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A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT02571036
Recruitment Status : Recruiting
First Posted : October 8, 2015
Last Update Posted : September 17, 2018
Sponsor:
Information provided by (Responsible Party):
Deciphera Pharmaceuticals LLC

Brief 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.

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 320 participants
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
Study Start Date : October 2015
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021


Arm Intervention/treatment
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. [Closed for Enrollment]
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. [Closed for Enrollment]
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. [Closed for Enrollment]
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 therapy and no more than 2 prior therapies. [Closed for Enrollment]
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. [Closed for Enrollment]
Drug: DCC-2618
10 mg and 50 mg formulated tablets

Experimental: Expansion Cohort 7
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with melanomas.
Drug: DCC-2618
10 mg and 50 mg formulated tablets

Experimental: Expansion Cohort 8
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with soft tissue sarcomas.
Drug: DCC-2618
10 mg and 50 mg formulated tablets

Experimental: Expansion Cohort 9
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with germ cell, penile cancer and non-small cell lung carcinoma (NSCLC).
Drug: DCC-2618
10 mg and 50 mg formulated tablets

Experimental: Expansion Cohort 10
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST and other solid tumors with renal impairment.
Drug: DCC-2618
10 mg and 50 mg formulated tablets




Primary Outcome Measures :
  1. Safety/tolerability of oral DCC-2618: incidence of adverse events [ 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.

  2. Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose [ Time Frame: 18 months ]
  3. Expansion Phase: Assess Antitumor Activity of DCC-2618 in all diseases [ Time Frame: Approximately 24 months ]
    Objective response rate (ORR); Disease control rate (DCR)


Secondary Outcome Measures :
  1. Determine the PK profile of oral DCC-2618 [ Time Frame: Predose and up to 24 hours postdose (Cycle = 28 Days) ]
  2. Escalation Phase: Assess Antitumor Activity of DCC-2618 in patients with advanced malignancies [ Time Frame: Approximately 24 months ]
    Objective response rate (ORR); Disease control rate (DCR)



Information from the National Library of Medicine

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

Inclusion Criteria (Escalation and Expansion Phases)

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

  1. Male or female patients ≥18 years of age.
  2. Patients must have histologically confirmed solid tumors or hematologic malignancies. 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 line of systemic anticancer therapy.
    2. SM patients must have a confirmed diagnosis of advanced SM according to 2016 World Health Organization (WHO) criteria for SM and must have documented KIT mutant disease.

    Advanced SM includes: ASM, SM with associated hematologic neoplasm (SM-AHN), wherein the AHN does not require immediate alternative therapy. AHNs that are eligible include: low grade myelodysplastic syndrome (MDS) with a high SM burden who require treatment for SM only, myeloproliferative neoplasms (MPN), MDS/MPN, and HES/CEL, and MCL.

    i. Patients with advanced SM must present with at least 1 eligible C-Finding (organ damage) per 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis consensus response criteria.

    ii. Patients with imatinib-sensitive KIT mutations must have progressed on or were intolerant to a tyrosine kinase inhibitor.

    iii. Patients with histopathologically-confirmed MCL without a C-finding are eligible.

    iv. Patients with symptomatic smoldering systemic mastocytosis (SSM) are eligible.

    v. Patients with hematologic malignancies featuring clonal expansion of eosinophils driven by genomic alterations of KIT or PDGFRA (eg, HES or CEL) are eligible if they have progressed on or are intolerant of imatinib therapy. Patients with de novo imatinib resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are eligible without prior imatinib therapy.

    c. Malignant glioma patients with genomic alterations potentially conferring sensitivity to DCC-2618 including, but not limited to, amplification and/or mutations of PDGFRA and/or KIT.

    d. Other solid tumor patients that have alterations in genes encoding kinases that are targets of DCC-2618. This includes:

    • Melanoma
    • Soft tissue sarcoma patients (including but not limited to: malignant peripheral nerve sheath tumors (MPNST), desmoplastic small round cell tumors (DSRCT), and dermatofibrosarcoma protuberans tumors (DFSP)
    • Other solid tumor patients (non-melanoma, non-STS; specifically germ-cell, penile, and non-small cell lung carcinoma)
    • Renal impairment cohort
  3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.
  4. Adequate organ function and bone marrow function.

Exclusion Criteria (Escalation and Expansion Phases)

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

  1. GIST patients with wild type or unknown KIT or 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 who require treatment for MDS. ii. Patients requiring immediate treatment for AHN.

    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. Has a known additional malignancy that is progressing or required active treatment within 3 years of the first dose of study treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or other in situ cancers.
  4. 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.
  5. Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before start of study drug.
  6. 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.
  7. Baseline prolongation of the rate-corrected QT interval based on repeated demonstration of QT interval corrected by Fridericia's formula (QTcF) >450 ms in males or >470 ms in females or history of long QT interval corrected (QTc) syndrome.
  8. Left ventricular ejection fraction (LVEF) <50% or below the lower limit of normal (whichever is higher).
  9. 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.
  10. Any other clinically significant comorbidities.
  11. Illnesses that could affect oral absorption.
  12. Known human immunodeficiency virus or active hepatitis C infection only if the patient is taking per protocol prohibited medications, active hepatitis B, or active hepatitis C infection.
  13. If female, the patient is pregnant or lactating.
  14. Known allergy or hypersensitivity to any component of the investigational drug product. Patients with history of Stevens-Johnson syndrome on a prior tyrosine kinase inhibitor (TKI) are excluded.

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): NCT02571036


Contacts
Contact: Jama Pitman clinicaltrials@deciphera.com

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Sponsors and Collaborators
Deciphera Pharmaceuticals LLC
Investigators
Study Director: Deciphera Pharmaceuticals, LLC Deciphera Pharmaceuticals LLC

Responsible Party: Deciphera Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT02571036     History of Changes
Other Study ID Numbers: DCC-2618-01-001
First Posted: October 8, 2015    Key Record Dates
Last Update Posted: September 17, 2018
Last Verified: September 2018

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)
soft tissue sarcoma (STS)
germ cell tumors
penile cancer
non-small cell lung carcinoma (NSCLC)
renal impairment

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