measure of relative change.
- Genomic and metabolic signatures [ Time Frame: Up to 27 months ]Genomic and metabolic signatures will be correlated with responses. Changes in glutamine, glutamate, aspartate, and asparagine will be measured, and responders will be compared to non-responders using a two-sample t-test or Wilcoxon test.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04250545
|United States, California|
|City of Hope Comprehensive Cancer Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Site Public Contact 800-826-4673 email@example.com|
|Principal Investigator: Erminia Massarelli|
|University of California Davis Comprehensive Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Site Public Contact 916-734-3089|
|Principal Investigator: Jonathan W. Riess|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Site Public Contact 212-639-7592|
|Principal Investigator: Paul K. Paik|
|Principal Investigator:||Jonathan W Riess||City of Hope Comprehensive Cancer Center LAO|