Dose Escalation Study of the Safety and Pharmacokinetics of ME-344 Single Agent for Refractory Solid Tumors

NCT ID: NCT01544322

Last Updated: 2015-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2014-08-31

Brief Summary

The purpose of this study is to determine the tolerability of ME-344, find the maximum tolerated dose, and the safety profile in patients with refractory solid tumors.

Conditions

Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

ME-344

experimental drug, dose escalation with 5 planned dose cohorts of 1.2 mg/kg, 2.5 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg; Cycle 1 is 3 weekly IV infusions on Days 1, 8, and 15. After safety assessment, if there is clinical benefit, weekly dosing may continue until withdrawal.

Once the highest tolerated dose has been determined, patients will be enrolled to receive IV infusions 2 days each week. Cycle 1 at the highest dose level is 3 weekly IV infusions on days 1, 2, 8, 9, 15 and 16. After safety assessment, if there is clinical benefit, weekly dosing may continue until withdrawal.

Intervention Type: DRUG

Other Intervention Names

open label; single agent

Eligibility Criteria

Inclusion Criteria

• Provision of informed consent
• Male or female ≥ 18 years of age
• Histologic or cytologic confirmed locally advanced or metastatic cancer that has no standard therapeutic alternatives.
• ECOG Performance status 0-1 (Appendix A)
• A minimum life expectancy of 12 weeks
• Adequate bone marrow, hepatic and renal function as evidenced by:

• Absolute neutrophil count (ANC) > 1.5 x 109/L
• Platelet count > 100 x 109/L
• Hemoglobin > 9.0 g/dL
• Serum bilirubin < 1.5 x ULN
• AST/ALT (SGOT/SGPT) < 2.5 x ULN for the reference laboratory or < 5 x ULN in the presence of liver metastases
• Serum creatinine < 1.5 x ULN
• Adequate cardiac function as evidenced by:

• CK-MB within normal levels at baseline
• Troponin T within normal levels at baseline
• The average QTc from triplicate screening ECGs (every 5 minutes over a total of 15 minutes) must be < 470 msec to be eligible for the study. (If a patient has an average QTc interval >470 msec at screening, the screening ECG may be repeated twice (at least 24 hours apart).
• LV Ejection Fraction > lower limit of institutional normal level
• All potentially fertile patients will agree to use an effective form of contraception during the study and for 30 days following the last dose of ME-344 (an effective form of contraception is defined as an oral contraceptive or a double barrier method).
• At least 4 weeks must have elapsed prior to Day 1 Cycle 1 since prior chemotherapy (6 weeks for nitrosourea or mitomycin C), investigational drug or biologic therapy and any toxicity associated with these treatments has recovered to ≤ NCI-CTCAE Grade 1.
• At least 21 days must have elapsed prior to Day 1 Cycle 1, radiotherapy, immunotherapy or following major surgery and any surgical incision should be completely healed. At least 14 days must have elapsed prior to Day 1 Cycle 1 for "limited palliative radiotherapy", defined as a course of therapy encompassing <25% total bone marrow volume and not exceeding 30 Gy.

Exclusion Criteria

• Patients who are pregnant or breastfeeding
• Tumor involvement of the Central Nervous System (CNS):

• Patients with treated and stable CNS metastases may be eligible to participate after discussion and approval from the Medical Monitor
• Uncontrolled infection or systemic disease.
• Clinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease e.g. angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months.
• Any major surgery, radiotherapy, or immunotherapy within the last 21 days. Limited palliative radiation, defined as encompassing <25% of total bone marrow volume and not exceeding a total dose of 30 Gy, within the last 14 days.
• Chemotherapy regimens with delayed toxicity within the last 4 weeks (or within 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential or delayed toxicity within the last 2 weeks.
• No concurrent systemic chemotherapy or biologic therapy is allowed.
• Known hypersensitivity to any components of ME-344 study drug product.
• Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both).
• History of solid organ transplantation.
• Psychiatric disorder or social or geographic situation that would preclude study participation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SCRI Development Innovations, LLC

OTHER

Sponsor Role: collaborator

MEI Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert D Mass, MD

Role: STUDY_CHAIR

MEI Pharma, Inc.

Locations

Florida Cancer Specialists

Sarasota, Florida, United States

University of Oklahoma

Oklahoma City, Oklahoma, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Countries

United States

Related Links

http://marshalledwardsinc.com

Sponsor's web site

Other Identifiers

ME-344-001

Identifier Type: -

Identifier Source: org_study_id