Clinical trial NCT01004861: Safety Study of PLX108-01 in Patients With Solid Tumors
Official title: A Phase 1 Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX3397 in Patients With Advanced, Incurable, Solid Tumors in Which the Target Kinases Are Linked to Disease Pathophysiology
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: PVNS
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Plexxikon
First posted: 2009-10-30
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


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)

Primary outcomes:
measure: Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Escalation (Efficacy Evaluable Population)
timeFrame: Every 2 months beginning Cycle 3, Day 1 until disease progression (up to approximately 30 months postdose)
measure: Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension (Efficacy Evaluable Population)
timeFrame: Every 2 months beginning Cycle 3, Day 1 until disease progression (up to approximately 30 months postdose)
measure: Duration of Response (Efficacy Evaluable Population) - Dose Extension
timeFrame: From initial response until disease progression or death, up to approximately 30 months postdose
measure: Progression-free Survival (Efficacy Evaluable Population) - Dose Extension
timeFrame: From Cycle 1 Day 1 to disease progression or death
measure: Best Overall Tumor Response (PVNS Cohort) Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension
timeFrame: Every 2 months beginning Cycle 3, Day 1 until disease progression
measure: Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Cmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation
timeFrame: Cycle 1, Day 15
measure: Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Tmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation
timeFrame: Cycle 1, Day 15
measure: Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Area Under the Curve (AUC0-24), Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation
timeFrame: Cycle 1, Day 15 (QD dosing: predose [morning] and 0.5, 1, 2, 4, and 8 hours postdose; BID dosing: predose [morning] and 1, 2, 4, and 7 hours postdose)
measure: Numeric Rating Scale (NRS) for PVNS Symptoms Sum of Scores Through Cycle 2 (Efficacy Evaluable Population) - Dose Extension
timeFrame: Baseline, Cycle 1 Day 15, Cycle 2, Cycle 3, Cycle 12, Cycle 24, Cycle 36, and Cycle 46 (each cycle was 28 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center (MSKCC)
state: New York
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology, PA (North)
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Spokane
country: United States
facility: Evergreen Hematology & Oncology
state: Washington
Study officials:
affiliation: Daiichi Sankyo
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Tap WD, Singh AS, Anthony SP, Sterba M, Zhang C, Healey JH, Chmielowski B, Cohn AL, Shapiro GI, Keedy VL, Wainberg ZA, Puzanov I, Cote GM, Wagner AJ, Braiteh F, Sherman E, Hsu HH, Peterfy C, Gelhorn HL, Ye X, Severson P, West BL, Lin PS, Tong-Starksen S. Results from Phase I Extension Study Assessing Pexidartinib Treatment in Six Cohorts with Solid Tumors including TGCT, and Abnormal CSF1 Transcripts in TGCT. Clin Cancer Res. 2022 Jan 15;28(2):298-307. doi: 10.1158/1078-0432.CCR-21-2007. Epub 2021 Oct 29.
citation: Lewis JH, Gelderblom H, van de Sande M, Stacchiotti S, Healey JH, Tap WD, Wagner AJ, Pousa AL, Druta M, Lin CC, Baba HA, Choi Y, Wang Q, Shuster DE, Bauer S. Pexidartinib Long-Term Hepatic Safety Profile in Patients with Tenosynovial Giant Cell Tumors. Oncologist. 2021 May;26(5):e863-e873. doi: 10.1002/onco.13629. Epub 2020 Dec 24.
citation: Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C, Healey JH, Chmielowski B, Staddon AP, Cohn AL, Shapiro GI, Keedy VL, Singh AS, Puzanov I, Kwak EL, Wagner AJ, Von Hoff DD, Weiss GJ, Ramanathan RK, Zhang J, Habets G, Zhang Y, Burton EA, Visor G, Sanftner L, Severson P, Nguyen H, Kim MJ, Marimuthu A, Tsang G, Shellooe R, Gee C, West BL, Hirth P, Nolop K, van de Rijn M, Hsu HH, Peterfy C, Lin PS, Tong-Starksen S, Bollag G. Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. N Engl J Med. 2015 Jul 30;373(5):428-37. doi: 10.1056/NEJMoa1411366.