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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02100007
Recruitment Status : Terminated (lack of efficacy)
First Posted : March 31, 2014
Results First Posted : October 2, 2017
Last Update Posted : October 2, 2017
Sponsor:
Collaborator:
SCRI Development Innovations, LLC
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: ME-344 Drug: Topotecan Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : April 2014
Actual Primary Completion Date : January 2016
Actual Study Completion Date : April 2016


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 Name: 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 Name: Hycamtin®




Primary Outcome Measures :
  1. Number of Adverse Events [ Time Frame: Through study completion- an average of 2 years ]
    The AE Profile will be determined by the number of AEs regardless of severity

  2. Number of Serious Adverse Events [ Time Frame: Through study completion- an average of 2 years ]
    The SAE Profile will be determined by the number of SAEs


Secondary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) [ Time Frame: 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

  2. Time to Maximum Plasma Concentration for ME-344 (Tmax) [ Time Frame: 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.

  3. Minimum Plasma Concentration (Cmin) of ME-344 [ Time Frame: 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.

  4. Mean Terminal Half-life (t 1/2) [ Time Frame: 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.

  5. Estimate Overall Response Rate for ME-344 Given in Combination With Topotecan [ Time Frame: 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.

  6. Estimate the Overall Survival (OS) [ Time Frame: Up to 2 years ]
    41 subjects were analysed. Overall survival is defined as the first day of study drug administration to death.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02100007


Locations
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United States, Arizona
Pinnacle Oncology Hematology
Scottsdale, Arizona, United States, 85258
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
United States, Washington
University of WA Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
United Kingdom
The Bays St Mary's Hospital
London, England, United Kingdom, W2 1NY
Sarah Cannon Research Instititute UK
London, England, United Kingdom, WIG 6AD
Sponsors and Collaborators
MEI Pharma, Inc.
SCRI Development Innovations, LLC
Investigators
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Study Director: Richard Ghalie, MD MEI Pharma, Inc.
Additional Information:
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Responsible Party: MEI Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02100007    
Other Study ID Numbers: ME-344-002
First Posted: March 31, 2014    Key Record Dates
Results First Posted: October 2, 2017
Last Update Posted: October 2, 2017
Last Verified: August 2015
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by MEI Pharma, Inc.:
solid tumors
relapsed
advanced
metastatic
small cell lung cancer
ovarian cancer
refractory
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Topotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents