AzTrials
AzTrials

Gastrointestinal Stromal TumorsPhase 1NCT02571036

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

A Phase 1 study testing DCC-2618 in people with Gastrointestinal Stromal Tumors and Advanced Systemic Mastocytosis, run by Deciphera Pharmaceuticals, LLC at 26 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DCC-2618
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
282 participants
Where
26 sitesin 6 countries
Study dates
Nov 2015to 29 Apr 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must meet the following criteria to be eligible to enroll in the study:
  • Male or female patients ≥18 years of age.
  • Patients must have histologically confirmed solid tumors or hematologic malignancies. Eligible patients include the following:
  • 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.
  • 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. Patients with imatinib-sensitive KIT mutations must have progressed on or were intolerant to a tyrosine kinase inhibitor. 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; please see below for MCL exception.
  • Advanced SM includes:
Show all 21Show fewer
  • Aggressive SM (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, unclassifiable MDS, and HES/CEL.
  • MCL
  • Patients with histopathologically-confirmed MCL without a C-finding are eligible.
  • Symptomatic SSM
  • By definition, SSM patients must have at least 2 B-findings, and clinically significant symptom burden (eg, flushing, diarrhea, etc.) despite maximal treatment with approved agents to treat mediator symptoms, such as antihistamines and cromolyn sodium.
  • 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.
  • 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.
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.
  • Adequate organ function and bone marrow function.

Who cannot join

  • Patients meeting any of the following criteria will be excluded from the study:
  • GIST patients with wild type or unknown KIT or PDGFRA status.
  • Patients with SM or other hematologic malignancies will be excluded if the following apply:
  • 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.
  • SM-AHN patients diagnosed with:
Show all 21Show fewer
  • SM with MDS who require treatment for MDS. ii. Patients requiring immediate treatment for AHN.
  • Patients with leukemias, with the exception of MCL and CEL, that have progressed after imatinib.
  • Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a known target of DCC-2618.
  • Prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of DCC-2618. Patients receiving adjuvant cancer treatment are not eligible if those medications are potentially active against GIST or excluded per protocol.
  • 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.
  • Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before start of study drug.
  • 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.
  • 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.
  • Left ventricular ejection fraction (LVEF) <50% or below the lower limit of normal (whichever is higher).
  • 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.
  • Any other clinically significant comorbidities.
  • Illnesses that could affect oral absorption.
  • 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.
  • If female, the patient is pregnant or lactating.
  • 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.

Trial locations and contacts

26 sites in 6 countries.

26 sites in 6 countries

United States16 sites

  • Dana Farber Cancer Institute (GIST, mastocytosis, glial malignancies, other solid tumors)

    Boston, Massachusetts, 02215

  • MD Anderson Cancer Center (GIST, mastocytosis, glial malignancies, other solid tumors)

    Houston, Texas, 77030

  • Mayo Clinic (GIST, mastocytosis, glial malignancies, other solid tumors)

    Jacksonville, Florida, 32224

  • UCLA Hematology Center (mastocytosis)

    Los Angeles, California, 90024

  • UCLA (glial malignancies only)

    Los Angeles, California, 90095

  • University of Miami (GIST, mastocytosis, glial malignancies, other solid tumors)

    Miami, Florida, 33136

  • Colombia University Medical Center (mastocytosis)

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center (GIST, mastocytosis, glial malignancies, other solid tumors)

    New York, New York, 10065

  • Stanford University Comprehensive Cancer Center (GIST)

    Palo Alto, California, 94304

  • Stanford University Hematology Clinic (mastocytosis)

    Palo Alto, California, 94305

  • Fox Chase Cancer Center (GIST only)

    Philadelphia, Pennsylvania, 19111

  • OHSU (GIST & mastocytosis only)

    Portland, Oregon, 97239

  • Virginia Commonwealth University School of Medicine (mastocytosis)

    Richmond, Virginia, 23219

  • Huntsman Cancer Institute (GIST, mastocytosis, glial malignancies, other solid tumors)

    Salt Lake City, Utah, 84103

  • UCSF (glial malignancies only)

    San Francisco, California, 94143

  • Honor Health (GIST, mastocytosis, other solid tumors)

    Scottsdale, Arizona, 85258

Other trials in United States

Germany5 sites

  • Uniklinik RWTH Aachen (mastocytosis, GIST, and other solid tumors)

    Aachen, 52074

  • HELIOS Klinikum Berlin-Buch (GIST, and other solid tumors)

    Berlin, 13125

  • Essen University Hospital (mastocytosis, GIST, and other solid tumors)

    Essen, 45147

  • Freiburg University Hospital (mastocytosis, and other solid tumors)

    Freiburg im Breisgau, 79106

  • University Medical Centre Mannheim (mastocytosis)

