LymphomaPhase 1NCT01908413
Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-427 When Given to Patients With Advanced and Refractory Solid Tumors or Lymphoma
A Phase 1 study testing CUDC-427 in people with Lymphoma, run by Curis, Inc. at 2 sites in United States.
Trial summary
This is a phase I, open-label, dose-escalation study of CUDC-427 in patients with advanced or refractory solid tumors or lymphoma. CUDC-427 is a drug that is designed to antagonize proteins that prevent or interfere with cell death. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- CUDC-427
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2013to Nov 2015
- 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
- Subjects of ≥ 18 years of age.
- Histologically or cytologically confirmed diagnosis of advanced solid tumor or lymphoma that has progressed following standard therapy or for which there is no standard or curative therapy.
- Measurable or non-measureable disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Recovery to Grade 1 or baseline of any toxicity due to prior systemic treatments (excluding alopecia).
- Absolute neutrophil count 1,500/L; platelets 100,000/L; creatinine 1.5x upper limit of normal (ULN); total bilirubin 1.5x ULN; aspartate aminotransferase/ alanine aminotransferase (AST/ALT) 2.5x ULN; Tbili </= ULN. For subjects with documented liver metastases, the AST/ALT may be 5x ULN.
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- Life expectancy of at least 3 months.
- Subjects with adequately treated, stable brain metastases are eligible if symptomatically controlled on a stable dose of ≤ 10mg prednisone/day or its equivalent dose of steroids.
- Women of child bearing potential must have a negative serum or urine pregnancy test.
- Men and women of child bearing potential must agree to use adequate birth control from the time of screening through 30 days after the last dose of study drug.
- Able to provide written informed consent and to follow protocol requirements.
Who cannot join
- Systemic anticancer therapy within 3 weeks of study entry, except for nitrosoureas or mitomycin C (6 weeks). Subjects with prostate cancer receiving luteinizing hormone-releasing hormone (LHRH) hormonal therapy may be enrolled and continue on this therapy.
- Other investigational agents within 21 days prior to the first dose of study drug.
- Prior treatment with an antagonist of inhibitors of apoptosis proteins.
- History of chronic liver disease, hepatic cirrhosis, current cholestatic disease, active hepatic infection, non-alcoholic steatohepatitis (NASH), current alcohol or substance abuse (liver metastases due to disease under study are permitted).
- Pregnant or lactating/breast-feeding women.
- Ongoing treatment with chronic immunosuppressants.
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- Known gastrointestinal condition that would interfere with swallowing or the oral absorption or tolerance of CUDC-427.
- Ongoing diarrhea defined as more than 1 watery stool/day.
- Infection requiring intravenous antibiotic therapy within 14 days prior to the first dose of study drug.
- Clinically significant cardiac history, such as:
- 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.
- Previous history of QTc prolongation as a result of other medication that required discontinuation of that medication.
- Congenital long QT syndrome or first degree relative with unexplained sudden death under 40 years of age.
- QTc with Fridericia's (QTcF) correction that is unmeasurable or ≥ 480 msec on screening ECG. If a subject has a QTcF ≥ 480 sec on the screening ECG, the ECG may be repeated twice (at least 24 hour apart) and the mean QTcF from the three screening ECGs must be < 480 msec in order for the subject to be eligible for the study.
- Ejection fraction (EF) by ECHO < 55% (abnormal values may be repeated x2 and the mean of the 3 tests used for determination)
- Use of any concomitant medication (within 7 days of starting treatment) that may cause QTc prolongation, inducing Torsades de Pointes
- 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.
- Known human immunodeficiency virus (HIV) positive.
- Prior malignancy within 2 years except non-melanoma skin cancer and other in situ carcinomas that have been surgically treated with curative intent.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Southern Texas Accelerated Research Therapeutics
San Antonio, Texas, 78229
About this study
Official title: A Phase I Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral CUDC-427, an Antagonist of Inhibitors of Apoptosis (IAP) Proteins, When Administered in Subjects With Advanced and Refractory Solid Tumors or Lymphoma
This is a phase I, open-label, dose-escalation study of CUDC-427 in patients with advanced or refractory solid tumors or lymphoma. CUDC-427 is a drug that is designed to antagonize proteins that prevent or interfere with cell death. The study is designed to assess the safety, including the maximum tolerated dose, the pharmacokinetics, and the anti-cancer activity of CUDC-427.
