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

NCT01908413 | Terminated Phase 1

• 1 other identifier: CUDC-427-101
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief 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. The study is designed to assess the safety, including the maximum tolerated dose, the pharmacokinetics, and the anti-cancer activity of CUDC-427.

Conditions

Lymphoma

Keywords

Advanced Solid Tumors; Lymphoma; Open-Label; Dose-Escalation; IAP

Outcome Measures

Primary Outcomes (1)

• 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

  21 days (1 cycle of study treatment)

Secondary Outcomes (4)

• To assess safety and tolerability

  21 days

• To assess pharmacokinetics (PK)

  The first day of study drug dosing through the sixteenth day of study drug dosing

• To evaluate exploratory biological markers of CUDC-427 activity

  The first day of study drug dosing through the fifteenth day of study drug dosing

• To assess preliminary anti-cancer activity

  3-12 weeks

Study Arms (1)

CUDC-427

EXPERIMENTAL

Drug: CUDC-427

Interventions

CUDC-427 DRUG

CUDC-427 as an oral formulation administered daily on a 14 days on/7 days off schedule

CUDC-427

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Curis, Inc.: lead

Study Sites (2)

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Southern Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2013
• First Posted: July 25, 2013
• Study Start: July 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 1, 2016

Record last verified: 2016-11

Locations

US (2)