Clinical trial NCT03069469: Study of Vimseltinib (DCC-3014) in Patients With Advanced Tumors and Tenosynovial Giant Cell Tumor
Official title: A Multicenter Phase 1/2, Open-Label Study of DCC-3014 to Assess the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics in Patients With Advanced Tumors and Tenosynovial Giant Cell Tumor
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Malignant Neoplasm
Pigmented Villonodular Synovitis
Giant Cell Tumor of Tendon Sheath
Tenosynovial Giant Cell Tumor
Tenosynovial Giant Cell Tumor, Diffuse
Keywords: TGCT
DTGCT
PVNS
Lead sponsor: Deciphera Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2017-03-03
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label Phase 1/2 study of vimseltinib in patients with malignant solid tumors and tenosynovial giant cell tumor (TGCT). There will be 2 distinct parts in this study: Dose Escalation (Phase 1) and Expansion (Phase 2). Phase 1 will enroll both malignant solid tumor and TGCT patients. Phase 2 will comprise two cohorts (Cohort A and Cohort B) and will only enroll TGCT patients.


Eligibility criteria: Inclusion Criteria

Dose Escalation Phase:

1. Patients ≥18 years of age
2. Patients must have:

   1. advanced malignant solid tumors; or
   2. symptomatic TGCT for which surgical resection is not an option (tumor biopsy to confirm diagnosis required if no histology/pathology available at screening)
3. Malignant solid tumor patients only: Able to provide a tumor tissue sample
4. Must have 1 measurable lesion according to RECIST Version 1.1
5. Malignant solid tumor patients only: Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
6. Adequate organ and bone marrow function
7. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
8. Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.

Expansion Phase (Cohorts A and B)

1. Patients ≥18 years of age
2. Patients must have symptomatic TGCT for which surgical resection is not an option (tumor biopsy to confirm diagnosis required if no histology/pathology available at screening)

   a) Expansion Cohort B: patients must have prior systemic treatment with anti-CSF1 or anti-CSF1R therapy, with the exception of imatinib or nilotinib
3. Adequate organ and bone marrow function
4. Must have at least 1 measurable lesion according to RECIST Version 1.1
5. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
6. Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.

Exclusion Criteria

Dose Escalation Phase:

1. Received anticancer therapy or therapy for TGCT, including investigational therapy, within 2 weeks or 28 days for therapies with half-life (t1/2) longer than 3 days prior to the administration of study drug.
2. Unresolved toxicity (Grade \>1 or baseline) from previous anticancer therapy or TGCT therapy, excluding alopecia.
3. Known active central nervous system (CNS) metastases.
4. History or presence of clinically relevant cardiovascular abnormalities.
5. Systemic arterial or venous thrombotic or embolic events.
6. QT interval corrected by Fridericia's formula (QTcF) \>450 ms in males or \>470 ms in females or history of long QT syndrome.
7. Left ventricular ejection fraction (LVEF) \<50%.
8. Concurrent treatment with proton-pump inhibitor(s).
9. Major surgery within 2 weeks of the first dose of study drug.
10. Malabsorption syndrome or other illness that could affect oral absorption.
11. Known human immunodeficiency virus, active hepatitis B, active hepatitis C, or active mycobacterium tuberculosis infection.
12. If female, the patient is pregnant or lactating.
13. Known allergy or hypersensitivity to any component of the study drug.
14. Any other clinically significant comorbidities.

Expansion Phase (Cohorts A and B)

