Clinical trial NCT01544322: Dose Escalation Study of the Safety and Pharmacokinetics of ME-344 Single Agent for Refractory Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: solid tumors
recurrent
advanced
metastatic
refractory
Lead sponsor: MEI Pharma, Inc.
Sponsor class: INDUSTRY
Collaborators: name: SCRI Development Innovations, LLC
First posted: 2012-03-05
Enrollment: 24
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: 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.


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.

Primary outcomes:
measure: Dose limiting toxicity
timeFrame: One Cycle of 28 days
Secondary outcomes:
measure: Response Rate
timeFrame: baseline and a minimum of every 12 weeks
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
Study officials:
affiliation: MEI Pharma, Inc.
name: Robert D Mass, MD
role: STUDY_CHAIR
References: