A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies
NCT ID: NCT02571036
Last Updated: 2023-12-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
282 participants
INTERVENTIONAL
2015-11-30
2022-04-29
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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. \[Closed for Enrollment\]
DCC-2618
10 mg and 50 mg formulated tablets
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. \[Closed for Enrollment\]
DCC-2618
50 mg formulated tablets
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. \[Closed for Enrollment\]
DCC-2618
50 mg formulated tablets
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. \[Closed for Enrollment\]
DCC-2618
50 mg formulated tablets
Expansion Cohort 4
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with systemic mastocytosis and other hematologic malignancies.\[Closed for Enrollment\]
DCC-2618
50 mg formulated tablets
Expansion Cohort 5
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with malignant gliomas.\[Closed for Enrollment\]
DCC-2618
50 mg formulated tablets
Expansion Cohort 6
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with other solid tumors. \[Closed for Enrollment\]
DCC-2618
50 mg formulated tablets
Expansion Cohort 7
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with melanomas. \[Closed for Enrollment\]
DCC-2618
50 mg formulated tablets
Expansion Cohort 8
150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with soft tissue sarcomas.\[Closed for Enrollment\]
DCC-2618
50 mg formulated tablets
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). \[Closed for Enrollment\]
DCC-2618
50 mg formulated tablets
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. \[Closed for Enrollment\]
DCC-2618
50 mg formulated tablets
Extension Cohort
150 mg DCC-2618 given once daily in repeated 28-day cycles for active patients from the Escalation and Extension Phases.
DCC-2618
50 mg formulated tablets
Interventions
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DCC-2618
50 mg formulated tablets
DCC-2618
10 mg and 50 mg formulated tablets
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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. 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:
i. Aggressive SM (ASM)
ii. 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.
iii. MCL
• Patients with histopathologically-confirmed MCL without a C-finding are eligible.
iv. 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.
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.
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
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 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.
2. SM-AHN patients diagnosed with:
i. SM with MDS who require treatment for MDS. ii. Patients requiring immediate treatment for AHN.
c. Patients with leukemias, with the exception of MCL and CEL, that have progressed after imatinib.
d. Eosinophilic myeloproliferative neoplasm patients: i. Lacking a mutation that is a known target of DCC-2618.
3. 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.
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.
18 Years
ALL
No
Sponsors
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Deciphera Pharmaceuticals, LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Deciphera Pharmaceuticals, LLC
Role: STUDY_DIRECTOR
Deciphera Pharmaceuticals, LLC
Locations
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Honor Health (GIST, mastocytosis, other solid tumors)
Scottsdale, Arizona, United States
UCLA Hematology Center (mastocytosis)
Los Angeles, California, United States
UCLA (glial malignancies only)
Los Angeles, California, United States
Stanford University Comprehensive Cancer Center (GIST)
Palo Alto, California, United States
Stanford University Hematology Clinic (mastocytosis)
Palo Alto, California, United States
UCSF (glial malignancies only)
San Francisco, California, United States
Mayo Clinic (GIST, mastocytosis, glial malignancies, other solid tumors)
Jacksonville, Florida, United States
University of Miami (GIST, mastocytosis, glial malignancies, other solid tumors)
Miami, Florida, United States
Dana Farber Cancer Institute (GIST, mastocytosis, glial malignancies, other solid tumors)
Boston, Massachusetts, United States
Colombia University Medical Center (mastocytosis)
New York, New York, United States
Memorial Sloan Kettering Cancer Center (GIST, mastocytosis, glial malignancies, other solid tumors)
New York, New York, United States
OHSU (GIST & mastocytosis only)
Portland, Oregon, United States
Fox Chase Cancer Center (GIST only)
Philadelphia, Pennsylvania, United States
MD Anderson Cancer Center (GIST, mastocytosis, glial malignancies, other solid tumors)
Houston, Texas, United States
Huntsman Cancer Institute (GIST, mastocytosis, glial malignancies, other solid tumors)
Salt Lake City, Utah, United States
Virginia Commonwealth University School of Medicine (mastocytosis)
Richmond, Virginia, United States
Princess Margaret Cancer Centre (GIST, other solid tumors)
Toronto, , Canada
Uniklinik RWTH Aachen (mastocytosis, GIST, and other solid tumors)
Aachen, , Germany
HELIOS Klinikum Berlin-Buch (GIST, and other solid tumors)
Berlin, , Germany
Essen University Hospital (mastocytosis, GIST, and other solid tumors)
Essen, , Germany
Freiburg University Hospital (mastocytosis, and other solid tumors)
Freiburg im Breisgau, , Germany
University Medical Centre Mannheim (mastocytosis)
Mannheim, , Germany
University Hospital of Verona (mastocytosis)
Verona, , Italy
Leiden University Medical Center (GIST and other solid tumors)
Leiden, , Netherlands
Guy's Hospital (mastocytosis only)
London, , United Kingdom
Royal Marsden Hospital (GIST, glial malignancies, other solid tumors)
London, , United Kingdom
Countries
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References
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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.
Other Identifiers
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DCC-2618-01-001
Identifier Type: -
Identifier Source: org_study_id