A Multicenter Phase 1, Open-Label Study of DCC-2618 to Assess Safety, Tolerability, Efficacy, and Pharmacokinetics in Patients with Advanced Malignancies
- Conditions
- Advanced Canceradvanced malignancies100243241001799010027655
- Registration Number
- NL-OMON55457
- Lead Sponsor
- Deciphera Pharmaceuticals, LLC
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
Inclusion Criteria
Patients must meet the following criteria to be eligible to enroll in the study:
1. Patients must have histologically confirmed solid tumors or hematologic
malignancies. Eligible patients include the following:
a. GIST patients must have a KIT or PDGFRA mutation and must have progressed on
or had an intolerability to at least 1 line of systemic anticancer therapy:
i. Patients with a pre-existing resistance mutation to an approved line of
therapy are eligible. For example, imatinib resistant mutations including KIT
Exon 17 and PDGFRA D842V.
b. Systemic mastocytosis (SM) patients must have a confirmed diagnosis
(confirmed by a central independent pathologist) of advanced SM according to
2016 World Health Organization (WHO) criteria for SM (15) 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) as outlined in Table 3 of the 2013 International Working Group
Myeloproliferative Neoplasms Research and Treatment (IWG MRT) & European
Competence Network on Mastocytosis (ECNM) consensus response criteria (Appendix
10.5); please see below for MCL exception.
Advanced SM includes:
i. Aggressive SM (ASM),
ii. 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, 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 PDGFR (eg, HES or CEL) must
have a diagnosis confirmed by a central independent pathologist and 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.
i. Patients must not require use of enzyme-inducing antiepileptic drugs
ii. Patients that require steroids must be on a stable dose for 2 weeks prior
to the first dose of study drug.
d. 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. Patients must have received approved treatments known to provide
clinical benefit prior to study entry.
e. Melanoma patients with mutations and/or amplification potentially conferring
sensitivity to DCC-2618 including KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2
(KDR).
i. Patients must have a h
Exclusion Criteria
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:
a) 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
b) SM-AHN patients diagnosed with:
i. SM with MDS (SM-MDS) who require treatment.
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. This includes, but is
not limited to, fusions/mutations of fibroblast growth factor receptor 1
(FGFR1), Janus kinase 2 (JAK2), and Abelson murine leukemia viral oncogene
(ABL).
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. 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.
5. New York Heart Association class III or 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 syndrome.
9. LVEF <50% or below the institute 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 vir
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Escalation Phase:<br /><br>The primary objectives are to:<br /><br>• Determine the safety and tolerability of oral DCC-2618<br /><br>• Determine a maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)<br /><br>of oral DCC-2618<br /><br><br /><br>Expansion Phase:<br /><br>The primary objectives are to:<br /><br>• Further evaluate the safety and tolerability of oral DCC-2618<br /><br>• Determine the antitumor activity of DCC-2618 in all diseases under study</p><br>
- Secondary Outcome Measures
Name Time Method <p>Escalation Phase:<br /><br>The secondary objectives are to:<br /><br>• Determine the pharmacokinetic (PK) profile of oral DCC-2618<br /><br>• Document preliminary evidence of DCC-2618 antitumor activity<br /><br><br /><br><br /><br>Expansion Phase:<br /><br>The secondary objectives are to:<br /><br>• Determine the PK, including population PK, profile of oral DCC-2618<br /><br>• Evaluate the safety and tolerability of the RP2D of oral DCC-2618 in a cohort<br /><br>of patients with moderate to severe renal impairment<br /><br>• Determine allele fraction of KIT and PDGFRA mutations in plasma cfDNA and<br /><br>compare it with mutation allele fraction in GIST tumor tissue and their<br /><br>association with prior treatment and study drug response</p><br>