Study of Vimseltinib (DCC-3014) in Patients With Advanced Tumors and Tenosynovial Giant Cell Tumor

Advanced Malignant Neoplasm Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03069469
• Other study ID #: DCC-3014-01-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 16, 2017
• Est. completion date: August 2028

Study information

• Verified date: May 2024
• Source: Deciphera Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: August 2028
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Malignant Neoplasm
• Giant Cell Tumor of Tendon Sheath
• Giant Cell Tumors
• Neoplasms
• Pigmented Villonodular Synovitis
• Synovitis
• Synovitis, Pigmented Villonodular
• Tenosynovial Giant Cell Tumor
• Tenosynovial Giant Cell Tumor, Diffuse

Intervention

Drug:
• Vimseltinib
Colony-stimulating factor 1 receptor (CSF1R) inhibitor

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Princess Margaret Cancer Center	Toronto
France	Centre Leon Berard	Lyon
France	Gustave Roussy Cancer Campus Grand Paris	Paris
Italy	IRCCS Istituto Ortopedico Rizzoli	Bologna
Italy	Fondazione IRCCS Istituto Nazionale Dei Tumori	Milan
Italy	Istituto Nazionale dei Tumori	Milan
Italy	Regina Elena National Cancer Institute	Rome
Netherlands	Leiden University Medical Center	Leiden
Poland	M. Sklodowska-Curie Memorial Cancer Center	Warsaw
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario Virgen del Rocío, Sevilla	Sevilla
United Kingdom	University College Hospital	London
United States	Dana Farber	Boston	Massachusetts
United States	University of Colorado - Denver	Denver	Colorado
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Miami	Miami	Florida
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	MSKCC	New York	New York
United States	Stanford Cancer Institute	Palo Alto	California
United States	OHSU	Portland	Oregon
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Deciphera Pharmaceuticals LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	Determine the maximum tolerated dose.	Day 1 - Day 28 of Cycle 1 for each dose level tested
Primary	Number of Patients with Dose-Limiting Toxicities (DLTs)	Identify the number of patients with DLTs for each dose level tested.	Day 1- Day 28 of Cycle 1 for each dose level tested
Primary	Time to maximum observed concentration of Vimseltinib	Measure the time to maximum plasma concentration of vimseltinib in patients.	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)
Primary	Maximum observed concentration of Vimseltinib	Measure the maximum observed concentration of vimseltinib in patients.	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)
Primary	Trough observed concentration of Vimseltinib	Measure the observed trough concentration of vimseltinib in patients.	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)
Primary	Area under the concentration-time curve (AUC) of Vimseltinib	Measure the AUC of vimseltinib.	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)
Primary	Half life of Vimseltinib	Measure half life of vimseltinib in patients.	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)
Primary	Objective response rate (ORR= complete response [CR]+partial response [PR]) (Expansion Phase only)	Assessed by central read using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.	At Week 25 (Cycle 7, Day 1)
Primary	Duration of response rate (DOR) (Expansion Phase only)	Measure time from partial response (PR) or complete response (CR) to disease progression or death.	Date from PR or CR to disease progression or death (Estimated up to 24 months)
Secondary	Response rate (Expansion Phase only)	Assessed by central read using tumor volume score and modified RECIST (mRECIST) Version 1.1	At Week 25 (Cycle 7, Day 1)
Secondary	Range of Motion (ROM) (Expansion Phase only)	Measure mean change from baseline in relative ROM	Baseline to Week 25 (Cycle 7, Day 1)
Secondary	Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) Score (Expansion Phase only)	Proportion of responders based on Brief Pain Inventory (BPI) worst pain numeric rating scale (NRS) and narcotic analgesic use by Brief Pain Inventory-30 (BPI-30)	Baseline to Week 25 (Cycle 7, Day 1)
Secondary	Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score (Expansion Phase only)	Analysis of patient reported outcomes based upon the patient-reported outcomes measurement information system (PROMIS) physical function questionnaire	Baseline to Week 25 (Cycle 7, Day 1)
Secondary	Worst Stiffness Numeric Rating Scale (NRS) Score (Expansion Phase only)	Analysis of patient reported outcomes based upon the Worst Stiffness Numeric Rating Scale (NRS)	Baseline to Week 25 (Cycle 7, Day 1)