A Safety Study of EPC2407, A Anti-Cancer Drug With Vascular Disrupting Activity: In Patients With Advanced Cancer

A First In Man Phase I Study Of EPC2407, A Microtubule Inhibitor Anti-Cancer Drug With Tumor Vascular Endothelial Disrupting Activity: Intravenous Administration Daily For Three Days In Patients With Advanced Solid Tumors And Lymphomas

This study will evaluate the safety, pharmacokinetics (PK), and pharmacodynamic effects of a novel anti-cancer drug, EPC2407, administered to patients with advanced cancer which have not responded to or have recurred following treatment with available therapies

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: EPC2407 (crinobulin)

Detailed Description

This is a Phase I, open label, multicenter, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of EPC2407 administered intravenously over 60 minutes on a QDx3 schedule repeated every 21 days. Patients are enrolled and dosed at the level defined by the escalation scheme. The primary goal of the study design is to assess toxicity at the fixed dose levels according to the modified Fibonacci schema.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Healthcare
  • California
    • Beverly Hills, California, United States, 90211
      • Tower Oncology Research
    • San Diego, California, United States, 92093
      • Rebecca and John Moores UCSD Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed solid tumor or lymphoma,which has progressed on standard therapies, for which effective therapy is not available or for patients who are unwilling to undergo such therapies.
2. Males and Females at least 18 years of age

3. Laboratory data as specified below (according to the site's clinical laboratory ranges for normal):

   i. Hematology: ANC >1500 cells/mm3, platelet count >100,000 cells/mm3 and Hemoglobin > 9 gm/L ii. Hepatic: Direct bilirubin <1.5 X ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 X ULN. For patients with known liver metastases or liver neoplasms: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5.0 X ULN iii. Renal: serum creatinine WNL or creatinine clearance >60 mL/min

4. 12-lead electrocardiogram (ECG) QT intervals: QTc ≤ 450 msec for men and ≤ 470 msec for women.
5. Estimated life expectancy of at least 3 months
6. ECOG Performance Status < or = 1
7. Previously treated CNS disease allowed if treatment completed and stable for 4 weeks.
8. For men and women of child-producing potential - willingness to employ appropriate contraceptive methods (including abstinence) during the study
9. Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments
10. Cardiac ejection fraction ≥50% by 2D Echocardiogram or > institutional lower limits of normal

Exclusion Criteria:

1. Women who are pregnant or nursing
2. Radiotherapy or any chemotherapy within the previous 21 days or five half lives of prior drug (whichever is shorter). See also exclusion #4 below for patients at risk for cardiac toxicity. Recovery to Grade 1 or less from chemotherapy-induced toxic effect, except alopecia, is required.
3. Major surgery within the last 4 weeks or minor surgery within the last 2 weeks
4. Significant risk of cardiac drug toxicity due to any of the following: a) Active New York Heart Association Class III or IV, b) history of or current congestive heart failure, c) history of myocardial infarction within the last 6 months or ongoing unstable angina, or anthracycline exposure per exclusion #5.
5. Anthracycline exposure exceeding a cumulative dose of 360 mg/m²
6. Known and ongoing HIV, Hepatitis B or Hepatitis C infection
7. Concomitant use of strong inhibitors of the liver microsomal enzymes CYP2C8, CYP2C9, CYP2C19 and CYP3A4.
8. Participation in concurrent study of an investigational agent or device
9. Any other condition including but not limited to major co-morbidities, which in the opinion of the investigator would render the patient ineligible
10. O2 Saturation by pulse oximetry at rest < 90%
11. Concomitant use of drugs that have significant risk of Torsades de Pointes will also be prohibited. Please refer to drugs listed under "Drugs with Risk of Torsades de Pointes"

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: EPC2407 (crinobulin)	Drug: EPC2407 (crinobulin); IV infusion 1 to 4 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety	Duration of drug exposure

Collaborators and Investigators

• Sponsor: EpiCept Corporation

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (ACTUAL): April 1, 2009
• Study Completion (ACTUAL): September 1, 2009

Study Registration Dates

• First Submitted: January 16, 2007
• First Submitted That Met QC Criteria: January 16, 2007
• First Posted (ESTIMATE): January 18, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): September 10, 2009
• Last Update Submitted That Met QC Criteria: September 9, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Cancer; Lymphoma; Tumor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: EPC2006-04