Phase I Dose Escalation Study of the Safety and Pharmacokinetics of ME-143 Single Agent for Refractory Solid Tumors

Solid Tumors Clinical Trial

Official title:

Phase I Open Label Dose Escalation Study of the Safety and Pharmacokinetics of ME-143 as a Single Agent in Patients With Refractory Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01401868
• Other study ID #: ME-143-001
• Status: Completed
• Phase: Phase 1
• First received: July 22, 2011
• Last updated: June 20, 2013
• Start date: September 2011
• Est. completion date: January 2013

Study information

• Verified date: June 2013
• Source: MEI Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the tolerability of ME-143, find the maximum tolerated dose, and the safety profile in patients with refractory solid tumors.

Description:

The purpose of this study is to determine the tolerability of ME-143, find the maximum tolerated dose, dose limiting toxicities, and the safety profile in patients with refractory solid tumors. In addition, the study is planned to characterize the pharmacokinetic profile of ME-143 and describe any clinical anti-tumor activity observed in patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 2013
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

• 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) < or = 2.5 x ULN for the reference laboratory or < 5 x ULN in the presence of liver metastases

• Serum creatinine < or = 1.5 x ULN

• Follicle-Stimulating Hormone (FSH) within normal baseline levels

• Male patients should have a detectable level of testosterone

• Female patients who are known to be capable of conception should have a negative serum pregnancy test (beta-human chorionic gonadotropin ß-hCG]) within 1 week of starting the study.

• All potentially fertile patients will agree to use an effective form of contraception during the study and for 90 days following the last dose of ME-143 (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 carmustine 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 (limited palliative radiation is allowed > 2 weeks), immunotherapy or following major surgery and any surgical incision should be completely healed

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.

• Patients with QTc of > 470 msec on screening ECG. (If a patient has QTc interval >470 msec on screening ECG, the screening ECG may be repeated twice (at least 24 hours apart). The average QTc from the 3 screening ECGs must be <470 msec in order for the patient to be eligible for the study.

• Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed > 2 weeks).

• 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-143 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.

Study Design

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

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• ME-143
experimental drug, dose escalation with 4 dose cohorts of 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. If either the 10 mg/kg or 20 mg/kg dose levels are not tolerable, a 7.5 mg/kg or a 15 mg/kg dose level will be evaluated. 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 per 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.

Locations

Country	Name	City	State
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
MEI Pharma, Inc.	SCRI Development Innovations, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity	Patients will be administered ME-143 IV infusions weekly and assessed by physical exam, vital signs, hematology and clinical chemistry, urinalysis and pharmacokinetic sampling.	within the first 28 day cycle	No
Secondary	Response rate	radiologic assessments will be performed at baseline and a minimum of every 12 weeks	baseline and a minimum of every 12 weeks	No

External Links

•   manuscript
•   Sponsor's web site