Phase I Study to Assess the Safety, Tolerability, and Pharmacokinetics of Orally Administered CUDC-101 in Cancer Patients

February 8, 2018 updated by: Curis, Inc.

A Phase I Open Label, Multicenter, Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Orally Administered CUDC-101 in Subjects With Advanced and Refractory Solid Tumors

The main purpose of this study is to determine the safety and tolerability of orally administered CUDC-101 in cancer patients, and to determine a dose for further testing. This study will also determine how well CUDC-101 is absorbed into the blood after being given orally, assess CUDC-101 blood levels and what happens to the study drug in the body, and study how the body reacts to the study drug and what effects it has on tumors. CUDC-101 has been administered to cancer patients as an intravenous (IV) infusion in other research studies, but has not been studied when given orally.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • Texas
      • San Antonio, Texas, United States, 78229
        • Southern Texas Accelerated Research Therapeutics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Subjects with a histopathologically confirmed diagnosis of advanced solid tumor.
  2. Subjects must have no further standard of care options.
  3. Measurable or non-measurable disease
  4. Age ≥ 18 years
  5. ECOG performance status ≤ 2
  6. Life expectancy ≥ 3 months
  7. Women of child bearing potential must have a negative serum pregnancy test.
  8. Absolute neutrophil count ≥ 1,500/µL; platelets ≥ 100,000/µL; creatinine ≤ 1.5x upper limit of normal (ULN); total bilirubin ≤ 1.5x ULN; AST/ALT ≤ 2.5x ULN. For subjects with documented liver metastases, the AST/ALT may be ≤ 5x ULN
  9. Serum magnesium and potassium within normal limits (may be supplemented to achieve normal values).
  10. Subjects with brain metastases are eligible if controlled on a stable dose of ≤ 10mg prednisone/day or its equivalent dose of steroids.
  11. Men and women of child bearing potential must agree to use adequate birth control throughout their participation in the study and for 60 days following the last study treatment.
  12. Able to provide written informed consent and to follow protocol requirements.

Exclusion Criteria:

  1. Systemic anticancer therapy within 28 days prior to study treatment. Subjects with prostate cancer on LHRH hormonal therapy may be enrolled and continue on this therapy.
  2. Use of any investigational agent(s) within 21 days prior to study treatment.
  3. Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
  4. Subjects receiving moderate or strong CYP3A4 or CYP2D6 inhibitors within 7 days prior to study treatment (See Appendix C for examples).
  5. Serious infection requiring systemic antibiotic therapy within 14 days prior to study treatment.
  6. Known gastrointestinal condition that would interfere with swallowing or the oral absorption or tolerance of CUDC-101.
  7. Ongoing diarrhea of any grade (per NCI CTCAE v4.03).
  8. Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis.
  9. Unstable or clinically significant concurrent medical condition that would, in the opinion of the Investigator, jeopardize the safety of a subject and/or their compliance with the protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: CUDC-101
200-500 mg CUDC-101, orally administered, twice daily, in continuous 21 day cycles until disease progression or other discontinuation criteria are met.
Drug: CUDC-101
200-500 mg CUDC-101, orally administered, twice daily, in continuous 21 day cycles until disease progression or other discontinuation criteria are met.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose of oral CUDC-101 in subjects with advanced and refractory solid tumors
Time Frame: 21 days (1 cycle of study treatment)
The highest dose level studied at which fewer than 2 out of 6 subjects (< 33%) experience a dose limiting toxicity (DLT).
21 days (1 cycle of study treatment)
Assess the bioavailability (BA) of orally administered CUDC-101
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose on the first and second day of study drug dosing.
Comparison of area under the plasma concentration time curve (AUC) following intravenous and oral administrations.
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose on the first and second day of study drug dosing.
Assess the pharmacokinetics (PK) of orally administered CUDC-101
Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose on the ninth day of study drug dosing
Pharmacokinetic parameters will include AUC, maximum plasma concentration (Cmax),half-life (T1/2), clearance (Cl) and volume of distribution (Vd).
Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose on the ninth day of study drug dosing

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Assess the safety and tolerability of continuous orally administered CUDC-101
Time Frame: 18 months
Number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE, v4.0).
18 months
Evaluate biomarkers of CUDC-101 activity
Time Frame: Day 1 and Day 7 of Cycle 1 dosing.
Pre- and post-dose changes in acetylated histone H3 protein levels in peripheral blood mononuclear cells (PBMCs), as well as skin and tumor biopsy samples (where available).
Day 1 and Day 7 of Cycle 1 dosing.
Assess preliminary anti-cancer activity
Time Frame: 18 months
Occurrences of complete response, partial response, stable disease and progressive disease as determined by the Response Evaluation Criteria In Solid Tumors (RECIST v1.1).
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Curis, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2012

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2012

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 25, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 4, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 8, 2012

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 12, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 8, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CUDC-101-105

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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