ALRN-6924 and Paclitaxel in Treating Patients With Advanced, Metastatic, or Unresectable Solid Tu… (NCT03725436) | Clinical Trial Compass
CompletedPhase 1
ALRN-6924 and Paclitaxel in Treating Patients With Advanced, Metastatic, or Unresectable Solid Tumors
United States28 participantsStarted 2019-01-24
Plain-language summary
This phase Ib trial studies the side effects and best dose of ALRN-6924 when given together with paclitaxel in treating patients with solid tumors that have spread to other places in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as ALRN-6924 and paclitaxel, 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.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. 18 years of age or older
✓. Histologically- or cytologically-confirmed solid tumors (excluding lymphomas) that are metastatic or unresectable and that meet the following criteria:
✓. Escalation and expansion cohorts: wild type (WT) TP53 status defined as no mutation on a Clinical Laboratory Improvement Amendments (CLIA)-certified next-generation sequencing (NGS) assay that has sequenced the full length TP53 gene. Patients can be enrolled based on tissue testing or liquid biopsies. If enrolled based on liquid biopsies, testing should have detected other somatic mutations.
✓. Expansion cohort A only: estrogen receptor (ER) positive (\> 1%), human epidermal growth factor 2 (HER2) negative, WT TP53 metastatic or inoperable locally advanced or locally recurrent breast cancer regardless of progresterone receptor (PR) status, HER2 status will be defined according to the ASCO/CAP 2018 recommendationa (Patients can be HER2 0+ or 1+ by immunohistochemistry (IHC), 2+ by IHC and fluorescent in situ hybridization (FISH) non-amplified to be considered HER2 negative). Standard treatment with therapies known to confer a survival benefit does not exist, is no longer effective or tolerated, or the patient declines standard treatment. For the dose expansion cohort only, breast cancer patients with ER+, HER2- status must have received prior endocrine therapy and CDK4/6 inhibitors
✓. Expansion cohort B only: advanced or metastatic solid tumors with MDM2 or MDM4 amplifications and WT TP53 metastatic for which standard treatment with therapies known to confer a survival benefit does not exist, is no longer effective or tolerated, or the patient declines standard treatment.
✓. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. In the dose escalation stage, patients without measurable disease by RECIST 1.1, but evaluable disease are also eligible.
✓. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Section 12, Appendix A).
What they're measuring
1
Maximum tolerated dose (MTD) of combination of ALRN-6924 and paclitaxel, defined as the isotonic estimate of the toxicity rate closest to 0.30
. Demonstrate adequate organ function as defined by the parameters listed below:
Exclusion criteria
✕. Previous treatment with investigational agents that inhibit MDM2 or MDMX activity.
✕. Known active hepatitis B, hepatitis C and/or human immunodeficiency virus (HIV)-positive patients who have a cluster of differentiation 4 (CD4) count \< 200. No antiretroviral medications that are CYP3A4 substrates will be allowed.
✕. Pre-existing history of or known cardiovascular risk:
✕. History of acute coronary syndromes within 6 months prior to the first dose of ALRN-6924 (including myocardial infarction, unstable angina, coronary artery bypass graft, angioplasty, or stenting).
✕. Uncontrolled hypertension
✕. Pre-existing cardiac failure (New York Heart Association class III-IV)
✕. Corrected QTcF interval on screening ECG ≥450 msec for males and ≥470 msec for females (QTcF \>480 msec for any patient with a bundle branch block).