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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:

Description

Summary

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.

Official Title

A Multicenter Phase 1, Open-Label Study of DCC-2618 to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced Malignancies

Keywords

Gastrointestinal Stromal Tumors Aggressive Systemic Mastocytosis Advanced Cancers 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)

Eligibility

You can join if…

Open to people ages 18 years and up

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:
  2. 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
  3. 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
  4. Malignant glioma patients with genomic alterations of PDGFRA and/or KIT.
  5. 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.
  6. Patients with known CNS metastases may participate provided that:
  7. 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),
  8. all neurologic symptoms have been stable for 2 weeks prior to the first dose of study drug,
  9. patients do not require use of enzyme-inducing antiepileptic drugs.
  10. patients that require steroids must be on a stable dose for 2 weeks prior to the first dose of study drug
  11. 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.
  12. Male or female patients ≥18 years of age.
  13. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.
  14. 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.
  15. Patients of child-bearing age must agree to use a double contraception method
  16. 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.
  17. 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.

  18. 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.

You CAN'T join if...

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:
  3. SM patients with wild type KIT mutational status.
  4. 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

  5. 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.

  6. 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.
  7. Unresolved toxicity NCI CTCAE Version 4.03 (ie,>Grade 1 or baseline) from previous anticancer therapy, excluding alopecia.
  8. 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.
  9. Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before start of study drug.
  10. 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.
  11. 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.
  12. LVEF <50% or below the lower limit of normal (whichever is higher).
  13. 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.
  14. 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.
  15. Malabsorption syndrome or other illness that could affect oral absorption.
  16. Known human immunodeficiency virus, active hepatitis B, or active hepatitis C infection
  17. If female, the patient is pregnant or lactating.
  18. Known allergy or hypersensitivity to any component of the investigational drug product.

Locations

  • Stanford not yet accepting patients
    Palo Alto, California, United States
  • UCLA not yet accepting patients
    Los Angeles, California, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Deciphera Pharmaceuticals LLC
ID
NCT02571036
Phase
Phase 1
Study Type
Interventional
Last Updated
July 1, 2017
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