Clinical trial NCT00852189: Study of EC0489 for the Treatment of Refractory or Metastatic Tumors
Official title: A Phase I Study of EC0489 Administered Weeks 1 and 3 of a 4-Week Cycle
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: Cancer
Phase 1
EC0489
EC20
Refractory
Metastatic
Experimental
Lead sponsor: Endocyte
Sponsor class: INDUSTRY
First posted: 2009-02-26
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: 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 outcomes:
measure: Pharmacokinetic and pharmacodynamic parameters
timeFrame: Obtained during the first cycle of therapy on Days 1 and 3
measure: Anti-tumor activity
timeFrame: Initial dose of study therapy to disease progression
measure: Uptake of 99mTc-EC20 in tumors and normal tissues
timeFrame: 1-2 hours post administration of 99mTc-EC20
measure: Safety and Tolerability
timeFrame: Initiation of study therapy through 30 day post last dose of study therapy
Other outcomes:
Locations:
city: Lafayette
country: United States
facility: Horizon Oncology Center
state: Indiana
city: Baltimore
country: United States
facility: Greenebaum Cancer Center - University of Maryland
state: Maryland
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute - Wayne State University
state: Michigan
city: Lansing
country: United States
facility: Great Lakes Cancer Institute - Michigan State University
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute
state: Michigan
Study officials:
affiliation: Endocyte
name: Richard A Messmann, MD, MHS, MSc
role: STUDY_DIRECTOR
References: