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

• ClinicalTrials.gov Identifier: NCT02100007
• Recruitment Status: Terminated
• First Posted: March 31, 2014
• Results First Posted: October 2, 2017
• Last Update Posted: October 2, 2017
• Sponsor: MEI Pharma, Inc.
• Collaborator: SCRI Development Innovations, LLC
• Information provided by (Responsible Party): MEI Pharma, Inc.

Study Description

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

Study Design

• 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

Arms and Interventions

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®

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Locations

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

• Study Director: Richard Ghalie, MD; MEI Pharma, Inc.

More Information

Additional Information:

Sponsor website 

• Responsible Party: MEI Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT02100007
• Other Study ID Numbers: ME-344-002
• First Posted: March 31, 2014
• 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:

Neoplasms; Topotecan; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents