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.

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.

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