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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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The purpose of this study is to evaluate the effectiveness of oral topotecan and how well the chemotherapy is tolerated (any side effects) when it is given in different dose levels. The study will also collect information on how the medication is being broken down and absorbed in the body and how quality of life is affected during treatment.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Topotecan | Drug | Topotecan will be received in one of the five dose levels:0.25mg/day,0.5mg/day, 0.75mg/day, 1.0mg/day, and 1.25mg/day. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Single Agent Metronomic Oral Topotecan | The MTD of metronomic oral topotecan was determined using a standard 3+3 dose escalation cohort design. The total sample and the number of subjects who receive each dose in this design depends on the frequency of dose limiting toxicities (DLTs)at each dose level. If 0 out of 3 subjects experience a DLT at a given dose level, 3 subjects will be enrolled at the next higher dose level. If greater than or equal to 2 subjects experience a DLT at a given dose level, dose escalation will be stopped. If 1 out of 3 subjects experience a DLT at a given dose level, 3 subjects are enrolled at the same dose level. | MTD was assessed during the first cycle of treatment (days 1-28). |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Limiting Toxicities (DLT) | DLTs were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. This measure reports the number of subjects who experienced DLT at each dose level during the dose finding portion of the study. | DLTs were assessed during the first cycle of treatment (days 1-28). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Todd D. Tillmanns, M.D. | West Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The West Clinic | Memphis | Tennessee | 38120 | United States |
Informed consent was obtained from all subjects. All subjects underwent a screening period that could last up to 4 weeks during which pre-study assessments were completed. During the dose finding portion of the study, subjects were assigned to a Dose Level during enrollment. Once the MTD was determined, additional subjects were treated at the MTD.
The study was open to enrollment at one community oncology clinic from November 2006 to May 2009.
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| ID | Title | Description |
|---|---|---|
| FG000 | Oral Topotecan 0.25 mg Daily | All subjects in this group were assigned to receive metronomic oral topotecan 0.25 mg daily (Dose Level 1). |
| FG001 | Oral Topotecan 0.50 mg Daily | All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2). |
| FG002 | Oral Topotecan 0.75 mg Daily | All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3). |
| FG003 | Oral Topotecan 1.0 mg Daily | All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4). |
| FG004 | Oral Topotecan 1.25 mg Daily | All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Metronomic Oral Topotecan | All subjects received metronomic oral topotecan daily at the assigned dose level. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| 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 | Maximum Tolerated Dose (MTD) of Single Agent Metronomic Oral Topotecan | The MTD of metronomic oral topotecan was determined using a standard 3+3 dose escalation cohort design. The total sample and the number of subjects who receive each dose in this design depends on the frequency of dose limiting toxicities (DLTs)at each dose level. If 0 out of 3 subjects experience a DLT at a given dose level, 3 subjects will be enrolled at the next higher dose level. If greater than or equal to 2 subjects experience a DLT at a given dose level, dose escalation will be stopped. If 1 out of 3 subjects experience a DLT at a given dose level, 3 subjects are enrolled at the same dose level. | DLT information was available for 3 subjects who received a topotecan dose of 0.25 mg/day, 3 subjects who received a topotecan dose of 0.50 mg/day, 3 subjects who received a topotecan dose of 0.75 mg/day, 3 subjects who received a topotecan dose of 1.0 mg/day, and 2 subjects who received a topotecan dose of 1.25 mg/day. | Posted | Number | mg/day | MTD was assessed during the first cycle of treatment (days 1-28). |
|
Adverse events were collected on day 1 of treatment until one month after the end of study treatment.
Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Oral Topotecan 0.25 mg Daily | All subjects in this group were assigned to receive metronomic oral topotecan 0.25 mg daily (Dose Level 1). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vice President of Scientific Affairs | Accelerated Community Oncology Research Network, Inc. | mwalker@acorncro.com |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D019772 | Topotecan |
| ID | Term |
|---|---|
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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| Best Overall Response |
Best overall response is defined as the best response across all time points. Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of disease progression. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions. |
| Best overall response was assessed after every 8 weeks of treatment and at the end of treatment or time of disease progression, up to 1 year. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 | Metronomic Oral Topotecan | All subjects received metronomic oral topotecan daily at the assigned dose level. |
|
|
| Secondary | Dose Limiting Toxicities (DLT) | DLTs were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. This measure reports the number of subjects who experienced DLT at each dose level during the dose finding portion of the study. | Number of participants analyzed refers to those for whom DLT information was available during the dose finding portion of the study. | Posted | Number | participants | DLTs were assessed during the first cycle of treatment (days 1-28). |
|
|
|
| Secondary | Best Overall Response | Best overall response is defined as the best response across all time points. Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of disease progression. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions. | All enrolled subjects were analyzed for this outcome. | Posted | Number | participants | Best overall response was assessed after every 8 weeks of treatment and at the end of treatment or time of disease progression, up to 1 year. |
|
|
|
| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | Oral Topotecan 0.50 mg Daily | All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2). | 0 | 4 | 4 | 4 |
| EG002 | Oral Topotecan 0.75 mg Daily | All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3). | 0 | 3 | 3 | 3 |
| EG003 | Oral Topotecan 1.0 mg Daily | All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4). | 7 | 14 | 13 | 14 |
| EG004 | Oral Topotecan 1.25 mg Daily | All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5). | 1 | 2 | 2 | 2 |
| Ascites | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Asthenia | General disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Infection | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | CTCAE (3.0) | Non-systematic Assessment |
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| Delirium | Psychiatric disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Vaginal hemorrhage | Reproductive system and breast disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Tachycardia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Eye hemorrhage | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vision blurred | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Abdominal tenderness | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Asthenia | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Chest pain | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Influenza like illness | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Peripheral edema | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pyrexia | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Neutrophil count increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Platelet count increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Waist circumference increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Weight decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Weight increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fluid overload | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Peripheral neuropathy | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Restless leg syndrome | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sinus headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nightmare | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Perineal pain | Reproductive system and breast disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vaginal hemorrhage | Reproductive system and breast disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Exertional dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
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| Partial Response |
|
| Stable Disease |
|
| Progressive Disease |
|
| Not Evaluable |
|