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Study of EC0489 for the Treatment of Refractory or Metastatic Tumors

Phase 1
Completed
Conditions
Cancer
Registration Number
NCT00852189
Lead Sponsor
Endocyte
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
65
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Pharmacokinetic and pharmacodynamic parametersObtained during the first cycle of therapy on Days 1 and 3
Anti-tumor activityInitial dose of study therapy to disease progression
Uptake of 99mTc-EC20 in tumors and normal tissues1-2 hours post administration of 99mTc-EC20
Safety and TolerabilityInitiation of study therapy through 30 day post last dose of study therapy

Trial Locations

Locations (6)

Horizon Oncology Center

🇺🇸

Lafayette, Indiana, United States

Greenebaum Cancer Center - University of Maryland

🇺🇸

Baltimore, Maryland, United States

Center for Cancer and Blood Disorders

🇺🇸

Bethesda, Maryland, United States

Barbara Ann Karmanos Cancer Institute - Wayne State University

🇺🇸

Detroit, Michigan, United States

Great Lakes Cancer Institute - Michigan State University

🇺🇸

Lansing, Michigan, United States

Providence Cancer Institute

🇺🇸

Southfield, Michigan, United States

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