Study of EC0489 for the Treatment of Refractory or Metastatic Tumors

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00852189
• Other study ID #: EC-0489-01
• Status: Completed
• Phase: Phase 1
• First received: February 25, 2009
• Last updated: August 7, 2012
• Start date: April 2009
• Est. completion date: April 2012

Study information

• Verified date: August 2012
• Source: Endocyte
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: April 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

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)
• 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.
• 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).

Locations

Country	Name	City	State
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	Horizon Oncology Center	Lafayette	Indiana
United States	Great Lakes Cancer Institute - Michigan State University	Lansing	Michigan
United States	Providence Cancer Institute	Southfield	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Endocyte

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Pharmacokinetic and pharmacodynamic parameters		Obtained during the first cycle of therapy on Days 1 and 3	No
Secondary	Anti-tumor activity		Initial dose of study therapy to disease progression	No
Secondary	Uptake of 99mTc-EC20 in tumors and normal tissues		1-2 hours post administration of 99mTc-EC20	No
Secondary	Safety and Tolerability		Initiation of study therapy through 30 day post last dose of study therapy	Yes