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

Sponsor
Deciphera Pharmaceuticals LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03069469
Collaborator
(none)
120
Enrollment
24
Locations
1
Arm
87.5
Anticipated Duration (Months)
5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 16, 2017
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

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.

Drug: DCC-3014
CSF1R inhibitor

Outcome Measures

Primary Outcome Measures

  1. Maximum tolerated dose [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

  2. Incidence of Adverse Events [Cycle 1 through study completion (~ 24 months)]

    Identify the observed adverse events, serious adverse events associated with DCC-3014

  3. Time to maximum observed concentration 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)]

    Measure the time to maximum plasma concentration of DCC-3014 in patients

  4. Maximum observed concentration 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)]

    Measure the maximum observed concentration of DCC-3014 in patients

  5. Trough observed concentration 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)]

    Measure the observed trough concentration of DCC-3014 in patients

  6. Area under the concentration-time curve 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)]

    Measure the AUC of DCC-3014

  7. Half life 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)]

    Measure half life of DCC-3014 in patients

  8. Objective response rate (ORR= complete response [CR]+partial response [PR]) (Expansion Phase only) [At Week 25 (Cycle 7, Day 1)]

    Assessed by central read using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1

  9. Duration of response rate (DOR) (Expansion Phase only) [Baseline through 24 months]

    Measure time from PR or CR to disease progression or death

Secondary Outcome Measures

  1. Response rate (Expansion Phase only) [At Week 25 (Cycle 7, Day 1)]

    Assessed by central read using tumor volume score and modified RECIST (mRECIST) Version 1.1

  2. Range of Motion (ROM) (Expansion Phase only) [Baseline to Week 25 (Cycle 7, Day 1)]

    Measure mean change from baseline in relative ROM

  3. Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) Score (Expansion Phase only) [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)

  4. Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score (Expansion Phase only) [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

  5. Worst Stiffness Numeric Rating Scale (NRS) Score (Expansion Phase only) [Baseline to Week 25 (Cycle 7, Day 1)]

    Analysis of patient reported outcomes based upon the Worst Stiffness Numeric Rating Scale (NRS)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Inclusion Criteria

Dose Escalation Phase:

  1. Patients ≥18 years of age

  2. Patients must have:

  3. advanced malignant solid tumors; or

  4. symptomatic TGCT for which surgical resection is not an option (tumor biopsy to confirm diagnosis required if no histology/pathology available at screening)

  5. Malignant solid tumor patients only: Able to provide a tumor tissue sample

  6. Must have 1 measurable lesion according to RECIST Version 1.1

  7. Malignant solid tumor patients only: Must have ECOG performance status of 0-1

  8. Adequate organ and bone marrow function

  9. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.

  10. 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)

  1. Expansion Cohort B: patients must have prior systemic treatment with anti-CSF1 or anti-CSF1R therapy, with the exception of imatinib or nilotinib

  1. Adequate organ and bone marrow function

  2. Must have at least 1 measurable lesion according to RECIST Version 1.1

  3. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.

  4. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Stanford Cancer Institute Palo Alto California United States 94304
2 University of Colorado - Denver Denver Colorado United States 80204
3 Mayo Clinic Jacksonville Florida United States 32224
4 University of Miami Miami Florida United States 33136
5 Dana Farber Boston Massachusetts United States 02215
6 MSKCC New York New York United States 10065
7 OHSU Portland Oregon United States 97239
8 Oregon Health & Science University Portland Oregon United States 97239
9 Sarah Cannon Research Institute Nashville Tennessee United States 37203
10 Peter MacCallum Cancer Centre Melbourne Australia
11 McGill University Health Centre Montréal Quebec Canada
12 Princess Margaret Cancer Center Toronto Canada
13 Centre Leon Berard Lyon France
14 Gustave Roussy Cancer Campus Grand Paris Paris France
15 IRCCS Istituto Ortopedico Rizzoli Bologna Italy
16 Fondazione IRCCS Istituto Nazionale Dei Tumori Milan Italy
17 Istituto Nazionale dei Tumori Milan Italy
18 Regina Elena National Cancer Institute Rome Italy
19 Leiden University Medical Center Leiden Netherlands
20 M. Sklodowska-Curie Memorial Cancer Center Warsaw Poland
21 Hospital Universitario Vall d'Hebron Barcelona Spain
22 Hospital Clinico San Carlos Madrid Spain
23 Hospital Universitario Virgen del Rocío, Sevilla Sevilla Spain
24 University College Hospital London United Kingdom

Sponsors and Collaborators

  • Deciphera Pharmaceuticals LLC

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Deciphera Pharmaceuticals LLC
ClinicalTrials.gov Identifier:
NCT03069469
Other Study ID Numbers:
  • DCC-3014-01-001
First Posted:
Mar 3, 2017
Last Update Posted:
Dec 22, 2021
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Deciphera Pharmaceuticals LLC
TGCT
DTGCT
PVNS
Additional relevant MeSH terms:
Neoplasms
Giant Cell Tumors
Giant Cell Tumor of Tendon Sheath
Synovitis, Pigmented Villonodular
Synovitis

Study Results

No Results Posted as of Dec 22, 2021