Neratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and… (NCT03065387) | Clinical Trial Compass
Active — Not RecruitingPhase 1
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
United States93 participantsStarted 2017-10-31
Plain-language summary
This phase I trial studies the side effects and best dose of neratinib in combination with everolimus, palbociclib, or trametinib in participants with solid tumors with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation, or KRAS mutation that do not respond to treatment (refractory) and have spread to other parts of the body (advanced or metastatic). Neratinib, palbociclib, and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as everolimus, 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. Giving neratinib with everolimus, palbociclib, or trametinib may work better than neratinib alone in treating participants with solid tumors.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Subjects with advanced or metastatic solid tumors that are refractory to standard therapies known to provide clinical benefit. Subjects with hematologic malignancy including lymphoma/myeloma will not be enrolled on this study.
✓. Subjects must have one of the following:
✓. somatic mutations in human epidermal growth factor receptor (EGFR, HER2, HER3, and HER4)
✓. EGFR gene amplification (patients with 3+ results on immunohistochemistry testing for EGFR may be allowed to enroll if gene amplification results are unavailable)
✓. HER2 gene amplification (patients with 3+ results on immunohistochemistry testing for Her-2 may be allowed to enroll if gene amplification results are unavailable)
✓. Somatic mutation in KRAS (Patients will be enrolled only on neratinib and trametinib combination ARM).
✓. Subjects must have measurable disease by RECIST v1.1. (only for MTD Expansion Cohorts)
✓. Subjects must be ≥18 years of age.
Exclusion criteria
What they're measuring
1
Maximum tolerated dose (MTD) of neratinib when given in combination with everolimus, palbociclib, or trametinib
✕. Known Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV) infection.
✕. Inability or unwillingness to swallow pills.
✕. Active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization.
✕. Clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. For example, subjects should have no more than 50% of the large intestine removed and no sign of malabsorption (e.g. gastrectomy, ileal bypass, chronic diarrhea, Crohn's disease, malabsorption, gastroparesis).
✕. Inability to comply with the study and follow-up procedures.
✕. History of cerebrovascular accident (CVA), myocardial infarction or unstable angina within the previous 6 months before starting therapy.
✕. Prolongation of QT/QTc interval (QTc interval \>450 ms for males or \>470 ms for females) using the Fredericia method of QTc analysis. For patients with bundle branch block (BBB), the Rautaharju method of QTc analysis (QTcR) will be used.