Read the detailed description
This is a Phase I, open-label, multicenter, dose-escalation study to evaluate the safety and tolerability of CUDC-427 as a single agent administered orally, in subjects with advanced and refractory solid tumors or lymphoma.
Sequential dose escalation cohorts of oral CUDC-427 are planned. Subject enrollment and dose escalation will proceed according to a standard 3+3 design. In the absence of intolerable toxicity, each subject will receive a minimum of 1 cycle (21 days) of study treatment, and may continue to receive additional cycles until disease progression has been documented or other treatment discontinuation criteria have been met.
No intrasubject dose escalation will be allowed. During the dose escalation phase, up to 3 additional subjects may be enrolled at previously cleared dose levels to better define the safety, tolerability and activity of the study treatment. Similarly, an MTD expansion cohort of up to 12 evaluable subjects may also be enrolled.
Safety and tolerability will be assessed by the incidence and severity of adverse events as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE v4.03). A Safety Review Committee comprised of the Medical Monitor, Principal Investigators, and Sponsor representatives, will be convened to review safety information and to decide upon dose escalation and further subject enrollment.
The antitumor activity of study treatment will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), or the Revised Response Criteria for Malignant Lymphoma as appropriate for each subject's tumor type.
Exploratory biological markers of CUDC-427 activity will be assessed in tumor samples (where available), peripheral blood mononuclear cells (PBMC) and plasma.
- Conditions
- Lymphoma
- Being tested
- CUDC-427
- Keywords
- Advanced Solid Tumors, Lymphoma, Open-Label, Dose-Escalation, IAP
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CUDC-427Drug
CUDC-427 as an oral formulation administered daily on a 14 days on/7 days off schedule
| Study group | Role | What they receive |
|---|---|---|
| CUDC-427 | Experimental | Not described Receives: Drug: CUDC-427 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose (MTD) and recommended Phase 2 (monotherapy) dose of oral CUDC-427 administered on a 14 days on/7 days off dosing schedule in subjects with advanced and refractory solid tumors or lymphoma
Measured: 21 days (1 cycle of study treatment)
Secondary outcomes (4)
To assess safety and tolerability
Number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE, v4.0).
Measured: 21 days
To assess pharmacokinetics (PK)
PK parameters to be determined will include apparent oral clearance (Cl/F), apparent volume of distribution (Vd/F), maximum concentration (Cmax), time of maximum concentration (Tmax), half-life (t1/2), area under the curve (AUC), and other relevant parameters.
Measured: The first day of study drug dosing through the sixteenth day of study drug dosing
To evaluate exploratory biological markers of CUDC-427 activity
Exploratory biomarkers that may predict or correlate with CUDC-427 biological activity will be assessed in tumor samples, PBMCs and plasma, such as gene signature profile, cellular inhibitor of apoptosis (cIAP) levels, Ki-67 activity, caspase activity, cytokine levels, and other downstream events of IAP inhibition.
Measured: The first day of study drug dosing through the fifteenth day of study drug dosing
To assess preliminary anti-cancer activity
The Investigator will evaluate each subject for response to therapy according to standard response criteria for each individual subject's tumor type (e.g., Revised Response Criteria for Malignant Lymphoma and RECIST v1.1 for Solid Tumors).
Measured: 3-12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionMar 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Curis, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01908413
- Sponsor's protocol ID
- CUDC-427-101
- Status last verified
- Nov 2016
- First submitted
- 23 Jul 2013
- Last updated
- 1 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral CUDC-427, an Antagonist of Inhibitors of Apoptosis (IAP) Proteins, When Administered in Subjects With Advanced and Refractory Solid Tumors or Lymphoma
- ClinicalTrials.gov ID
- NCT01908413
- Acronym / sponsor ID
- CUDC-427-101
- Conditions
- Lymphoma
- Keywords
- Advanced Solid Tumors, Lymphoma, Open-Label, Dose-Escalation, IAP
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Curis, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 25 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I, open-label, dose-escalation study of CUDC-427 in patients with advanced or refractory solid tumors or lymphoma. CUDC-427 is a drug that is designed to antagonize proteins that prevent or interfere with cell death. The study is designed to assess the safety, including the maximum tolerated dose, the pharmacokinetics, and the anti-cancer activity of CUDC-427.
