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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.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Solid Tumors
Interventions Drug: ME-344
Drug: Topotecan
Enrollment 46
Recruitment Details This study was open to recruitment from April 30, 2014 through December 7, 2015 at 7 investigational sites in the USA and 2 sites in the United Kingdom. Forty-six patients were enrolled. The study was conducted in two parts. Fourteen (14) patients enrolled in Part 1 and 32 subjects were enrolled in Part 2.
Pre-assignment Details Fifty-eight (58) potential participants were screened; 46 subjects passed screening and were enrolled in the study.
Arm/Group Title ME-344
Hide Arm/Group Description

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: 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.

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.

Period Title: Overall Study
Started 46
Completed 46
Not Completed 0
Arm/Group Title ME-344
Hide Arm/Group Description

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: 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.

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.

Overall Number of Baseline Participants 46
Hide Baseline Analysis Population Description
The study was conducted in two parts. Fourteen (14) patients enrolled in Part 1 and 32 subjects were enrolled in Part 2.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 46 participants
<=18 years
0
   0.0%
Between 18 and 65 years
34
  73.9%
>=65 years
12
  26.1%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 46 participants
59.5
(26 to 78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 46 participants
Female
40
  87.0%
Male
6
  13.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 46 participants
Hispanic or Latino
3
   6.5%
Not Hispanic or Latino
41
  89.1%
Unknown or Not Reported
2
   4.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 46 participants
White
42
  91.3%
Black or African American
1
   2.2%
Asian
2
   4.3%
Other
1
   2.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 46 participants
United States 38
United Kingdom 8
1.Primary Outcome
Title Number of Adverse Events
Hide Description The AE Profile will be determined by the number of AEs regardless of severity
Time Frame Through study completion- an average of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
46 subjects received > 2 doses of ME-344 and topotecan and were eligible for DLT analysis.
Arm/Group Title ME-344
Hide Arm/Group Description:

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: 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.

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.

Overall Number of Participants Analyzed 46
Measure Type: Number
Unit of Measure: adverse events
595
2.Primary Outcome
Title Number of Serious Adverse Events
Hide Description The SAE Profile will be determined by the number of SAEs
Time Frame Through study completion- an average of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
46 subjects received > 2 doses of ME-344 and topotecan and were eligible for DLT analysis.
Arm/Group Title ME-344
Hide Arm/Group Description:
ME-344 IV, 10 mg/kg on Days 1, 8, 15 and 22 of each 28 day cycle ...
Overall Number of Participants Analyzed 46
Measure Type: Number
Unit of Measure: SAEs
23
3.Secondary Outcome
Title Maximum Plasma Concentration (Cmax)
Hide Description Peak Plasma Concentration (Cmax) of ME-344 in combination with topotecan
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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data from 13 patients who received treatment in Part 1 of the study.
Arm/Group Title ME-344
Hide Arm/Group Description:

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: 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.

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.

Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ng/mL
20880  (8201.3)
4.Secondary Outcome
Title Time to Maximum Plasma Concentration for ME-344 (Tmax)
Hide Description Various pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data.
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
Hide Outcome Measure Data
Hide Analysis Population Description
Samples were collected from patients in Part 1 of the study for measurement of plasma concentration of ME-344. Samples were collected from 13 patients in Part 1
Arm/Group Title ME-344
Hide Arm/Group Description:

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: 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.

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.

Overall Number of Participants Analyzed 13
Mean (Full Range)
Unit of Measure: hours
0.5
(0.48 to 2.02)
5.Secondary Outcome
Title Minimum Plasma Concentration (Cmin) of ME-344
Hide Description Various pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data.
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
Hide Outcome Measure Data
Hide Analysis Population Description
Samples were collected from patients in Part 1 of the study for measurement of plasma concentration of ME-344. Samples were collected from 13 patients in Part 1.
Arm/Group Title ME-344
Hide Arm/Group Description:

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: 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.

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.

Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: ng/mL
25.3  (12.824)
6.Secondary Outcome
Title Mean Terminal Half-life (t 1/2)
Hide Description Various pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data.
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
Hide Outcome Measure Data
Hide Analysis Population Description
Samples were collected from patients in Part 1 of the study for measurement of plasma concentration of ME-344. Samples were collected from 13 patients in Part 1.
Arm/Group Title ME-344
Hide Arm/Group Description:

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: 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.

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.

Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: hours
5.301  (2.0114)
7.Secondary Outcome
Title Estimate Overall Response Rate for ME-344 Given in Combination With Topotecan
Hide Description 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.
Time Frame Response was assessed throughout the trial up to 13 months
Hide Outcome Measure Data
Hide Analysis Population Description
Part 1 (N =12), Part 2 (N=29)
Arm/Group Title ME-344
Hide Arm/Group Description:

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: 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.

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.

Overall Number of Participants Analyzed 41
Measure Type: Number
Unit of Measure: participants
1
8.Secondary Outcome
Title Estimate the Overall Survival (OS)
Hide Description 41 subjects were analysed. Overall survival is defined as the first day of study drug administration to death.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ME-344
Hide Arm/Group Description:

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: 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.

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.

Overall Number of Participants Analyzed 41
Median (95% Confidence Interval)
Unit of Measure: months
3.7
(2.8 to 5.4)
Time Frame The occurrence of adverse events was assessed throughout the trial, up to 13 months.
Adverse Event Reporting Description Forty-six patients were enrolled in the trial and were to receive both ME-344 and topotecan. Forty-five subjects received both drugs, 1 subject received only ME-344
 
Arm/Group Title ME-344
Hide Arm/Group Description

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: 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.

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.

All-Cause Mortality
ME-344
Affected / at Risk (%)
Total   6/46 (13.04%)    
Show Serious Adverse Events Hide Serious Adverse Events
ME-344
Affected / at Risk (%) # Events
Total   17/46 (36.96%)    
Blood and lymphatic system disorders   
Febrile Neutropenia  1  2/46 (4.35%)  2
Thrombocytopenia  1  2/46 (4.35%)  2
Gastrointestinal disorders   
Diarrhea  1  1/46 (2.17%)  1
Gastrointestinal Hemorrhage  1  1/46 (2.17%)  1
Intestinal obstruction  1  1/46 (2.17%)  1
Small intestinal obstruction  1  3/46 (6.52%)  3
Abdominal Pain  1  1/46 (2.17%)  1
General disorders   
Fatique  1  1/46 (2.17%)  1
Infections and infestations   
Bacteremia  1  1/46 (2.17%)  1
Neutropenic sepsis  1  1/46 (2.17%)  2
Pneumonia  1  1/46 (2.17%)  1
Sepsis  1  1/46 (2.17%)  1
Urinary tract infection  1  1/46 (2.17%)  1
Injury, poisoning and procedural complications   
Procedural Pain  1  1/46 (2.17%)  1
Metabolism and nutrition disorders   
Diabetic ketoacidosis  1  1/46 (2.17%)  1
Musculoskeletal and connective tissue disorders   
Muscular weakness  1  1/46 (2.17%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  1/46 (2.17%)  2
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ME-344
Affected / at Risk (%) # Events
Total   46/46 (100.00%)    
Blood and lymphatic system disorders   
Neutropenia  1  21/46 (45.65%)  45
Thrombocytopenia  1  18/46 (39.13%)  33
Anaemia  1  16/46 (34.78%)  31
Gastrointestinal disorders   
Nausea  1  22/46 (47.83%)  34
Diarrhoea  1  21/46 (45.65%)  25
Vomiting  1  18/46 (39.13%)  29
Constipation  1  15/46 (32.61%)  19
Abdominal pain  1  7/46 (15.22%)  12
Abdominal pain lower  1  3/46 (6.52%)  3
Dyspepsia  1  3/46 (6.52%)  3
Gastrooesophageal reflux disease  1  3/46 (6.52%)  3
General disorders   
Fatigue  1  30/46 (65.22%)  42
Asthenia  1  7/46 (15.22%)  11
Chest pain  1  6/46 (13.04%)  10
Chest discomfort  1  5/46 (10.87%)  7
Muscosal inflammation  1  3/46 (6.52%)  5
Oedema peripheral  1  3/46 (6.52%)  3
Peripheral swelling  1  3/46 (6.52%)  3
Pyrexia  1  3/46 (6.52%)  4
Infections and infestations   
Urinary tract infection  1  5/46 (10.87%)  5
Upper Respiratory Tract Infection  1  4/46 (8.70%)  4
Injury, poisoning and procedural complications   
Infusion related reaction  1  4/46 (8.70%)  6
Investigations   
Weight decreased  1  9/46 (19.57%)  12
White blood cell count decreased  1  6/46 (13.04%)  13
Neutrophil count decreased  1  5/46 (10.87%)  11
Platelet count decreased  1  5/46 (10.87%)  25
QTc Prolonged  1  3/46 (6.52%)  3
Metabolism and nutrition disorders   
Decreased appetite  1  19/46 (41.30%)  20
Hypokalemia  1  6/46 (13.04%)  24
Dehydration  1  4/46 (8.70%)  4
Hypomagnesaemia  1  3/46 (6.52%)  4
Hyponatremia  1  3/46 (6.52%)  5
Musculoskeletal and connective tissue disorders   
Arthralgia  1  8/46 (17.39%)  10
Back pain  1  8/46 (17.39%)  8
Muscle spasms  1  5/46 (10.87%)  6
Muscle weakness  1  3/46 (6.52%)  3
Myalgia  1  3/46 (6.52%)  5
Pain in extremity  1  3/46 (6.52%)  3
Nervous system disorders   
Headache  1  6/46 (13.04%)  6
Dizziness  1  5/46 (10.87%)  5
Paraesthesia  1  4/46 (8.70%)  5
Psychiatric disorders   
Anxiety  1  3/46 (6.52%)  3
Renal and urinary disorders   
Dysuria  1  3/46 (6.52%)  3
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  8/46 (17.39%)  9
Cough  1  7/46 (15.22%)  7
Oropharyngeal pain  1  3/46 (6.52%)  4
Productive cough  1  3/46 (6.52%)  3
Skin and subcutaneous tissue disorders   
Alopecia  1  4/46 (8.70%)  4
Dry skin  1  3/46 (6.52%)  3
Vascular disorders   
Hypertension  1  19/46 (41.30%)  27
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Each PI has a CDA in place that restricts them from discussing the results of the clinical study at a scientific meeting or any other public or private forum or to publish in a scientific or academic journal the results of the clinical study without the approval of the Sponsor Company (MEI Pharma Inc.).
Results Point of Contact
Name/Title: Richard Ghalie, MD, Sr Vice President Clinical Development
Organization: MEI Pharma Inc
Phone: 858 369-7116
Responsible Party: MEI Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02100007     History of Changes
Other Study ID Numbers: ME-344-002
First Submitted: March 24, 2014
First Posted: March 31, 2014
Results First Submitted: March 7, 2017
Results First Posted: October 2, 2017
Last Update Posted: October 2, 2017