We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of DCC-3014 in Patients With Advanced Malignancies

This study is currently recruiting participants.
Verified May 2017 by Deciphera Pharmaceuticals LLC
Sponsor:
ClinicalTrials.gov Identifier:
NCT03069469
First Posted: March 3, 2017
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Deciphera Pharmaceuticals LLC
  Purpose
This is a multicenter, open-label Phase 1 study of DCC-3014 in patients with advanced malignancies, featuring solid tumors, but will also enroll select patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), acute lymphocytic leukemia (ALL), or chronic lymphocytic leukemia (CLL). There will be an Escalation Phase and an Expansion Phase in this study

Condition Intervention Phase
Advanced Malignant Neoplasm Drug: DCC-3014 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multi-center, Phase 1, Open-Label Study of DCC-3014 to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Patients With Advanced Malignancies

Further study details as provided by Deciphera Pharmaceuticals LLC:

Primary Outcome Measures:
  • 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

  • Incidence of Adverse Events [ Time Frame: Day -7 pre-Cycle 1 through study completion (~ 18 months) ]
    Identify the observed adverse events, serious adverse events associated with DCC-3014

  • Time to observed concentration of DCC-3014 [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 2 through study completion (~18 months) at the following time points: 0.5, 1, 2, 4, 6, 8, 10, 24 hours post-dose ]
    Measure the concentration of DCC-3014 in patients

  • Maximum observed concentration of DCC-3014 [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 2 through study completion (~ 18 months) at the following time points: 0.5, 1, 2, 4, 6, 8, 10, 24 hours post-dose ]
    Measure the observed concentration of DCC-3014 in patients

  • Trough observed concentration of DCC-3014 [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 2 through study completion (~18 months) at the following time points: 0.5, 1, 2, 4, 6, 8, 10, 24 hours post-dose ]
    Measure the concentration of DCC-3014 in patients

  • Area under the concentration-time curve of DCC-3014 [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 2 through study completion (~18 months) at the following time points: 0.5, 1, 2, 4, 6, 8, 10, 24 hours post-dose ]
    Measure the AUC of DCC-3014

  • Half life of DCC-3014 [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 2 through study completion (~18 months) at the following time points: 0.5, 1, 2, 4, 6, 8, 10, 24 hours post-dose ]
    Measure the half life of DCC-3014 in patients


Secondary Outcome Measures:
  • Levels of CSF1R-dependent myeloid cells [ Time Frame: Day 0 Cycle 1 through study completion (~18 months) ]
    Measure the amount of CSF1R-dependent myeloid cells in patients


Estimated Enrollment: 55
Actual Study Start Date: February 16, 2017
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental Treatment

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 escalation phase of the study.

Drug: DCC-3014
CSF1R inhibitor

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (Solid Tumor Patients):

  1. Patients ≥18 years of age,
  2. Must have progressed on all available therapies known to confer benefit for disease
  3. Must have tissue source of tumor cells
  4. Must have 1 measurable lesion according to RECIST Version 1.1
  5. Must have objective evidence of progression of lesions that have been previously irradiated
  6. Must have ECOG performance status of 0-1
  7. Bone Marrow Function: absolute neutrophil count (ANC) ≥1500/µL; hemoglobin ≥9 g/dL; platelet count ≥75,000/µL
  8. Hepatic Function: Total serum bilirubin ≤1.5 times the upper limit of normal (ULN; except for patients with known Gilbert syndrome);); serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT), ≤32.5×ULN (≤5×ULN in the presence of hepatic metastases)
  9. Renal Function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min based either on urine collection or Cockcroft-Gault estimation
  10. Coagulation Profile: Prothrombin time (PT) - international normalized ratio (INR)/partial thromboplastin time (PTT) ≤1.5xULN5×ULN.

Inclusion Criteria (Hematologic Malignancies):

  1. Patients ≥18 years of age, except for patients with ALL who can be ≥16 years of age
  2. Morphologically documented relapsed/refractory myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL) as defined by World Health Organization (WHO) criteria
  3. Patients with relapsed/refractory MDS, AML, ALL must have progressed on least 1 prior therapy and cannot be a candidate for any available therapies in patients with a rationale for known to confer clinical benefit
  4. For patients with MDS, AML, ALL, or CLL, must have cells obtained either by bone marrow biopsy or blood collection to use for biomarkers that may enrich for DCC-3014 response or provide PD information
  5. For CLL, must have measurable disease per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria (Hallek criteria) to allow evaluation of response
  6. May have primary phagocytic malignancies including histocytoses, including Erdheim Chester Disease (as diagnosed in Diamond et al 2014) and Langerhans histiocytoses are eligible if refractory to or unsuitable for other therapies.
  7. ECOG PS of 0-2
  8. Bone Marrow Function: ANC ≥1000/µL; hemoglobin ≥8 g/dL; platelet count ≥75,000/μL.
  9. Hepatic Function: Total serum bilirubin <1.5×ULN; serum AST and ALT <2.5×ULN (≤5×ULN in the presence of hepatic metastases).
  10. Renal Function: Serum creatinine <2xULN1.5×ULN, or glomerular filtration rate >2050 mL/hr as calculated by CockgroftCockroft-Gault formula.
  11. Serum potassium, magnesium and calcium (corrected for albumin) that are within institutional normal limits or can be corrected with supplementation.
  12. Total serum bilirubin <2xULN (except for patients with known Gilbert syndrome).
  13. Serum AST and ALT <5xULN.
  14. Coagulation Profile: Prothrombin time (PT) - international normalized ratio (INR)/partial thromboplastin time (PTT) ≤1.5×ULN.

Exclusion Criteria (Solid Tumors):

  1. Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to the administration of study drug. For immediately prior therapies with a half-life longer than 3 days, or if the half-life is not available, the interval must be ≥28 days prior to the first administration of study drug.
  2. Unresolved toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 (ie, >Grade 1 or baseline) from previous anticancer therapy, excluding alopecia.
  3. The patient has known active CNS metastases. Patients with previously treated brain metastases may participate provided that:

    • They are stable (ie, without evidence of progression by magnetic resonance imaging [MRI]) for ≥4 weeks prior to the first dose of study drug),
    • All neurologic symptoms have returned to baseline, and
    • Patients do not require continued steroid therapy or use of enzyme-inducing antiepileptic drugs. Patients can be switched to a non-enzyme inducing antiepileptic drug. If signs or symptoms suggest CNS metastases, a brain MRI must be performed to confirm absence of detectable CNS disease within 2 weeks prior to receiving study drug.
  4. New York Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure.
  5. Systemic arterial thrombotic or embolic events, such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months prior to the start of study drug.
  6. Systemic venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) within the 1 month prior to the start of study drug. Patients with venous thrombotic events before the start of study drug on stable anticoagulation therapy are eligible.
  7. Baseline prolongation of the rate-corrected QT interval based on repeated demonstration of QT interval corrected (QTc) >450 ms or history of long QTc syndrome.
  8. Left ventricular ejection fraction (LVEF) <50%.
  9. Concurrent treatment with proton-pump inhibitor. Other medications that increase gastric pH, ie, histamine H2 receptor antagonists and antacids may be taken provided they are not administered within 2 hours before or after administration of study drug.
  10. Major surgery within 2 weeks of the first dose of study drug; following major surgeries >2 weeks prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence.
  11. Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks.
  12. Malabsorption syndrome or other illness that could affect oral absorption.
  13. Known human immunodeficiency virus, active hepatitis B, active hepatitis C, or active mycobacterium tuberculosis infection.
  14. If female, the patient is pregnant or lactating.
  15. Known allergy or hypersensitivity to any component of the study drug.
  16. Patients with known Gilbert's disease.

Exclusion Criteria (Hematologic Malignancies):

  1. Concurrent active malignancy with expected survival of less than 1 year.
  2. Graft versus host disease (GVHD) that is not well-controlled on a stable treatment regimen for at least 3 weeks prior to initial dose of study drug.
  3. Cancer-directed therapy within 2 weeks prior to starting treatment, with the exception of hydroxyurea, which is allowed to control white blood cell count.
  4. History of, or current, central nervous system involvement with MDS, AML, or CLL.
  5. Systemic arterial thrombotic or embolic events, such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 2 months prior to the start of study drug.
  6. Systemic venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) within the 1 month prior to the start of study drug. Patients with venous thrombotic events before the start of study drug on stable anticoagulation therapy are eligible.
  7. Clinically significant coagulation disorder, such as disseminated intravascular coagulation.
  8. New York Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure.
  9. Baseline prolongation of the rate-corrected QT interval based on repeated demonstration of QTc >450 ms or history of long QTc syndrome.
  10. LVEF <50%.
  11. Concurrent treatment with proton-pump inhibitor.
  12. Major surgery within 2 weeks of the first dose of study drug; following major surgeries >2 weeks prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence.
  13. Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks.
  14. Malabsorption syndrome or other illness that could affect oral absorption.
  15. Known human immunodeficiency virus, active hepatitis B, active hepatitis C, active cytomegalovirus (CMV), or active mycobacterium tuberculosis infection.
  16. Active infection that is not well-controlled by antibacterial or antiviral therapy.
  17. If female, the patient is pregnant or lactating.
  18. Known allergy or hypersensitivity to any component of the study drug.
  19. Diagnosis of acute promyelocytic leukemia (APL, or AML M3 subtype).
  20. Unwillingness to receive infusion of blood products.
  21. Patients with known Gilbert's disease.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03069469


Contacts
Contact: Jama Pitman 785-830-2100 jpitman@deciphera.com

Locations
United States, Colorado
University of Colorado - Denver Recruiting
Denver, Colorado, United States, 80204
Contact: Stephen Leong, MD         
United States, Oregon
OHSU Recruiting
Portland, Oregon, United States, 97239
Contact: Matthew Taylor, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Todd Bauer, MD         
Principal Investigator: Todd Bauer, MD         
Sponsors and Collaborators
Deciphera Pharmaceuticals LLC
Investigators
Study Director: Oliver Rosen, MD Deciphera Pharmaceuticals LLC
  More Information

Responsible Party: Deciphera Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT03069469     History of Changes
Other Study ID Numbers: DCC-3014-01-001
First Submitted: February 20, 2017
First Posted: March 3, 2017
Last Update Posted: May 30, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
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:
CSF1R
ALL
CML
AML
MDS

Additional relevant MeSH terms:
Neoplasms