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

October 5, 2023 updated by: Deciphera Pharmaceuticals LLC

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

This is a multicenter, open-label Phase 1/2 study of DCC-3014 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.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Melbourne, Australia
        • Peter MacCallum Cancer Centre
      • Toronto, Canada
        • Princess Margaret Cancer Center
    • Quebec
      • Montréal, Quebec, Canada
        • McGill University Health Centre
      • Lyon, France
        • Centre Leon Berard
      • Paris, France
        • Gustave Roussy Cancer Campus Grand Paris
      • Bologna, Italy
        • IRCCS istituto Ortopedico Rizzoli
      • Milan, Italy
        • Istituto Nazionale dei Tumori
      • Milan, Italy
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Rome, Italy
        • Regina Elena National Cancer Institute
      • Leiden, Netherlands
        • Leiden University Medical Center
      • Warsaw, Poland
        • M. Sklodowska-Curie Memorial Cancer Center
      • Barcelona, Spain
        • Hospital Universitario Vall d'Hebron
      • Madrid, Spain
        • Hospital Clinico San Carlos
      • Sevilla, Spain
        • Hospital Universitario Virgen del Rocío, Sevilla
      • London, United Kingdom
        • University College Hospital
    • California
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Institute
    • Colorado
      • Denver, Colorado, United States, 80204
        • University of Colorado - Denver
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
      • Miami, Florida, United States, 33136
        • University of Miami
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber
    • New York
      • New York, New York, United States, 10065
        • MSKCC
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
      • Portland, Oregon, United States, 97239
        • OHSU
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Experimental Treatment

Dose Escalation Phase: Increasing doses of DCC-3014 beginning at 10 mg QD for 28 day cycles until disease progression or unacceptable toxicity.

Expansion Phase: Dosing of different patient cohorts at the dose level determined from the Dose Escalation Phase of the study.

CSF1R inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose
Time Frame: Day 1 - Day 28 of Cycle 1 for each dose level tested
Identify the dose limiting toxicities for each dose level tested and determine the maximum tolerated dose and recommended Phase 2 dose
Day 1 - Day 28 of Cycle 1 for each dose level tested
Incidence of Adverse Events
Time Frame: Cycle 1 through study completion (~ 24 months)
Identify the observed adverse events, serious adverse events associated with DCC-3014
Cycle 1 through study completion (~ 24 months)
Time to maximum observed concentration of DCC-3014
Time Frame: 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 the time to maximum plasma concentration of DCC-3014 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)
Maximum observed concentration of DCC-3014
Time Frame: 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 the maximum observed concentration of DCC-3014 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)
Trough observed concentration of DCC-3014
Time Frame: 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 the observed trough concentration of DCC-3014 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)
Area under the concentration-time curve of DCC-3014
Time Frame: 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 the AUC of DCC-3014
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)
Half life of DCC-3014
Time Frame: 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 DCC-3014 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)
Objective response rate (ORR= complete response [CR]+partial response [PR]) (Expansion Phase only)
Time Frame: At Week 25 (Cycle 7, Day 1)
Assessed by central read using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
At Week 25 (Cycle 7, Day 1)
Duration of response rate (DOR) (Expansion Phase only)
Time Frame: Baseline through 24 months
Measure time from PR or CR to disease progression or death
Baseline through 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate (Expansion Phase only)
Time Frame: At Week 25 (Cycle 7, Day 1)
Assessed by central read using tumor volume score and modified RECIST (mRECIST) Version 1.1
At Week 25 (Cycle 7, Day 1)
Range of Motion (ROM) (Expansion Phase only)
Time Frame: Baseline to Week 25 (Cycle 7, Day 1)
Measure mean change from baseline in relative ROM
Baseline to Week 25 (Cycle 7, Day 1)
Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) Score (Expansion Phase only)
Time Frame: Baseline to Week 25 (Cycle 7, Day 1)
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)
Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score (Expansion Phase only)
Time Frame: Baseline to Week 25 (Cycle 7, Day 1)
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)
Worst Stiffness Numeric Rating Scale (NRS) Score (Expansion Phase only)
Time Frame: Baseline to Week 25 (Cycle 7, Day 1)
Analysis of patient reported outcomes based upon the Worst Stiffness Numeric Rating Scale (NRS)
Baseline to Week 25 (Cycle 7, Day 1)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Maitreyi Sharma, MD, Deciphera Pharmaceuticals LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 16, 2017

Primary Completion (Estimated)

December 1, 2023

Study Completion (Estimated)

June 1, 2024

Study Registration Dates

First Submitted

February 20, 2017

First Submitted That Met QC Criteria

February 27, 2017

First Posted (Actual)

March 3, 2017

Study Record Updates

Last Update Posted (Actual)

October 6, 2023

Last Update Submitted That Met QC Criteria

October 5, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Advanced Malignant Neoplasm

Clinical Trials on DCC-3014

Subscribe