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Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor (CDAi) With Oral Decitabine in Subjects With Solid Tumors

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ClinicalTrials.gov Identifier: NCT03875287
Recruitment Status : Recruiting
First Posted : March 14, 2019
Last Update Posted : June 13, 2019
Sponsor:
Collaborator:
Astex Pharmaceuticals
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
This is a phase 1 study of the combination of cedazuridine with decitabine in patients with solid tumors. At least 6 patients will be enrolled per treatment level to assess optimal hypomethylation and toxicity (up to 30 patients total).

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: Decitabine Drug: Cedazuridine Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase I Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor (CDAi) With Oral Decitabine in Subjects With Solid Tumors
Actual Study Start Date : April 17, 2019
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Decitabine

Arm Intervention/treatment
Experimental: Decitabine and Cedazuridine
Treatment will be administered on an outpatient basis. Cycle length is 28 days. The dose of cedazuridine is fixed at 100mg and the dose and duration of decitabine will vary depending on when a patient enters the study.
Drug: Decitabine

DOSING REGIMEN(S):

Level -1 5mg daily days 1-10

Level 1 5mg daily days 1-14

Level 2 10mg daily days 1-14

Level 3 15mg daily days 1-14

Other Name: Dacogen

Drug: Cedazuridine

DOSING REGIMEN(S):

Level -1 100mg daily days 1-10

Level 1 100mg daily days 1-14

Level 2 100mg daily days 1-14

Level 3 100mg daily days 1-14





Primary Outcome Measures :
  1. Safety and tolerability of combination cedazuridine with decitabine as assessed by number of participants who experience adverse events [ Time Frame: up to 2 years ]
    Number of participants who have experienced grade 3 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)

  2. Maximum Tolerated Dose (MTD) as determined by number of participants with of dose limiting toxicities (DLT) [ Time Frame: up to 2 years ]
    Maximum tolerated dose will be determined by the maximum dose at which the least number of participants experience dose-limiting toxicity. The dose limiting toxicity is defined using the Common Terminology Criteria for Adverse Events (CTCAE).


Secondary Outcome Measures :
  1. Pharmacokinetics of ASTX727 in solid tumor patients as measured by total exposure [ Time Frame: Day 2 ]
    Total exposure will be calculated as area under the plasma concentration-time curve (AUC) by using non-compartmental methods (Winonlin, version 5.3 or newer) and/or compartmental modeling (Adapt II, release 4.0)

  2. Pharmacokinetics of ASTX727 in solid tumor patients as measured by maximum concentration (Cmax) [ Time Frame: Day 2 ]
    Cmax (mmol/L) is defined as the maximum concentration of ASTX727 in blood.

  3. Pharmacokinetics of ASTX727 in solid tumor patients as measured by time to maximum concentration (Tmax) [ Time Frame: Day 2 ]
    Tmax (minutes) is defined as the time to reach maximum concentration of ASTX727 in blood.

  4. Objective response rate (ORR) in solid tumor patients who are treated with ASTX727 [ Time Frame: up to 2 years ]
    Proportion of participants who had measurable disease at baseline and have been re-evaluated after at least 1 cycle of therapy with observed reduction in tumor burden as defined by RECIST 1.1: Complete response (CR)= disappearance of all target lesions, Partial response (PR)= at least 30% decrease in sum of diameters of target lesions



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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have advanced, unresectable, and/or metastatic solid tumor malignancy that is histologically or cytologically confirmed.
  • Patients must have received at least 2 lines of therapy in the advanced/metastatic setting (if 2 lines exist) and have no other possible therapies or refuse therapies that have shown clinical benefit for their condition.
  • ECOG performance status <1
  • Ability to understand and the willingness to sign a written informed consent document.
  • Patients must have measurable disease
  • Ability to swallow oral medications

Exclusion Criteria:

  • Participants who have had chemotherapy or radiotherapy within 3 weeks
  • Participants may not be receiving any other investigational agents.
  • Active hepatitis B or hepatitis C infection.
  • Active or untreated gastric or duodenal ulcer
  • Symptomatic bowel obstruction within 3 months prior to screening visit.
  • Symptomatic ascites in the last 4 weeks

Other protocol defined inclusion/exclusion criteria may apply.


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): NCT03875287


Contacts
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Contact: Angela Scardina, RN 443-287-6456 phase1trials@jhmi.edu

Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Astex Pharmaceuticals
Investigators
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Principal Investigator: Nilofer Azad, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03875287     History of Changes
Other Study ID Numbers: J18115
IRB00182038 ( Other Identifier: JHM IRB )
ASTX727 ( Other Identifier: Astex Pharmaceuticals )
First Posted: March 14, 2019    Key Record Dates
Last Update Posted: June 13, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors