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

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

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

Study Overview

• Status: Terminated
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: ME-344; Drug: Topotecan

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, W2 1NY
      • The Bays St Mary's Hospital
    • London, England, United Kingdom, WIG 6AD
      • Sarah Cannon Research Instititute UK
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Pinnacle Oncology Hematology
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
  • Washington
    • Seattle, Washington, United States, 98109
      • University of WA Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ME-344; ME-344 IV, 10 mg/kg on Days 1, 8, 15 and 22 of each 28 day cycle Topotecan IV, 4 mg/m2 on Days 1, 8 and 15 of each 28 day cycle

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.; Other Names: open label; Drug: 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.; Other Names: Hycamtin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: MEI Pharma, Inc.
• Collaborators: SCRI Development Innovations, LLC
• Investigators: Study Director: Richard Ghalie, MD, MEI Pharma, Inc.

Publications and helpful links

Helpful Links

• Sponsor website

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: March 26, 2014
• First Posted (Estimate): March 31, 2014

Study Record Updates

• Last Update Posted (Actual): October 2, 2017
• Last Update Submitted That Met QC Criteria: September 28, 2017
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: ovarian cancer; solid tumors; metastatic; relapsed; refractory; advanced; small cell lung cancer
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Topotecan
• Other Study ID Numbers: ME-344-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO