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Trial record 1 of 1 for:    NCT02571036
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A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by Deciphera Pharmaceuticals LLC
Sponsor:
Information provided by (Responsible Party):
Deciphera Pharmaceuticals LLC
ClinicalTrials.gov Identifier:
NCT02571036
First received: October 5, 2015
Last updated: August 4, 2017
Last verified: July 2017
  Purpose
This is a Phase 1, open-label, first-in-human (FIH) dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary antitumor activity of DCC-2618, administered orally (PO), in adult patients with advanced malignancies. The study consists of 2 parts, a dose-escalation phase and an expansion phase.

Condition Intervention Phase
Gastrointestinal Stromal Tumors Aggressive Systemic Mastocytosis Advanced Cancers Drug: DCC-2618 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Phase 1, Open-Label Study of DCC-2618 to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by Deciphera Pharmaceuticals LLC:

Primary Outcome Measures:
  • Dose limiting toxicities, AEs, SAEs, discontinuation of drug due to toxicity, physical exams and ECOG PS, ophthalmologic examinations, changes from baseline in laboratory parameters, electrocardiograms, LVEF, and vital signs. [ Time Frame: Approximately 24 months ]
    Dose limiting toxicities, AEs, SAEs, discontinuation of drug due to toxicity, physical exams and ECOG PS, ophthalmologic examinations, changes from baseline in laboratory parameters, electrocardiograms, LVEF, and vital signs.

  • Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose [ Time Frame: 18 months ]

Secondary Outcome Measures:
  • Maximum plasma concentration of DCC-2618 (Tmax) [ Time Frame: Predose and up to 24 hours postdose (Cycle = 28 Days) ]
  • Maximum observed plasma concentration of DCC-2618 (Cmax) [ Time Frame: Predose and up to 24 hours postdose (Cycle = 28 Days) ]
  • Concentration of DCC-2618 in blood plasma against time [area under the concentration-time curve (AUC)] [ Time Frame: Predose and up to 24 hours postdose (Cycle = 28 Days) ]
  • Period of time required for the concentration/amount of DCC-2618 in the body to be reduced by one-half [ Time Frame: Predose and up to 24 hours postdose (Cycle = 28 Days) ]
  • Objective response rate (complete response [CR] + partial response [PR]); [ Time Frame: 12 weeks ]
  • Preliminary evidence of antitumor activity by disease control rate (complete response [CR] + partial response [PR] + stable disease [SD]) [ Time Frame: 12 weeks ]
  • Plasma concentration levels with food interactions [ Time Frame: Day -7 during the escalation phase only ]
  • Time to best objective response by modified RECIST 1.1 [ Time Frame: From C1D1 to PR or CR up to 1 year ]
  • Progression free survival [ Time Frame: C1D1 to PR or CR up to 1 year ]
  • Decrease in mast cell burden using IWG-MRT and ECNM consensus response criteria for patients with SM [ Time Frame: C2D1 and every cycle thereafter up to 1 year ]
  • Changes in serum tryptase levels for patients with SM [ Time Frame: C1D1, C1D8, C1D15, C2D1 and then every day 1 of new cycle up to 1 year ]
  • Overall Response by RANO Criteria (glioma patients) [ Time Frame: 12 weeks ]
  • Changes in patient reported outcome measurements using NCI-PRO-CTCAE [ Time Frame: Every planned study visit until study completion up to 1 year ]

Estimated Enrollment: 250
Study Start Date: October 2015
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Escalation
Escalation Phase: DCC-2618 tablets in escalating dose cohorts given orally BID (twice daily) every 12 hours or once daily (QD) for repeated 28-day cycles. Participants may continue to receive study drug until discontinuation criteria are met.
Drug: DCC-2618
10 mg and 50 mg formulated tablets
Experimental: Expansion Cohort 1
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received 3 prior therapies.
Drug: DCC-2618
10 mg and 50 mg formulated tablets
Experimental: Expansion Cohort 2
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received 4 prior therapies.
Drug: DCC-2618
10 mg and 50 mg formulated tablets
Experimental: Expansion Cohort 3
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received at least one prior therapies not no more that 2 prior therapies.
Drug: DCC-2618
10 mg and 50 mg formulated tablets
Experimental: Expansion Cohort 4
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with Systemic Mastocytosis and other hematologic malignancies.
Drug: DCC-2618
10 mg and 50 mg formulated tablets
Experimental: Expansion Cohort 5
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with malignant gliomas.
Drug: DCC-2618
10 mg and 50 mg formulated tablets
Experimental: Expansion Cohort 6
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with other solid tumors.
Drug: DCC-2618
10 mg and 50 mg formulated tablets

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients must meet all of the following criteria to be eligible to enroll in the study:

  1. Patients must have histologically confirmed solid tumors or hematologic malignancies with a locally advanced malignancy refractory to standard therapies, no alternative effective therapy available, and/or be intolerant to standard therapies. Eligible patients include the following:

    1. GIST patients must have a KIT and PDGFRA mutation and must have progressed on or had an intolerability to at least 1 but not more than 4 lines of systemic anticancer therapy
    2. Systemic mastocytosis (SM) patients must have a confirmed diagnosis of advanced SM according to 2016 World Health Organization (WHO) criteria for SM. Advanced SM includes: ASM, SM-AHN, wherein the AHN does not require immediate alternative therapy, such as acute myeloid leukemia [AHNs that are eligible include: low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment for SM only, myeloproliferative neoplasms (MPNs), MDS/MPN, and HES/CEL] and MCL
    3. Malignant glioma patients with genomic alterations of PDGFRA and/or KIT.
    4. Other solid tumor patients that have alterations in genes encoding kinases that are targets of DCC-2618. This includes KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2.
  2. Patients with known CNS metastases may participate provided that:

    1. they are stable (ie, without evidence of progression by magnetic resonance imaging [MRI]) for at least 4 weeks prior to the first dose study drug (patients with active disease may be eligible following discussion between the Investigator and the Sponsor),
    2. all neurologic symptoms have been stable for 2 weeks prior to the first dose of study drug,
    3. patients do not require use of enzyme-inducing antiepileptic drugs.
    4. patients that require steroids must be on a stable dose for 2 weeks prior to the first dose of study drug
  3. Patients with solid tumors (with the exception of glial tumors and tumors that are anatomically inaccessible) must have an archival tumor biopsy sample as long as no anticancer therapy was administered since the sample was collected; otherwise, a current biopsy is required.
  4. Male or female patients ≥18 years of age.
  5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.
  6. Female patients of childbearing potential must have a negative serum beta‑human chorionic gonadotropin (β-hCG) pregnancy test within 28 days prior to the start of study drug.
  7. Patients of child-bearing age must agree to use a double contraception method
  8. The patient, or legally authorized representative, is capable of understanding and complying with the protocol and has signed the informed consent document. Signed informed consent form must be obtained before any study‑specific procedures are performed.
  9. Patients with solid tumors must have at least 1 measurable lesion according to RECIST Version 1.1

    • A non-brain lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion before study enrollment.

  10. Adequate organ function and bone marrow function as indicated by the following central laboratory assessments performed within 14 days prior to the first dose of study drug.

Exclusion Criteria

Patients meeting any of the following criteria will be excluded from the study:

  1. GIST patients with wild type or unknown KIT and PDGFRA status
  2. Patients with SM or other hematologic malignancies will be excluded if the following apply:

    1. SM patients with wild type KIT mutational status.
    2. SM patients with neutropenia accompanied by fever or infection, or thrombocytopenia associated with clinically significant bleeding.

      • Patients with an infection that is well controlled with antibiotics are eligible if there is an immediate need for treatment

    3. SM-AHN patients diagnosed with:

    i. SM with MDS (SM-MDS) who require treatment for MDS. ii. Patients requiring immediate treatment for AHN including, but not limited to, SM-AML.

    d) Patients with leukemias, with the exception of MCL and CEL, that have progressed after imatinib.

    e) Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a known target of DCC-2618.

  3. Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to the administration of study drug, with the exception of hydroxyurea that is allowed to control white blood cell count. For prior therapies with a half-life longer than 3 days, the interval must be at least 28 days prior to the first administration of study drug.
  4. Unresolved toxicity NCI CTCAE Version 4.03 (ie, >Grade 1 or baseline) from previous anticancer therapy, excluding alopecia.
  5. New York Heart Association class III and 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.
  6. Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before start of study drug.
  7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) within the 3 months before start of study drug. Patients with venous thrombotic events ≥3 months before start of study drug on stable anticoagulation therapy are eligible.
  8. Baseline prolongation of the rate-corrected QT interval based on repeated demonstration of QTcF >450 ms in males or >470 ms in females or history of long QT interval corrected (QTc) syndrome.
  9. LVEF <50% or below the lower limit of normal (whichever is higher).
  10. Major surgery within 4 weeks of the first dose of study drug; following major surgeries >4 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, or active hepatitis C infection
  14. If female, the patient is pregnant or lactating.
  15. Known allergy or hypersensitivity to any component of the investigational drug product.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02571036

Contacts
Contact: Jama Pitman jpitman@deciphera.com

Locations
United States, Arizona
Honor Health Recruiting
Scottsdale, Arizona, United States
United States, California
UCLA Not yet recruiting
Los Angeles, California, United States
Stanford Not yet recruiting
Palo Alto, California, United States
UCSF Not yet recruiting
San Francisco, California, United States
United States, Florida
University of Miami Recruiting
Miami, Florida, United States
United States, Massachusetts
Dana Farber Recruiting
Boston, Massachusetts, United States
United States, New York
MKKCC Not yet recruiting
New York, New York, United States
United States, Oregon
OHSU Recruiting
Portland, Oregon, United States
United States, Pennsylvania
Fox Chase Cancer Center Not yet recruiting
Philadelphia, Pennsylvania, United States
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States
United States, Utah
Huntsman Cancer Institute Not yet recruiting
Salt Lake City, Utah, United States
Canada
Princess Margaret Recruiting
Toronto, Canada
Sponsors and Collaborators
Deciphera Pharmaceuticals LLC
Investigators
Study Director: Deciphera Pharmaceuticals, LLC Deciphera Pharmaceuticals LLC
  More Information

Responsible Party: Deciphera Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT02571036     History of Changes
Other Study ID Numbers: DCC-2618-01-001
Study First Received: October 5, 2015
Last Updated: August 4, 2017

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Deciphera Pharmaceuticals LLC:
Gastrointestinal stromal tumors (GIST)
systemic mastocytosis (SM)
PDGFR-alpha
KIT
mast cell leukemia (MCL)
mast cell disease (MCD)
DCC-2618
melanoma
aggressive systemic mastocytosis (ASM)

Additional relevant MeSH terms:
Aggression
Gastrointestinal Stromal Tumors
Mastocytosis
Mastocytosis, Systemic
Behavioral Symptoms
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Skin Diseases

ClinicalTrials.gov processed this record on August 18, 2017