Study of EC0489 for the Treatment of Refractory or Metastatic Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00852189
Recruitment Status : Completed
First Posted : February 26, 2009
Last Update Posted : August 8, 2012
Information provided by (Responsible Party):

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cancer Drug: EC0489, Injection Drug: EC20 Phase 1

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  (Clinical Trial)
Actual Enrollment : 65 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of EC0489 Administered Weeks 1 and 3 of a 4-Week Cycle
Study Start Date : April 2009
Actual Primary Completion Date : December 2011
Actual Study Completion Date : April 2012

Intervention Details:
  • Drug: EC0489, Injection
    PART A: Dose escalation from a starting dose of 1.0 mg/m2 IV bolus on Monday, Wednesday, and Friday Weeks 1 and 3 of a 4-week cycle to the Maximum Tolerated Dose (MTD)
    Other Name: Folic acid desacetylvinblastine hydrazide conjugate
  • Drug: EC20
    20-25 mCi 99mTc-EC20 administered IV bolus 1-2 hours prior to imaging and at end of study for subjects who received 1 cycle or more of EC0489.
    Other Names:
    • Folic acid-technetium 99m conjugate
    • Folatescan
  • Drug: EC0489, Injection
    PART B: Once PART A MTD is determined, PART B will begin. Dose escalation from a starting dose of 4.2 mg/m2 IV bolus once weekly in a 4-week cycle to the Maximum Tolerated Dose (MTD).
    Other Name: Folic acid desacetylvinblastine hydrazide conjugate

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: 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 :
  1. Pharmacokinetic and pharmacodynamic parameters [ Time Frame: Obtained during the first cycle of therapy on Days 1 and 3 ]
  2. Anti-tumor activity [ Time Frame: Initial dose of study therapy to disease progression ]
  3. Uptake of 99mTc-EC20 in tumors and normal tissues [ Time Frame: 1-2 hours post administration of 99mTc-EC20 ]
  4. Safety and Tolerability [ Time Frame: Initiation of study therapy through 30 day post last dose of study therapy ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00852189

United States, Indiana
Horizon Oncology Center
Lafayette, Indiana, United States, 47905
United States, Maryland
Greenebaum Cancer Center - University of Maryland
Baltimore, Maryland, United States, 21201
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Michigan
Barbara Ann Karmanos Cancer Institute - Wayne State University
Detroit, Michigan, United States, 48201
Great Lakes Cancer Institute - Michigan State University
Lansing, Michigan, United States, 48910
Providence Cancer Institute
Southfield, Michigan, United States, 48075
Sponsors and Collaborators
Study Director: Richard A Messmann, MD, MHS, MSc Endocyte

Responsible Party: Endocyte Identifier: NCT00852189     History of Changes
Other Study ID Numbers: EC-0489-01
First Posted: February 26, 2009    Key Record Dates
Last Update Posted: August 8, 2012
Last Verified: August 2012

Keywords provided by Endocyte:
Phase 1

Additional relevant MeSH terms:
Folic Acid
Vitamin B Complex
Vinca Alkaloids
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action