ME-344 Given in Combination With Hycamtin® in Patients With Solid Tumors

Solid Tumors Clinical Trial

Official title:

A Phase Ib Open Label Study of the Safety and Tolerability of ME-344 Given in Combination With Topotecan (Hycamtin®) in Patients With Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02100007
• Other study ID #: ME-344-002
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: March 24, 2014
• Last updated: September 28, 2017
• Start date: April 2014
• Est. completion date: April 2016

Study information

• Verified date: August 2015
• Source: MEI Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and tolerability of ME-344 when given in combination with Hycamtin® in patients with solid tumors

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 46
• Est. completion date: April 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologic or cytologic confirmed locally advanced or metastatic small cell lung cancer, ovarian cancer, or cervical cancer (Part 1); small cell lung cancer and ovarian cancer (Part 2)

• Patients with ovarian and small cell lung cancer must have failed initial therapy

• Patients with carcinoma of the cervix must have advanced disease not amenable to curative surgery and/or radiation therapy

• Patients may not have received more than 4 prior regimens of therapy

• Patients may not previously have received irinotecan, topotecan or other topoisomerase I inhibitor

• ECOG Performance status 0-1 (Appendix B)

• 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 or creatinine clearance = 60 mL/min as measured by institutional standards

• At least 21 days must have elapsed prior to Day 1 Cycle 1, since any radiotherapy, immunotherapy or following major surgery; any surgical incision should be completely healed. At least 14 days must have elapsed prior to Day 1 Cycle 1 since "limited palliative radiotherapy", defined as a course of therapy encompassing <25% total bone marrow volume and not exceeding 30 GY.

Exclusion Criteria:

• Patients with tumor involvement of the Central Nervous System (CNS). SCLC patients with previously treated CNS lesions must have stable CNS disease for at least 4 weeks

• Patients with uncontrolled infection or systemic disease

• Patients with 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 who have toxicity from last prior therapy that has not recovered to at least Grade 1, with the exception of Grade 2 alopecia

• Patients who have had any chemotherapy regimens, biologic, or targeted therapies within the 2 weeks prior to Cycle 1 Day 1

• Patients with any neuropathy > Grade 1

• Patients with known hypersensitivity to any components of ME-344 or topotecan study drug product

• Patients with known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)

• Patients with a history of solid organ transplantation

• Patients with presence of concurrent or active malignant disease (other than disease under study) within the last 12 months with the exception of adequately treated in-situ carcinomas, basal or squamous cell carcinoma, or non-melanomatous skin cancer.

Patients with any psychiatric disorder or social or geographic situation that would preclude study participation

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• ME-344
Part 1: ME-344 IV at 10 mg/kg on Days 1, 8, 15, and 22 of each 28-day cycle. Part 2: ME-344 IV at the dose defined in Part 1 on Days 1, 8, 15, and 22 of each 28 day cycle. Patients will be allowed to continue receiving ME-344 infusions weekly according to the assigned dose level as long as there is clinical benefit to the patient as assessed by the Investigator.
• Topotecan
Part 1: Topotecan 4 mg/m2 i.v. weekly on Days 1, 8 and 15 of each 28-day cycle. Part 2: Topotecan 4 mg/m2 i.v. weekly on Days 1, 8 and 15 of each 28-day cycle.

Locations

Country	Name	City	State
United Kingdom	Sarah Cannon Research Instititute UK	London	England
United Kingdom	The Bays St Mary's Hospital	London	England
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Pinnacle Oncology Hematology	Scottsdale	Arizona
United States	University of WA Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Adverse Events	The AE Profile will be determined by the number of AEs regardless of severity	Through study completion- an average of 2 years
Primary	Number of Serious Adverse Events	The SAE Profile will be determined by the number of SAEs	Through study completion- an average of 2 years
Secondary	Maximum Plasma Concentration (Cmax)	Peak Plasma Concentration (Cmax) of ME-344 in combination with topotecan	Cycle 1 Day 1, at 0, .5, 1, 2, 4, 6 and 24 hours post-dose and Day 15 at 0 and end of infusion
Secondary	Time to Maximum Plasma Concentration for ME-344 (Tmax)	Various pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data.	Cycle 1 Day 1, at 0, .5, 1, 2, 4, 6 and 24 hours post-dose and Day 15 at 0 and end of infusion
Secondary	Minimum Plasma Concentration (Cmin) of ME-344	Various pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data.	Cycle 1 Day 1, at 0, .5, 1, 2, 4, 6 and 24 hours post-dose and Day 15 at 0 and end of infusion
Secondary	Mean Terminal Half-life (t 1/2)	Various pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data.	Cycle 1 Day 1, at 0, .5, 1, 2, 4, 6 and 24 hours post-dose and Day 15 at 0 and end of infusion
Secondary	Estimate Overall Response Rate for ME-344 Given in Combination With Topotecan	Overall response rate was defined as the total number of patients with Complete Response plus Partial Response. All efficacy assessments were to include a baseline assessment and follow-up assessments at a minimum of every 8 weeks for the first 6 cycles, then every 12 weeks thereafter, while receiving study drug. Tumor response and progression-free survival were assessed using RECIST 1.1 criteria or GCIG criteria for CA-125 levels.	Response was assessed throughout the trial up to 13 months
Secondary	Estimate the Overall Survival (OS)	41 subjects were analysed. Overall survival is defined as the first day of study drug administration to death.	Up to 2 years

External Links

•   Sponsor website