Malignant Solid Neoplasm Clinical Trial
Official title:
Phase I Trial of DS-8201a (Trastuzumab Deruxtecan) in Combination With Neratinib in Solid Tumors With HER2 Alterations
This phase I trial tests the safety, side effects, and best dose of neratinib in combination with trastuzumab deruxtecan in treating patients with solid tumors that have spread to other parts of the body (metastatic) or that cannot be removed by surgery (unresectable), and have changes in a gene called human epidermal growth factor receptor 2 (HER2). Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Adding neratinib to trastuzumab deruxtecan may be able to shrink cancer with a change in the HER2 gene.
PRIMARY OBJECTIVE: I. To assess dose limiting toxicities and determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of neratinib maleate (neratinib) and trastuzumab deruxtecan (DS-8201a) in patients with advanced solid tumors harboring alterations in HER2 (including HER2 overexpression/amplification and selected HER2-activating mutations). SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity of neratinib and DS-8201a, as measured by objective response rate (ORR), duration of response (DoR), and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by investigator assessment, and overall survival (OS). II. To assess the safety and tolerability for the combination neratinib and DS-8201a. III. To assess the effect of neratinib on DS-8201a payload (DXd/MAAA-1181a) tissue concentration in part 2 at the RP2D chosen in part 1 (and potentially at a lower dose[s] of neratinib) before and after addition of neratinib to DS-8201a. IV. To assess the pharmacokinetics of DS-8201a and neratinib in combination. EXPLORATORY OBJECTIVES: I. To assess the pharmacodynamic response to neratinib and DS-8201a as measured by markers of DS-8201a-induced deoxyribonucleic acid (DNA) damage using gammaH2AX, phosphorylated (p)NBS1 immunofluorescence assay (IFA), multiplex multiple reaction monitoring mass spectrometry (MRM)- based proteomic assay panel of DNA repair response pathway biomarkers, induction of apoptosis, and HER2 signaling along with other pharmacodynamic (PD) biomarkers such as cleaved caspase3 (apoptosis) and TOP1CC (target engagement) pending National Clinical Laboratory Network (NCLN) assay availability. II. To assess quantifiable HER2 protein expression of pre-treatment or archival tumor biopsies, and at disease progression in correlation with treatment response. III. To assess tumor tissue mutation profile pre-treatment and at progression in correlation with treatment response. IV. To assess circulating cell-free DNA (cfDNA) mutation profiles pre-treatment, C2D1, and at progression in correlation with treatment response. OUTLINE: This is a dose-escalation study of neratinib followed by a dose-expansion (PD) study. Patients receive neratinib orally (PO) once daily (QD) on days 1-21 (days 8-21 of cycle 1, then days 1-21 in cycles thereafter for PD study) of each cycle and trastuzumab deruxtecan intravenously (IV) over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, computed tomography (CT) scan and echocardiograpahy or multigated acquisition (MUGA) scan throughout study. Additionally, patients may undergo a tissue biopsy at baseline. After completion of study treatment, patients are followed up every 3 months for at least one year or until death. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT06030427 -
Virtual Mindfulness and Weight Management to Mitigate Risk of Relapse and Improve Wellbeing in Cancer Survivors
|
N/A | |
Completed |
NCT04337203 -
Shared Healthcare Actions and Reflections Electronic Systems in Survivorship
|
N/A | |
Recruiting |
NCT05660421 -
Itacitinib for the Treatment Steroid Refractory Immune Related Adverse Events Arising From Immune Checkpoint Inhibitors
|
Phase 2 | |
Suspended |
NCT04060849 -
Nozin in Preventing Respiratory Viral Infections in Patients Undergoing Stem Cell Transplant, PREV-NOSE STUDY
|
Phase 1 | |
Recruiting |
NCT06192875 -
A Novel Molecular Approach to Blood DNA Screening for Cancer: Specificity Assessment (The NOMAD Study)
|
||
Completed |
NCT04122118 -
Pharmacist-led Transitions of Care in the Outpatient Oncology Infusion Center for Patients With Solid Tumor
|
N/A | |
Active, not recruiting |
NCT04940299 -
Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma
|
Phase 2 | |
Active, not recruiting |
NCT03168737 -
18F-Fluoroazomycin Arabinoside PET-CT in Diagnosing Solid Tumors in Patients
|
Phase 1 | |
Active, not recruiting |
NCT06062901 -
An Educational Intervention on Provider Knowledge for the Support of Cancer Survivors
|
N/A | |
Active, not recruiting |
NCT02444741 -
Pembrolizumab and Stereotactic Body Radiation Therapy or Non-Stereotactic Wide-Field Radiation Therapy in Treating Patients With Non-small Cell Lung Cancer
|
Phase 1/Phase 2 | |
Terminated |
NCT04081298 -
eHealth Diet and Physical Activity Program for the Improvement of Health in Rural Latino Cancer Survivors
|
N/A | |
Active, not recruiting |
NCT04555837 -
Alisertib and Pembrolizumab for the Treatment of Patients With Rb-deficient Head and Neck Squamous Cell Cancer
|
Phase 1/Phase 2 | |
Completed |
NCT04983901 -
PHASE II SINGLE-CENTER, RANDOMIZED, OPEN-LABEL, PROSPECTIVE, STUDY TO DETERMINE THE IMPACT OF SERIAL PROCALCITONIN
|
Phase 2 | |
Active, not recruiting |
NCT04602026 -
The RIOT Trial: Re-Defining Frailty and Improving Outcomes With Prehabilitation for Pancreatic, Liver, or Gastric Cancer
|
N/A | |
Recruiting |
NCT04871542 -
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
|
||
Active, not recruiting |
NCT04592250 -
Financial Toxicity in Cancer Patients
|
||
Recruiting |
NCT05112614 -
Role of Gut Microbiome in Cancer Therapy
|
||
Active, not recruiting |
NCT04296305 -
Effect of Opioid Infusion Rate on Abuse Liability Potential of Intravenous Hydromorphone for Cancer Pain
|
Phase 4 | |
Recruiting |
NCT05873608 -
Communication Issues in Patient and Provider Discussions of Immunotherapy
|
N/A | |
Recruiting |
NCT02464696 -
Non-invasive Ventilation in Reducing the Need for Intubation in Patients With Cancer and Respiratory Failure
|
N/A |