Metastatic Malignant Solid Neoplasm Clinical Trial
Official title:
A Phase 1 Study of the Polymerase Theta (POLQ) Inhibitor Novobiocin in BRCA-Mutant and Other DNA Damage Repair-Deficient Solid Tumors
This phase I trial tests the safety, side effects, and best dose of novobiocin in treating cancer patients with alterations in deoxyribonucleic acid (DNA) repair genes. Novobiocin is an antibiotic that blocks the activity of a protein called DNA polymerase theta, which helps repair DNA that has become damaged as cells grow and divide. Cancer cells that cannot repair their damaged DNA die. This medication may help shrink or stabilize cancer with a mutation in DNA repair genes.
PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of continuous novobiocin sodium (novobiocin) in patients with solid tumors carrying homologous recombination (HR) or DNA damage repair (DDR) alterations that are poly (ADP-ribose) polymerase (PARP) inhibitor-naïve or -resistant. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate the safety and tolerability of continuous novobiocin in patients with solid tumors carrying HR or DDR alterations that are PARP inhibitor-naïve or -resistant. III. To characterize the pharmacokinetic parameters of continuous novobiocin administration in patients with solid tumors carrying HR or DDR alterations that are PARP inhibitor-naïve or -resistant. IV. To determine the minimally biologically effective dose of novobiocin in patients with solid tumors carrying HR or DDR alterations that are PARP inhibitor-naïve or -resistant using pre- and on-treatment biopsies to characterize novobiocin-mediated pharmacodynamic effects. V. To conduct a preliminary assessment of anti-tumor activity of novobiocin administered daily. EXPLORATORY OBJECTIVES: I. Whole exome sequencing (WES) of pre- and time-of-progression biopsies to characterize tumors for HR deficiency (deleterious mutations/deletions in genes known to be involved in HR) and genomic changes mediating acquired resistance to novobiocin. II. Ribonucleic acid sequencing (RNAseq) on pre- and on-treatment biopsies, as well as time-of-progression biopsies for serial analysis of gene expression to identify determinants of response, resistance, and pathway adaptation to novobiocin. III. Correlation of baseline level of POLQ messenger (m)RNA with clinical outcome (complete response [CR], partial response [PR] or stable disease [SD] versus [vs.] progressive disease [PD]). IV. Correlation of ATM immunohistochemistry (IHC) with clinical outcome in patients with ATM-mutant cancers. OUTLINE: This is a dose-escalation study. Patients receive novobiocin sodium orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy at baseline, on day 15 of cycle 1, and at time of progression. Patients undergo medical imaging scans at baseline and every 8 weeks. Patients also undergo blood sample collection on study. After completion of study treatment, patients are followed up every 3-6 months for 2 years. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| 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 |
NCT04539574 -
An Investigational Scan (7T MRI) for the Imaging of Central Nervous System Tumors
|
N/A | |
| Not yet recruiting |
NCT05095948 -
Improving Processes of Cancer Care Delivery at a Comprehensive Cancer Center
|
||
| 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 | |
| Recruiting |
NCT05554380 -
Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With AKT Mutations, A ComboMATCH Treatment Trial
|
Phase 2 | |
| Recruiting |
NCT04957615 -
Nivolumab for the Treatment of Metastatic or Unresectable Solid Tumors With ARID1A Mutation and CXCL13 Expression
|
Phase 2 | |
| Active, not recruiting |
NCT04294628 -
Testing the Biological Effects of DS-8201a on Patients With Advanced Cancer
|
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 | |
| Withdrawn |
NCT04820894 -
Perception of Cure Among Patients With Metastatic Cancer
|
||
| Completed |
NCT03229278 -
Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma
|
Phase 1 | |
| 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 | |
| Active, not recruiting |
NCT04514497 -
Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer
|
Phase 1 | |
| Recruiting |
NCT04673448 -
Niraparib and TSR-042 for the Treatment of BRCA-Mutated Unresectable or Metastatic Breast, Pancreas, Ovary, Fallopian Tube, or Primary Peritoneal Cancer
|
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 | |
| Recruiting |
NCT04960787 -
Financial Navigation Program to Improve Understanding and Management of Financial Aspects of Cancer Care for Patients and Their Spouses
|
N/A | |
| Recruiting |
NCT05803382 -
Testing the Addition of an Anti-Cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment (Capecitabine) for Metastatic or Unresectable Cancers
|
Phase 1 | |
| Active, not recruiting |
NCT02143401 -
Navitoclax and Sorafenib Tosylate in Treating Patients With Relapsed or Refractory Solid Tumors
|
Phase 1 |