Dose Escalation Study of the Safety and Pharmacokinetics of ME-344 Single Agent for Refractory Solid Tumors (ME-344-001)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
SCRI Development Innovations, LLC
Information provided by (Responsible Party):
MEI Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01544322
First received: February 22, 2012
Last updated: April 18, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Solid Tumors
Drug: ME-344
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Open Label Dose Escalation Study of the Safety and Pharmacokinetics of ME-344 as a Single Agent in Patients With Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by MEI Pharma, Inc.:

Primary Outcome Measures:
  • Dose limiting toxicity [ Time Frame: One Cycle of 28 days ] [ Designated as safety issue: Yes ]
    Patients will be administered ME-344 IV infusions weekly for 3 weeks during the first 28 days cycle for dose limiting toxicity. Patients will be assessed by physical exam, vital signs, hematology and clinical chemistry, urinalysis, ECG, echocardiogram and pharmacokinetic sampling.


Secondary Outcome Measures:
  • Response Rate [ Time Frame: baseline and a minimum of every 12 weeks ] [ Designated as safety issue: No ]
    Radiologic assessments will be performed at baseline and a minimum of every 12 weeks. Patients may continue weekly dosing if there is clinical beneficial determined by the Investigator.


Estimated Enrollment: 24
Study Start Date: May 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 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.

    Other Names:
    • open label
    • single agent
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01544322

Locations
United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 73104
Sponsors and Collaborators
MEI Pharma, Inc.
SCRI Development Innovations, LLC
Investigators
Study Chair: Robert D Mass, MD MEI Pharma, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: MEI Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01544322     History of Changes
Other Study ID Numbers: ME-344-001
Study First Received: February 22, 2012
Last Updated: April 18, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by MEI Pharma, Inc.:
solid tumors
recurrent
advanced
metastatic
refractory

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 01, 2014