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

Phase 1

Terminated

• Conditions: Solid Tumors
• Interventions: Drug: ME-344; Drug: Topotecan

• Registration Number: NCT02100007
• Lead Sponsor: MEI Pharma, Inc.

Brief 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-03-24
• Study First Submitted QC: 2014-03-26
• Study First Posted: 2014-03-31
• Study Start: 2014-04
• Status Verified: 2015-08
• Primary Completion: 2016-01
• Study Completion: 2016-04
• Results First Submitted: 2017-03-07
• Results First Submitted QC: 2017-09-28
• Last Update Submitted: 2017-09-28
• Results First Posted: 2017-10-02
• Last Update Posted: 2017-10-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 46

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ME-344	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
ME-344	Topotecan	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

Primary Outcome Measures

Name	Time	Method
Number of Serious Adverse Events	Through study completion- an average of 2 years	The SAE Profile will be determined by the number of SAEs
Number of Adverse Events	Through study completion- an average of 2 years	The AE Profile will be determined by the number of AEs regardless of severity

Secondary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration (Cmax)	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	Peak Plasma Concentration (Cmax) of ME-344 in combination with topotecan
Time to Maximum Plasma Concentration for ME-344 (Tmax)	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	Various pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data.
Minimum Plasma Concentration (Cmin) of ME-344	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	Various pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data.
Mean Terminal Half-life (t 1/2)	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	Various pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data.
Estimate Overall Response Rate for ME-344 Given in Combination With Topotecan	Response was assessed throughout the trial up to 13 months	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.
Estimate the Overall Survival (OS)	Up to 2 years	41 subjects were analysed. Overall survival is defined as the first day of study drug administration to death.

Trial Locations

Locations (10)

The Bays St Mary's Hospital; 🇬🇧 London, England, United Kingdom

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Pinnacle Oncology Hematology; 🇺🇸 Scottsdale, Arizona, United States

Oncology Hematology Care; 🇺🇸 Cincinnati, Ohio, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Oklahoma; 🇺🇸 Oklahoma City, Oklahoma, United States

University of WA Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Tennessee Oncology, PLLC; 🇺🇸 Nashville, Tennessee, United States

Sarah Cannon Research Instititute UK; 🇬🇧 London, England, United Kingdom