Safety Study of PLX108-01 in Patients With Solid Tumors - Full Text View

Purpose

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.

Condition	Intervention	Phase
At This Time, All Cohorts Are Closed to Enrollment With the Exception of the Pigmented Villo-nodular Synovitis (PVNS) Cohort.	Drug: PLX3397	Phase 1


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Synovitis Pigmented Villonodular Synovitis

U.S. FDA Resources

Further study details as provided by Plexxikon:

Primary Outcome Measures:

Safety: subject incidence of adverse events, first-cycle DLTs and clinically significant changes in vital signs, ECGs and clinical laboratory tests [ Time Frame: till end of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

PK profile: PLX3397 PK parameters including, but not limited to, maximum observed concentration (Cmax), area under the plasma concentration-time curve and half-life [ Time Frame: till end of study ] [ Designated as safety issue: No ]


Estimated Enrollment:	150
Study Start Date:	September 2009
Estimated Study Completion Date:	September 2017
Estimated Primary Completion Date:	June 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: PLX3397	Drug: PLX3397 Capsules administered once or twice daily, continuous dosing

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.
ECOG 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 QTc >= 450 msec (for males) or QTc >= 470 msec (for females)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01004861

Locations


United States, Arizona
TGen Clinical Research Service at Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
United States, California
UCLA
Los Angeles, California, United States, 90404
United States, Colorado
Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80218
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, New York
Memorial Sloan-Kettering Cancer Center (MSKCC)
New York, New York, United States, 10065
United States, Pennsylvania
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Vanderbilt-Ingram Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Texas Oncology, PA (North)
Dallas, Texas, United States, 75246
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
United States, Washington
Evergreen Hematology & Oncology
Spokane, Washington, United States, 99218

Sponsors and Collaborators

Plexxikon

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


Responsible Party:	Plexxikon
ClinicalTrials.gov Identifier:	NCT01004861 History of Changes
Other Study ID Numbers:	PLX108-01
Study First Received:	October 28, 2009
Last Updated:	August 8, 2016
Health Authority:	United States: Food and Drug Administration

Keywords provided by Plexxikon:


PVNS

Additional relevant MeSH terms:


Synovitis Synovitis, Pigmented Villonodular Joint Diseases Musculoskeletal Diseases

ClinicalTrials.gov processed this record on September 27, 2016