Clinical Trials /

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

NCT03069469

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Tenosynovial Giant Cell Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: DCC-3014-01-001
  • NCT ID: NCT03069469

Conditions

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

Interventions

DrugSynonymsArms
DCC-3014Experimental Treatment

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Experimental TreatmentOtherDose 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.
  • DCC-3014

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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose
Time Frame:Day 1 - Day 28 of Cycle 1 for each dose level tested
Safety Issue:
Description:Identify the dose limiting toxicities for each dose level tested and determine the maximum tolerated dose and recommended Phase 2 dose

Secondary Outcome Measures

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Deciphera Pharmaceuticals LLC

Trial Keywords

  • TGCT
  • DTGCT
  • PVNS

Last Updated

April 1, 2021