    Mannheim, 68167

Other trials in Germany

United Kingdom2 sites

  • Guy's Hospital (mastocytosis only)

    London, SE1 9RT

  • Royal Marsden Hospital (GIST, glial malignancies, other solid tumors)

    London, SW3 6JJ

Other trials in United Kingdom

Canada1 site

  • Princess Margaret Cancer Centre (GIST, other solid tumors)

    Toronto, M5G IX5

Other trials in Canada

Italy1 site

  • University Hospital of Verona (mastocytosis)

    Verona, 37134

Other trials in Italy

Netherlands1 site

  • Leiden University Medical Center (GIST and other solid tumors)

    Leiden, 2333

Other trials in Netherlands

About this study

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

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. All active patients (from both dose-escalation and expansion phases) will then transition into an extension phase.

Being tested
DCC-2618
Keywords
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, malignant gliomas
Medical subject headings
Gastrointestinal Stromal Tumors, Mastocytosis, Systemic, Leukemia, Mast-Cell, Mast Cell Activation Disorders, Melanoma, Sarcoma, Neoplasms, Germ Cell and Embryonal, Penile Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DCC-2618Drug

    Also called ripretinib

    50 mg formulated tablets

  • DCC-2618Drug

    Also called ripretinib

    10 mg and 50 mg formulated tablets

Study groups in NCT02571036
Study groupRoleWhat they receive
EscalationExperimentalEscalation 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]
Receives: Drug: DCC-2618
Expansion Cohort 1Experimental150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received 3 prior therapies. [Closed for Enrollment]
Receives: Drug: DCC-2618
Expansion Cohort 2Experimental150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received 4 prior therapies. [Closed for Enrollment]
Receives: Drug: DCC-2618
Expansion Cohort 3Experimental150 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]
Receives: Drug: DCC-2618
Expansion Cohort 4Experimental150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with systemic mastocytosis and other hematologic malignancies.[Closed for Enrollment]
Receives: Drug: DCC-2618
Expansion Cohort 5Experimental150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with malignant gliomas.[Closed for Enrollment]
Receives: Drug: DCC-2618
Expansion Cohort 6Experimental150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with other solid tumors. [Closed for Enrollment]
Receives: Drug: DCC-2618
Expansion Cohort 7Experimental150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with melanomas. [Closed for Enrollment]
Receives: Drug: DCC-2618
Expansion Cohort 8Experimental150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with soft tissue sarcomas.[Closed for Enrollment]
Receives: Drug: DCC-2618
Expansion Cohort 9Experimental150 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). [Closed for Enrollment]
Receives: Drug: DCC-2618
Expansion Cohort 10Experimental150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST and other solid tumors with renal impairment. [Closed for Enrollment]
Receives: Drug: DCC-2618
Extension CohortExperimental150 mg DCC-2618 given once daily in repeated 28-day cycles for active patients from the Escalation and Extension Phases.
Receives: Drug: DCC-2618

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety/tolerability of oral DCC-2618: incidence of adverse events

    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.

    Measured: Approximately 24 months

  2. Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose

    Measured: 18 months

  3. Expansion Phase: Assess Antitumor Activity of DCC-2618 in all diseases

    Objective response rate (ORR); Disease control rate (DCR)

    Measured: Approximately 24 months

Secondary outcomes (2)

  1. Determine the PK profile of oral DCC-2618

    Measured: Predose and up to 24 hours postdose (Cycle = 28 Days)

  2. Escalation Phase: Assess Antitumor Activity of DCC-2618 in patients with advanced malignancies

    Objective response rate (ORR); Disease control rate (DCR)

    Measured: Approximately 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2015 (estimated)
  2. Study startNov 2015
  3. Primary completion29 Apr 2022
  4. Study completion29 Apr 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
282 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02571036
Sponsor's protocol ID
DCC-2618-01-001
Status last verified
Dec 2023
First submitted
5 Oct 2015
Last updated
13 Dec 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes

Publications

  • Janku F, Abdul Razak AR, Chi P, Heinrich MC, von Mehren M, Jones RL, Ganjoo K, Trent J, Gelderblom H, Somaiah N, Hu S, Rosen O, Su Y, Ruiz-Soto R, Gordon M, George S. Switch Control Inhibition of KIT and PDGFRA in Patients With Advanced Gastrointestinal Stromal Tumor: A Phase I Study of Ripretinib. J Clin Oncol. 2020 Oct 1;38(28):3294-3303. doi: 10.1200/JCO.20.00522. Epub 2020 Aug 17.

    PubMed 32804590

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DCC-2618 in people with Gastrointestinal Stromal Tumors and Advanced Systemic Mastocytosis, run by Deciphera Pharmaceuticals, LLC at 26 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, Germany, United Kingdom, Canada, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety/tolerability of oral DCC-2618: incidence of adverse events (time frame: Approximately 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02571036, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in