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

Primary Purpose

Advanced Malignant Neoplasm, Pigmented Villonodular Synovitis, Giant Cell Tumor of Tendon Sheath

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DCC-3014
Sponsored by
Deciphera Pharmaceuticals LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Malignant Neoplasm focused on measuring TGCT, DTGCT, PVNS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford Cancer Institute
  • University of Colorado - Denver
  • Mayo Clinic
  • University of Miami
  • Dana Farber
  • MSKCC
  • OHSU
  • Oregon Health & Science University
  • Sarah Cannon Research Institute
  • Peter MacCallum Cancer Centre
  • McGill University Health Centre
  • Princess Margaret Cancer Center
  • Centre Leon Berard
  • Gustave Roussy Cancer Campus Grand Paris
  • IRCCS Istituto Ortopedico Rizzoli
  • Fondazione IRCCS Istituto Nazionale Dei Tumori
  • Istituto Nazionale dei Tumori
  • Regina Elena National Cancer Institute
  • Leiden University Medical Center
  • M. Sklodowska-Curie Memorial Cancer Center
  • Hospital Universitario Vall d'Hebron
  • Hospital Clinico San Carlos
  • Hospital Universitario Virgen del Rocío, Sevilla
  • University College Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Experimental Treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum tolerated dose
Identify the dose limiting toxicities for each dose level tested and determine the maximum tolerated dose and recommended Phase 2 dose
Incidence of Adverse Events
Identify the observed adverse events, serious adverse events associated with DCC-3014
Time to maximum observed concentration of DCC-3014
Measure the time to maximum plasma concentration of DCC-3014 in patients
Maximum observed concentration of DCC-3014
Measure the maximum observed concentration of DCC-3014 in patients
Trough observed concentration of DCC-3014
Measure the observed trough concentration of DCC-3014 in patients
Area under the concentration-time curve of DCC-3014
Measure the AUC of DCC-3014
Half life of DCC-3014
Measure half life of DCC-3014 in patients
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
Duration of response rate (DOR) (Expansion Phase only)
Measure time from PR or CR to disease progression or death

Secondary Outcome Measures

Response rate (Expansion Phase only)
Assessed by central read using tumor volume score and modified RECIST (mRECIST) Version 1.1
Range of Motion (ROM) (Expansion Phase only)
Measure mean change from baseline in relative ROM
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)
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
Worst Stiffness Numeric Rating Scale (NRS) Score (Expansion Phase only)
Analysis of patient reported outcomes based upon the Worst Stiffness Numeric Rating Scale (NRS)

