Study of EC0489 for the Treatment of Refractory or Metastatic Tumors

A Phase I Study of EC0489 Administered Weeks 1 and 3 of a 4-Week Cycle

This is a Phase 1 clinical trial evaluating the safety and tolerability of escalating doses of EC0489 in patients with refractory or metastatic tumors who have exhausted standard therapeutic options.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: EC0489, Injection; Drug: EC20; Drug: EC0489, Injection

Detailed Description

This is a Phase 1, dose escalation study of EC0489 administered by intravenous bolus (IV) during weeks 1 and 3 of a 4-week cycle in PART A and weekly on a 4-week cycle in PART B.

Both Parts are open to patients with refractory or metastatic cancer who have exhausted standard therapeutic options. EC0489 is a drug that is specifically designed to enter cells via a folate vitamin receptor. Experimental evidence shows that the target receptor is over-expressed in many human cancers. There are no previous human studies of EC0489; however, lab research (research in test tubes or animals) using EC0489 has shown activity against tumors in animals. This activity in animal models suggests that EC0489 may be useful as chemotherapy against human cancers. The primary objective of this study is to determine the safety and maximum tolerated dose of EC0489 given by intravenous bolus. The efficacy of treatment will also be measured.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center - University of Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute - Wayne State University
    • Lansing, Michigan, United States, 48910
      • Great Lakes Cancer Institute - Michigan State University
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute

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:

• 18 years of age or older
• Histological or cytological diagnosis of neoplasm
• No effective standard therapeutic options
• ECOG performance status of 0-2
• ≥ 4 weeks post therapeutic radiation or recovered (or returned to baseline) from any acute toxicity associated with prior cytotoxic therapy. Patients previously treated with non-cytotoxic therapy (e.g., EGFR, VGEF, etc.) and who have recovered from or have controlled drug-associated toxicity are allowed to enter the trial after a period consisting of 4 half-lives of the agent.
• Negative serum pregnancy test for women of child-bearing potential within one week prior to treatment with investigational agents (99mTc-EC20 and EC0489)and willingness to practice contraceptive methods
• Adequate bone marrow reserve, renal and hepatic function

Exclusion Criteria:

• Concurrent malignancies
• Women who are pregnant or breast-feeding
• Evidence of symptomatic brain metastases
• Receiving concomitant anticancer therapy (excluding supportive care)
• Requires palliative radiotherapy at time of study entry
• Requires antifolate therapy for comorbid conditions
• Heart failure characterized as greater than NYHA Class I
• History of myocardial infarct
• Any of the following baseline echocardiogram findings: valvular lesions (stenosis or insufficiency) characterized as greater than moderate, systolic ventricular impairment characterized as greater than mild, left ventricular ejection fraction < 55%, any feature of the echocardiogram that would confound interpretation of the serial echocardiograms required by the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose (MTD)	Dose escalation to the highest dose that can be safely administered to produce acceptable, manageable and reversible toxicity in no more than 0 or 1 of 6 patients

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic and pharmacodynamic parameters	Obtained during the first cycle of therapy on Days 1 and 3
Anti-tumor activity	Initial dose of study therapy to disease progression
Uptake of 99mTc-EC20 in tumors and normal tissues	1-2 hours post administration of 99mTc-EC20
Safety and Tolerability	Initiation of study therapy through 30 day post last dose of study therapy

Collaborators and Investigators

• Sponsor: Endocyte
• Investigators: Study Director: Richard A Messmann, MD, MHS, MSc, Endocyte

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: February 25, 2009
• First Submitted That Met QC Criteria: February 25, 2009
• First Posted (Estimate): February 26, 2009

Study Record Updates

• Last Update Posted (Estimate): August 8, 2012
• Last Update Submitted That Met QC Criteria: August 7, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Cancer; Refractory; Phase 1; Metastatic; Experimental; EC20; EC0489
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Micronutrients; Vitamins; Hematinics; Folic Acid; Vitamin B Complex; Vinca Alkaloids
• Other Study ID Numbers: EC-0489-01