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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: ME-344
* Drug: Topotecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ME-344<br>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<br>* 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.<br>* Other names: open label;Drug: Topotecan<br>* 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.<br>* Other names: Hycamtin®;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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solid tumors, relapsed, advanced, metastatic, small cell lung cancer, ovarian cancer, refractory