A Phase I Study to Assess the Safety, Pharmacokinetics, and Potential Effects of Amrubicin on the QT/QTc Interval in Cancer Patients With Advanced Solid Tumors.

NCT00915083 | Completed Phase 1

• 1 other identifier: AMR PH US 2008 PK002
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of the study is to determine whether amrubicin is safe and effective in the treatment of patients with advanced solid tumors. The study will assess the pharmacokinetics of the amrubicin and if it has an effect on the heart.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (3)

• To characterize the pharmacokinetics of amrubicin and amrubicinol (metabolite) in plasma, whole blood, and urine in patients given amrubicin as 5 minute IV infusions at 40 mg/m2 for 3 consecutive days; data will be obtained from blood & urine samples

  The duration of making measurements during the first cycle is 21 days. All data relating to the primary outcome measure is collected during this time. There is an optional Extension Phase during which subjects can continue to receive additional 21-day cycles of amrubicin unless there is evidence of tumor progression or unacceptable toxicity. The duration of measurements depends on how long the subject continues on treatment.

  Cycle 1: all primary outcome measures are collected during the first 21 days.

• To evaluate the potential effects on the QT/QTc interval in cancer patients when treated with 5 minute IV infusions of amrubicin 40 mg/m2 daily for 3 consecutive days; data will be obtained by ECG extraction from continuous 12-lead Holter monitoring

  The duration of making measurements during the first cycle is 21 days. All data relating to the primary outcome measure is collected during this time. There is an optional Extension Phase during which subjects can continue to receive additional 21-day cycles of amrubicin unless there is evidence of tumor progression or unacceptable toxicity. The duration of measurements depends on how long the subject continues on treatment.

  Cycle 1: all primary outcome measures are collected during the first 21 days.

• To determine the safety and tolerability of 40 mg/m2 amrubicin given as 5 minute IV infusions for 3 consecutive days; information will be collected by adverse event monitoring and laboratory safety tests.

  The duration of making measurements during the first cycle is 21 days. All data relating to the primary outcome measure is collected during this time. There is an optional Extension Phase during which subjects can continue to receive additional 21-day cycles of amrubicin unless there is evidence of tumor progression or unacceptable toxicity. The duration of measurements depends on how long the subject continues on treatment.

  Cycle 1: all primary outcome measures are collected during the first 21 days.

Secondary Outcomes (1)

• 1. Explore the relationship between pharmacokinetics and QTc interval change. Information will be obtained by further analysis of the datasets obtained from the primary outcome measures

  Cycle 1: all primary outcome measures are collected during the first 21 days.

Study Arms (1)

Amrubicin 40mg/m^2

EXPERIMENTAL

Amrubicin 40mg/m\^2 given as a 5 minute IV infusion on Days 1, 2 \& 3 of a 21 day cycle

Drug: Amrubicin

Interventions

Amrubicin DRUG

40mg/m\^2 5 minute IV infusion for 3 consecutive days (21 day cycle)

Amrubicin 40mg/m^2

Eligibility Criteria

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

You may qualify if:

• Patients meeting all of the following criteria will be considered for enrollment into the study:
• Males or females, aged 18-65 years;
• Histological or cytological diagnosis of solid malignancy for which no acceptable standard therapy exists or for which approved standard therapy has failed;
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
• Life expectancy greater than 3 months;
• Nonsmoker or not smoked or used tobacco products for at least 3 months before the screening visit and agree to abstain from smoking/using tobacco products throughout the formal study and until the End of Study visit;
• Capable of giving informed consent, has signed the informed consent form, and is willing to comply with scheduled visits, dose administration, and other study procedures;
• Women of childbearing potential may participate, providing they have a negative serum pregnancy test (β-HCG) at screening, and a negative urine pregnancy test prior to dosing on Day 1 of each cycle;
• Males and females of childbearing potential must agree to the use of at least 2 effective contraceptive methods until at least 28 days following the last dose of study drug;
• Serum potassium, magnesium and corrected calcium that is within institutional normal range at screening;
• Adequate organ function including the following:
• Adequate bone marrow reserve: absolute neutrophil count (segmented and bands) (ANC) ≥1.5 x 109/L, platelet count ≥100 x 109/L, and hemoglobin ≥90 g/L,
• Hepatic: bilirubin ≤1.5 x the upper limit of normal (ULN), ALT and AST ≤2.0 x ULN,
• Renal: serum creatinine ≤1.5 x ULN or calculated creatinine clearance \>80 mL/min.

You may not qualify if:

• Patients meeting any of the following criteria will be excluded from the study:
• Hypersensitivity to amrubicin or related compounds;
• Radiotherapy with curative intent to a primary disease complex ≤ 28 days before first dose; cranial radiotherapy ≤ 21 days before first dose; radiotherapy to all other areas ≤ 7 days before first dose of amrubicin;
• History or presence of clinically significant abnormal 12-lead ECG or triplicate ECGs with a mean QT interval corrected for heart rate (HR) using Fridericia's method (QTcF) of \>450 msec (males) or \>470 msec (females), a PR interval \>240 msec or a QRS interval \>110 msec (within 3 months of screening visit);
• Left ventricular ejection fraction (LVEF) \<50%;
• Recent history (within 3 months of screening visit) of pericarditis and pericardial effusion;
• History within 6 months of the screening visit of one of the following:
• cardiac disease including congenital long-QT syndrome,
• angina, congestive heart failure,
• myocardial ischemia or infarction,
• myocarditis, chest pain or dyspnea on exertion of cardiac origin,,
• idiopathic or hypertrophic cardiomyopathy,
• sarcoidosis,
• syncope,
• epilepsy,

Sponsors & Collaborators

• Celgene: lead

Study Sites (8)

University of California San Diego

La Jolla, California, 92093, United States

Location

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Indiana University Cancer Pavilion

Indianapolis, Indiana, 46202, United States

Location

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Sinai Hospital of Baltimore- Alvin and Lois Lapidus Cancer Institute

Baltimore, Maryland, 21215, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

UT Health Science Center at San Antonio- Cancer Therapy and Research Center

San Antonio, Texas, 78229, United States

Location

Hunstman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Chen N, et al. Phase I study to assess pharmacokinetics (PK), QT/QTc effect, and safety of amrubicin in patients (pts) with advanced solid tumors. Presented at 2011 ASCO Annual Meeting, June 3-7, 2011, Chicaco, IL. Abstract No. 7073 N

  BACKGROUND

MeSH Terms

Interventions

amrubicin

Study Officials

• Markus Renschler, MD

  Celgene Corporation

  STUDY DIRECTOR

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: June 4, 2009
• First Posted: June 5, 2009
• Study Start: June 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: November 1, 2019

Record last verified: 2019-10

Locations

US (8)