Detailed description
This is a Phase I, open-label, multicenter, dose-escalation study to evaluate the safety and tolerability of CUDC-427 as a single agent administered orally, in subjects with advanced and refractory solid tumors or lymphoma.
Sequential dose escalation cohorts of oral CUDC-427 are planned. Subject enrollment and dose escalation will proceed according to a standard 3+3 design. In the absence of intolerable toxicity, each subject will receive a minimum of 1 cycle (21 days) of study treatment, and may continue to receive additional cycles until disease progression has been documented or other treatment discontinuation criteria have been met.
No intrasubject dose escalation will be allowed. During the dose escalation phase, up to 3 additional subjects may be enrolled at previously cleared dose levels to better define the safety, tolerability and activity of the study treatment. Similarly, an MTD expansion cohort of up to 12 evaluable subjects may also be enrolled.
Safety and tolerability will be assessed by the incidence and severity of adverse events as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE v4.03). A Safety Review Committee comprised of the Medical Monitor, Principal Investigators, and Sponsor representatives, will be convened to review safety information and to decide upon dose escalation and further subject enrollment.
The antitumor activity of study treatment will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), or the Revised Response Criteria for Malignant Lymphoma as appropriate for each subject's tumor type.
Exploratory biological markers of CUDC-427 activity will be assessed in tumor samples (where available), peripheral blood mononuclear cells (PBMC) and plasma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CUDC-427 | Experimental | Drug: CUDC-427 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subjects of ≥ 18 years of age.
- Histologically or cytologically confirmed diagnosis of advanced solid tumor or lymphoma that has progressed following standard therapy or for which there is no standard or curative therapy.
- Measurable or non-measureable disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Recovery to Grade 1 or baseline of any toxicity due to prior systemic treatments (excluding alopecia).
Key exclusion criteria (19 listed)
- Systemic anticancer therapy within 3 weeks of study entry, except for nitrosoureas or mitomycin C (6 weeks). Subjects with prostate cancer receiving luteinizing hormone-releasing hormone (LHRH) hormonal therapy may be enrolled and continue on this therapy.
- Other investigational agents within 21 days prior to the first dose of study drug.
- Prior treatment with an antagonist of inhibitors of apoptosis proteins.
- History of chronic liver disease, hepatic cirrhosis, current cholestatic disease, active hepatic infection, non-alcoholic steatohepatitis (NASH), current alcohol or substance abuse (liver metastases due to disease under study are permitted).
- Pregnant or lactating/breast-feeding women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CUDC-427CUDC-427 as an oral formulation administered daily on a 14 days on/7 days off schedule | Drug | CUDC-427 |
Primary outcome
To determine the maximum tolerated dose (MTD) and recommended Phase 2 (monotherapy) dose of oral CUDC-427 administered on a 14 days on/7 days off dosing schedule in subjects with advanced and refractory solid tumors or lymphoma
Time frame: 21 days (1 cycle of study treatment)
4 secondary outcomes
To assess safety and tolerability
Time frame: 21 days
To assess pharmacokinetics (PK)
Time frame: The first day of study drug dosing through the sixteenth day of study drug dosing
To evaluate exploratory biological markers of CUDC-427 activity
Time frame: The first day of study drug dosing through the fifteenth day of study drug dosing
To assess preliminary anti-cancer activity
Time frame: 3-12 weeks
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CUDC-427 in people with Lymphoma, run by Curis, Inc. at 2 sites in United States.
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 11 inclusion and 19 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: stopped early, as of the sponsor's last update on 1 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 was stopped early. Results are not available in the source record.
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?
To determine the maximum tolerated dose (MTD) and recommended Phase 2 (monotherapy) dose of oral CUDC-427 administered on a 14 days on/7 days off dosing schedule in subjects with advanced and refractory solid tumors or lymphoma (time frame: 21 days (1 cycle of study treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Dec 2016.