Study of EC0489 for the Treatment of Refractory or Metastatic Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Endocyte
ClinicalTrials.gov Identifier:
NCT00852189
First received: February 25, 2009
Last updated: August 7, 2012
Last verified: August 2012
  Purpose

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 Intervention Phase
Cancer
Drug: EC0489, Injection
Drug: EC20
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of EC0489 Administered Weeks 1 and 3 of a 4-Week Cycle

Resource links provided by NLM:


Further study details as provided by Endocyte:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic and pharmacodynamic parameters [ Time Frame: Obtained during the first cycle of therapy on Days 1 and 3 ] [ Designated as safety issue: No ]
  • Anti-tumor activity [ Time Frame: Initial dose of study therapy to disease progression ] [ Designated as safety issue: No ]
  • Uptake of 99mTc-EC20 in tumors and normal tissues [ Time Frame: 1-2 hours post administration of 99mTc-EC20 ] [ Designated as safety issue: No ]
  • Safety and Tolerability [ Time Frame: Initiation of study therapy through 30 day post last dose of study therapy ] [ Designated as safety issue: Yes ]

Enrollment: 65
Study Start Date: April 2009
Study Completion Date: April 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
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
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00852189

Locations
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
Endocyte
Investigators
Study Director: Richard A Messmann, MD, MHS, MSc Endocyte
  More Information

No publications provided

Responsible Party: Endocyte
ClinicalTrials.gov Identifier: NCT00852189     History of Changes
Other Study ID Numbers: EC-0489-01
Study First Received: February 25, 2009
Last Updated: August 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Endocyte:
Cancer
Phase 1
EC0489
EC20
Refractory
Metastatic
Experimental

Additional relevant MeSH terms:
Folic Acid
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014