Full Information

First Posted
February 20, 2017
Last Updated
October 5, 2023
Sponsor
Deciphera Pharmaceuticals LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03069469
Brief Title
Study of 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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 16, 2017 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Deciphera Pharmaceuticals LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental Treatment
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
DCC-3014
Intervention Description
CSF1R inhibitor
Primary Outcome Measure Information:
Title
Maximum tolerated dose
Description
Identify the dose limiting toxicities for each dose level tested and determine the maximum tolerated dose and recommended Phase 2 dose
Time Frame
Day 1 - Day 28 of Cycle 1 for each dose level tested
Title
Incidence of Adverse Events
Description
Identify the observed adverse events, serious adverse events associated with DCC-3014
Time Frame
Cycle 1 through study completion (~ 24 months)
Title
Time to maximum observed concentration of DCC-3014
Description
Measure the time to maximum plasma concentration of DCC-3014 in patients
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)
Title
Maximum observed concentration of DCC-3014
Description
Measure the maximum observed concentration of DCC-3014 in patients
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)
Title
Trough observed concentration of DCC-3014
Description
Measure the observed trough concentration of DCC-3014 in patients
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)
Title
Area under the concentration-time curve of DCC-3014
Description
Measure the AUC 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)
Title
Half life of DCC-3014
Description
Measure half life of DCC-3014 in patients
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)
Title
Objective response rate (ORR= complete response [CR]+partial response [PR]) (Expansion Phase only)
Description
Assessed by central read using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Time Frame
At Week 25 (Cycle 7, Day 1)
Title
Duration of response rate (DOR) (Expansion Phase only)
Description
Measure time from PR or CR to disease progression or death
Time Frame
Baseline through 24 months
Secondary Outcome Measure Information:
Title
Response rate (Expansion Phase only)
Description
Assessed by central read using tumor volume score and modified RECIST (mRECIST) Version 1.1
Time Frame
At Week 25 (Cycle 7, Day 1)
Title
Range of Motion (ROM) (Expansion Phase only)
Description
Measure mean change from baseline in relative ROM
Time Frame
Baseline to Week 25 (Cycle 7, Day 1)
Title
Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) Score (Expansion Phase only)
Description
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)
Time Frame
Baseline to Week 25 (Cycle 7, Day 1)
Title
Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score (Expansion Phase only)
Description
Analysis of patient reported outcomes based upon the patient-reported outcomes measurement information system (PROMIS) physical function questionnaire
Time Frame
Baseline to Week 25 (Cycle 7, Day 1)
Title
Worst Stiffness Numeric Rating Scale (NRS) Score (Expansion Phase only)
Description
Analysis of patient reported outcomes based upon the Worst Stiffness Numeric Rating Scale (NRS)
Time Frame
Baseline to Week 25 (Cycle 7, Day 1)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Dose Escalation Phase: Patients ≥18 years of age Patients must have: advanced malignant solid tumors; or symptomatic TGCT for which surgical resection is not an option (tumor biopsy to confirm diagnosis required if no histology/pathology available at screening) Malignant solid tumor patients only: Able to provide a tumor tissue sample Must have 1 measurable lesion according to RECIST Version 1.1 Malignant solid tumor patients only: Must have ECOG performance status of 0-1 Adequate organ and bone marrow function If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements. Must provide signed consent to participate in the study and is willing to comply with study-specific procedures. Expansion Phase (Cohorts A and B) Patients ≥18 years of age 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 Adequate organ and bone marrow function Must have at least 1 measurable lesion according to RECIST Version 1.1 If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements. Must provide signed consent to participate in the study and is willing to comply with study-specific procedures. Exclusion Criteria Dose Escalation Phase: 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. Unresolved toxicity (Grade >1 or baseline) from previous anticancer therapy or TGCT therapy, excluding alopecia. Known active CNS metastases. History or presence of clinically relevant cardiovascular abnormalities. Systemic arterial or venous thrombotic or embolic events. QT interval corrected by Fridericia's formula (QTcF) >450 ms in males or >470 ms in females or history of long QT syndrome. Left ventricular ejection fraction (LVEF) <50%. Concurrent treatment with proton-pump inhibitor(s). Major surgery within 2 weeks of the first dose of study drug. Malabsorption syndrome or other illness that could affect oral absorption. Known human immunodeficiency virus, active hepatitis B, active hepatitis C, or active mycobacterium tuberculosis infection. If female, the patient is pregnant or lactating. Known allergy or hypersensitivity to any component of the study drug. Any other clinically significant comorbidities. Expansion Phase (Cohorts A and B) Expansion Cohort A: received systemic therapy targeting CSF1 or CSF1R; previous therapy with imatinib and nilotinib is allowed. Expansion Cohort B: discontinued systemic therapy targeting anti-CSF1 or anti-CSF1R due to drug-induced liver injury. 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. Known metastatic TGCT or other active cancer that requires concurrent treatment. QT interval corrected by Fridericia's formula (QTcF) >450 ms in males or >470 ms in females or history of long QT syndrome. Left ventricular ejection fraction (LVEF) <55%. Concurrent treatment with proton-pump inhibitor(s). Major surgery within 2 weeks of the first dose of study drug. Any clinically significant comorbidities Malabsorption syndrome or other illness that could affect oral absorption. Known human immunodeficiency virus (HIV), active or chronic hepatitis B, active or chronic hepatitis C, or active mycobacterium tuberculosis infection. If female, the patient is pregnant or lactating. Known allergy or hypersensitivity to any component of the study drug. Contraindication for MRI Active liver or biliary disease, including evidence of fatty liver, nonalcoholic steatohepatitis (NASH), or cirrhosis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maitreyi Sharma, MD
Organizational Affiliation
Deciphera Pharmaceuticals LLC
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Cancer Institute
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of Colorado - Denver
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Dana Farber
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
MSKCC
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
OHSU
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
Country
Australia
Facility Name
McGill University Health Centre
City
Montréal
State/Province
Quebec
Country
Canada
Facility Name
Princess Margaret Cancer Center
City
Toronto
Country
Canada
Facility Name
Centre Leon Berard
City
Lyon
Country
France
Facility Name
Gustave Roussy Cancer Campus Grand Paris
City
Paris
Country
France
Facility Name
IRCCS Istituto Ortopedico Rizzoli
City
Bologna
Country
Italy
Facility Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
City
Milan
Country
Italy
Facility Name
Istituto Nazionale dei Tumori
City
Milan
Country
Italy
Facility Name
Regina Elena National Cancer Institute
City
Rome
Country
Italy
Facility Name
Leiden University Medical Center
City
Leiden
Country
Netherlands
Facility Name
M. Sklodowska-Curie Memorial Cancer Center
City
Warsaw
Country
Poland
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Clinico San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocío, Sevilla
City
Sevilla
Country
Spain
Facility Name
University College Hospital
City
London
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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

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