Phase 1
Completed N=132
Safety Study of PLX108-01 in Patients With Solid Tumors
Source: ClinicalTrials.gov NCT01004861 ↗Enrolled (actual)
132
Serious AEs
17.4%
Results posted
Apr 2020
Primary outcomePrimary: Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Escalation (Efficacy Evaluable Population) — 0; 1; 2; 0 Participants
Summary
PLX3397 is a selective inhibitor of Fms, Kit, and oncogenic Flt3 activity. The primary objective of this study is to evaluate the safety and pharmacokinetics of orally administered PLX3397 in patients with advanced, incurable, solid tumors in which these target kinases are linked to disease pathophysiology. The secondary objective is to measure the pharmacodynamic activity of PLX3397 via blood, plasma and urine biomarkers of Fms activity.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Escalation (Efficacy Evaluable Population) |
0; 1; 2; 0; 3; 0 | — |
| PRIMARY Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension (Efficacy Evaluable Population) |
0; 2; 0; 0; 0; 0 | — |
| PRIMARY Duration of Response (Efficacy Evaluable Population) - Dose Extension |
NA; 115 | — |
| PRIMARY Progression-free Survival (Efficacy Evaluable Population) - Dose Extension |
NA; NA; 54; 50; 78; 161 | — |
| PRIMARY Best Overall Tumor Response (PVNS Cohort) Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension |
2; 22; 8; 1; 4; 24 | — |
| PRIMARY Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Cmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation |
1730; 3630; 3160; 6570; 6290; 10600 | — |
| PRIMARY Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Tmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation |
2.00; 1.97; 0.98; 1.04; 2.00; 1.05 | — |
| PRIMARY Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Area Under the Curve (AUC0-24), Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation |
26200; 50400; 40500; 81000; 107000; 173000 | — |
| PRIMARY Numeric Rating Scale (NRS) for PVNS Symptoms Sum of Scores Through Cycle 2 (Efficacy Evaluable Population) - Dose Extension |
5.2; 3.5; 3.6; 2.3; 1.3; 1.5 | — |
Eligibility Criteria
Inclusion Criteria
- Age 18 and older
- Solid tumors refractory to standard therapy
- For the Extension cohorts, patients must have measurable disease by RECIST criteria and meet the following disease-specific criteria:
- For advanced or recurrent mucoepidermal carcinoma (MEC) of the salivary gland, patients must not be candidates for curative surgery or radiotherapy.
- For pigmented villo-nodular synovitis (PVNS), patients must have a histologically confirmed diagnosis of inoperable progressive or relapsing PVNS, or resectable tumor requesting mutilating surgery, as well as demonstrated progressive disease in the last 12 months.
- For gastrointestinal stromal tumors (GIST), patients must have failed previous therapy with imatinib and sunitinib. Patients with known PDGFR mutations are excluded, but mutation testing is not required for study entry.
- For anaplastic thyroid cancer (ATC), patients must have histologically or cytologically diagnosed advanced ATC.
- For metastatic solid tumors with documented malignant pleural and/or peritoneal effusions, patients must not be receiving specific therapy for the effusion or have an indwelling drain.
- Eastern Cooperative Oncology Group performance status 0 or 1
- Life expectancy >= 3 months
- Adequate hepatic, renal, and bone marrow function
Exclusion Criteria
- Specific anti-cancer therapy within 3 weeks of study start
- Uncontrolled intercurrent illness
- Refractory nausea or vomiting, or malabsorption
- Mean corrected QT interval (QTc) >= 450 msec (for males) or QTc >= 470 msec (for females)
Data sourced from ClinicalTrials.gov (NCT01004861). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.