Advanced Malignant Solid Neoplasm Clinical Trial
Official title:
A Phase II Basket Trial of Glutaminase Inhibitor (BEGIN) Telaglenastat (CB-839) HCL in Patients With NF1 Aberrations, NF1 Mutant Malignant Peripheral Nerve Sheath Tumors (MPNST), KEAP1/NRF2 and LKB1 Aberrant Tumors
This phase II trial studies how well glutaminase inhibitor telaglenastat hydrochloride (CB-839 HCl) works in treating patients with specific genetic mutations and solid tumors or malignant peripheral nerve sheath tumors that have spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Glutaminase converts an amino acid (building block of proteins) called glutamine to glutamate, which can support several cellular pathways. Telaglenastat hydrochloride works by blocking glutamine activity needed for the growth of cells. When this activity is blocked, the growth of cancer cells may stop and the cancer cells may then die. Cancer is caused by changes (mutations) to genes that control the way cells function and uncontrolled cell growth may result in tumor formation. Specific genetic mutations studied in this clinical trial are NF1 mutation for malignant peripheral nerve sheath tumors, and NF1, KEAP1/NRF2, or STK11/LKB1 mutation for other solid tumors. Telaglenastat hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVE: I. To assess the best overall response rate (BORR) achieved by 6 months of telaglenastat (CB-839) hydrochloride (HCl) treatment in specific pathway aberrant tumors (MPNST, NF1, KEAP1/NRF2 & STK11/ LKB1). SECONDARY OBJECTIVES: I. To determine the safety, progression-free survival (PFS), time to progression (TTP) and overall survival (OS). II. To determine the overall response rate (ORR) (highest objective response achieved between start of therapy and progression), time to response (TTR) and clinical benefit rate (CBR) of telaglenastat (CB-839)HCl. III. To assess pharmacodynamic changes and adaptive responses and correlate with response to treatment as well as disease progression (correlative objective). EXPLORATORY OBJECTIVES: I. Correlate fludeoxyglucose F-18 (18-F FDG) positron emission tomography (PET)/computed tomography (CT) pre-therapy and 8-weeks post-therapy response to telaglenastat (CB-839) HCl therapy. II. Evaluate changes in level of circulating tumor deoxyribonucleic acid (DNA) at baseline, one month on-treatment and time of progression (Molecular Characterization Laboratory [MoCHA Labs]) to treatment response. III. Quantify the peripheral blood concentrations of the metabolites: aspartate, glutamate, glutamine and arginine (@Mayo clinic Oncometabolomics core) and correlate with response. IV. Evaluate the pharmacodynamic (PD) effect of telaglenastat (CB-839) HCl on systemic levels of the tricarboxylic acid (TCA) cycle metabolites in peripheral blood (baseline and one month) as part of the protocol. V. Evaluate tumor by reverse phase protein array (@core facility at MD Anderson) and ribonucleic acid (RNA) sequencing (seq) to evaluate changes from pre-treatment, during treatment and post treatment specimens. VI. Perform patient-derived tumor xenograft (PDX) modelling-co-clinical trials (@Dr. Funda Meric-Bernstam's lab MD Anderson) to understand response/resistance mechanisms and also evaluate combination therapies for future development. OUTLINE: Patients receive telaglenastat hydrochloride orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, magnetic resonance imaging (MRI), or PET/CT during screening and on study, and collection of blood samples during screening and on study. After completion of study treatment, patients are followed up every 3 months thereafter. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05039801 -
IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors
|
Phase 1 | |
| Completed |
NCT02317874 -
Testing the Addition of the Anti-Cancer Drug Talazoparib to the Combination of Carboplatin and Paclitaxel for the Treatment of Advanced Cancer
|
Phase 1 | |
| Recruiting |
NCT05691491 -
Testing the Combination of the Anti-Cancer Drugs Temozolomide and M1774 to Evaluate Their Safety and Effectiveness
|
Phase 1/Phase 2 | |
| Active, not recruiting |
NCT03218826 -
PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery
|
Phase 1 | |
| Withdrawn |
NCT03925428 -
Testing a New Anti-cancer Drug Combination, Entinostat and GSK525762C, for Advanced and Refractory Solid Tumors and Lymphomas
|
Phase 1 | |
| Active, not recruiting |
NCT03233204 -
Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
|
Phase 2 | |
| Active, not recruiting |
NCT04294628 -
Testing the Biological Effects of DS-8201a on Patients With Advanced Cancer
|
Phase 1 | |
| Active, not recruiting |
NCT02389309 -
Dasatinib, Temsirolimus, and Cyclophosphamide in Treating Patients With Advanced, Recurrent, or Refractory Solid Tumors
|
Phase 1 | |
| Active, not recruiting |
NCT03065387 -
Neratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and Advanced or Metastatic Solid Tumors With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation
|
Phase 1 | |
| Terminated |
NCT04552704 -
CD24Fc for the Treatment of Immune Related Adverse Events in Patients With Advanced Solid Tumors, TIRAEC Study
|
Phase 1/Phase 2 | |
| Active, not recruiting |
NCT03213691 -
Selumetinib Sulfate in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
|
Phase 2 | |
| Recruiting |
NCT02408861 -
Nivolumab and Ipilimumab in Treating Patients With HIV Associated Relapsed or Refractory Classical Hodgkin Lymphoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
|
Phase 1 | |
| Recruiting |
NCT05638295 -
Testing the Use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial)
|
Phase 2 | |
| Recruiting |
NCT05455606 -
Does the Use of a Genomic Tumor Board Increase the Number of Patients Who Receive Genome-Informed Treatment
|
N/A | |
| Recruiting |
NCT05101356 -
A Cancer Vaccine (Labvax 3(22)-23) and GM-CSF Alone or in Combination With Pembrolizumab for the Treatment of Advanced Stage Adenocarcinoma
|
Phase 1/Phase 2 | |
| Active, not recruiting |
NCT03220035 -
Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
|
Phase 2 | |
| Completed |
NCT02451553 -
Afatinib Dimaleate and Capecitabine in Treating Patients With Advanced Refractory Solid Tumors, Pancreatic Cancer or Biliary Cancer
|
Phase 1 | |
| Active, not recruiting |
NCT03213678 -
Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
|
Phase 2 | |
| Active, not recruiting |
NCT01480154 -
Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer
|
Phase 1 | |
| Active, not recruiting |
NCT04514484 -
Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV
|
Phase 1 |