1. Expansion Cohort A: received systemic therapy targeting CSF1 or CSF1R; previous therapy with imatinib and nilotinib is allowed.
2. Expansion Cohort B: discontinued systemic therapy targeting anti-CSF1 or anti-CSF1R due to drug-induced liver injury.
3. Treatment with therapy for TGCT, including investigational therapy, within 2 weeks or 28 days for therapies with a t1/2 longer than 3 days prior to the administration of the study drug.
4. Known metastatic TGCT or other active cancer that requires concurrent treatment.
5. QT interval corrected by Fridericia's formula (QTcF) \>450 ms in males or \>470 ms in females or history of long QT syndrome.
6. Left ventricular ejection fraction (LVEF) \<55%.
7. Concurrent treatment with proton-pump inhibitor(s).
8. Major surgery within 2 weeks of the first dose of study drug.
9. Any clinically significant comorbidities
10. Malabsorption syndrome or other illness that could affect oral absorption.
11. Known human immunodeficiency virus (HIV), active or chronic hepatitis B, active or chronic hepatitis C, or active mycobacterium tuberculosis infection.
12. If female, the patient is pregnant or lactating.
13. Known allergy or hypersensitivity to any component of the study drug.
14. Contraindication for MRI
15. Active liver or biliary disease, including evidence of fatty liver, nonalcoholic steatohepatitis (NASH), or cirrhosis

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Day 1 - Day 28 of Cycle 1 for each dose level tested
measure: Number of Patients with Dose-Limiting Toxicities (DLTs)
timeFrame: Day 1- Day 28 of Cycle 1 for each dose level tested
measure: Time to maximum observed concentration of Vimseltinib
timeFrame: Cycle 1 Day 1 and Day 8, and Cycle 2 Day 1 (pre-dose and at multiple time points (up to 8 hours) post-dose)
measure: Maximum observed concentration of Vimseltinib
timeFrame: Cycle 1 Day 1 and Day 8, and Cycle 2 Day 1 (pre-dose and at multiple time points (up to 8 hours) post-dose)
measure: Trough observed concentration of Vimseltinib
timeFrame: Cycle 1 Day 1 and Day 8, and Cycle 2 Day 1 (pre-dose and at multiple time points (up to 8 hours) post-dose)
measure: Area under the concentration-time curve (AUC) of Vimseltinib
timeFrame: Cycle 1 Day 1 and Day 8, and Cycle 2 Day 1 (pre-dose and at multiple time points (up to 8 hours) post-dose)
measure: Half life of Vimseltinib
timeFrame: Cycle 1 Day 1 and Day 8, and Cycle 2 Day 1 (pre-dose and at multiple time points (up to 8 hours) post-dose)
measure: Objective response rate (ORR= complete response [CR]+partial response [PR]) (Expansion Phase only)
timeFrame: At Week 25 (Cycle 7, Day 1)
measure: Duration of response rate (DOR) (Expansion Phase only)
timeFrame: Date from PR or CR to disease progression or death (Estimated up to 24 months)
Secondary outcomes:
measure: Response rate (Expansion Phase only)
timeFrame: At Week 25 (Cycle 7, Day 1)
measure: Range of Motion (ROM) (Expansion Phase only)
timeFrame: Baseline to Week 25 (Cycle 7, Day 1)
measure: Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) Score (Expansion Phase only)
timeFrame: Baseline to Week 25 (Cycle 7, Day 1)
measure: Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score (Expansion Phase only)
timeFrame: Baseline to Week 25 (Cycle 7, Day 1)
measure: Worst Stiffness Numeric Rating Scale (NRS) Score (Expansion Phase only)
timeFrame: Baseline to Week 25 (Cycle 7, Day 1)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Denver
country: United States
facility: University of Colorado - Denver
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Boston
country: United States
facility: Dana Farber
state: Massachusetts
city: New York
country: United States
facility: MSKCC
state: New York
city: Portland
country: United States
facility: OHSU
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
city: Lyon
country: France
facility: Centre Leon Berard
city: Paris
country: France
facility: Gustave Roussy Cancer Campus Grand Paris
city: Bologna
country: Italy
facility: IRCCS Istituto Ortopedico Rizzoli
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Dei Tumori
city: Milan
country: Italy
facility: Istituto Nazionale dei Tumori
city: Rome
country: Italy
facility: Regina Elena National Cancer Institute
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Warsaw
country: Poland
facility: M. Sklodowska-Curie Memorial Cancer Center
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío, Sevilla
city: London
country: United Kingdom
facility: University College Hospital
Study officials:
affiliation: Deciphera Pharmaceuticals, LLC
name: Maitreyi Sharma, MD
role: STUDY_DIRECTOR
References: