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lack of efficacy
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| Name | Class |
|---|---|
| SCRI Development Innovations, LLC | OTHER |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ME-344 | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ME-344 | Drug | 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. |
| 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 |
| 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) |
Not provided
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:
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 any psychiatric disorder or social or geographic situation that would preclude study participation
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| Name | Affiliation | Role |
|---|---|---|
| Richard Ghalie, MD | MEI Pharma, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pinnacle Oncology Hematology | Scottsdale | Arizona | 85258 | United States | ||
| University of Colorado Cancer Center |
Not provided
| Label | URL |
|---|---|
| Sponsor website | View source |
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Fifty-eight (58) potential participants were screened; 46 subjects passed screening and were enrolled in the study.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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: 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The study was conducted in two parts. Fourteen (14) patients enrolled in Part 1 and 32 subjects were enrolled in Part 2.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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: 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Adverse Events | The AE Profile will be determined by the number of AEs regardless of severity | 46 subjects received > 2 doses of ME-344 and topotecan and were eligible for DLT analysis. | Posted | Number | adverse events | Through study completion- an average of 2 years |
|
The occurrence of adverse events was assessed throughout the trial, up to 13 months.
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
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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: 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Procedural Pain | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Vascular disorders | MedDRA 18.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Richard Ghalie, MD, Sr Vice President Clinical Development | MEI Pharma Inc | 858 369-7116 | rghalie@meipharma.com |
Not provided
| ID | Term |
|---|---|
| D012008 | Recurrence |
| D009362 | Neoplasm Metastasis |
| D055752 | Small Cell Lung Carcinoma |
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009385 | Neoplastic Processes |
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| ID | Term |
|---|---|
| C000597890 | ME-344 |
| D019772 | Topotecan |
| ID | Term |
|---|---|
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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|
|
| Topotecan | Drug | 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. |
|
|
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 |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| Oncology Hematology Care | Cincinnati | Ohio | 45242 | United States |
| University of Oklahoma | Oklahoma City | Oklahoma | 73104 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Tennessee Oncology, PLLC | Nashville | Tennessee | 37203 | United States |
| University of WA Seattle Cancer Care Alliance | Seattle | Washington | 98109 | United States |
| The Bays St Mary's Hospital | London | England | W2 1NY | United Kingdom |
| Sarah Cannon Research Instititute UK | London | England | WIG 6AD | United Kingdom |
| Participants |
|
| Age, Continuous | Median | Full Range | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Number of Serious Adverse Events | The SAE Profile will be determined by the number of SAEs | 46 subjects received > 2 doses of ME-344 and topotecan and were eligible for DLT analysis. | Posted | Number | SAEs | Through study completion- an average of 2 years |
|
|
|
| Secondary | Maximum Plasma Concentration (Cmax) | Peak Plasma Concentration (Cmax) of ME-344 in combination with topotecan | 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. | Posted | Mean | Standard Deviation | ng/mL | 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 |
|
|
|
| Secondary | 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. | 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 | Posted | Mean | Full Range | hours | 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 |
|
|
|
| Secondary | Minimum Plasma Concentration (Cmin) of ME-344 | Various pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data. | 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. | Posted | Mean | Standard Deviation | ng/mL | 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 |
|
|
|
| Secondary | Mean Terminal Half-life (t 1/2) | Various pharmacokinetic parameters for ME-344 in plasma were calculated based on the plasma concentration data. | 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. | Posted | Mean | Standard Deviation | hours | 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 |
|
|
|
| Secondary | 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. | Part 1 (N =12), Part 2 (N=29) | Posted | Number | participants | Response was assessed throughout the trial up to 13 months |
|
|
|
| Secondary | Estimate the Overall Survival (OS) | 41 subjects were analysed. Overall survival is defined as the first day of study drug administration to death. | Posted | Median | 95% Confidence Interval | months | Up to 2 years |
|
|
|
| 6 |
| 46 |
| 17 |
| 46 |
| 46 |
| 46 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Fatique | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Gastrointestinal Hemorrhage | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Bacteremia | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Neutropenic sepsis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Muscosal inflammation | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 18.1 | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| QTc Prolonged | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 18.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Muscle weakness | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
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.).
| D009369 | Neoplasms |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |