Endometrial Cancer, Neoplasms, Endometrial
Conditions
Keywords
Hycamtin, endometrial cancer, topotecan
Brief summary
The purpose of this study is to find out if Hycamtin given weekly is safe and effective for treating your endometrial cancer.
Interventions
DRUGtopotecan
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A subject will be eligible for inclusion in this study only if all of the following criteria are met: * Subject has provided a written informed consent. * Subject must be female and ≥18 years of age. * Subjects' original endometrial carcinoma (any histologic type) must have had pathologic confirmation. * Subject must have recurrent or persistent endometrial cancer. * Subject must have at least one measurable lesion according to GOG-modified RECIST criteria. * Measurable disease must be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation, plain X-ray, CT and MRI, or ≥10 mm when measured by spiral CT. * Measurable disease found on chest X-ray must be confirmed with CT or MRI. Either CT or MRI must be used throughout the study to further evaluate these lesions. * The same diagnostic method (CT, MRI, X-ray or physical exam) used to evaluate disease, must be used throughout the study to consistently evaluate lesions. * Palpable tumor masses that cannot be evaluated by CT or MRI scan should be evaluated by ultrasound or confirmed by biopsy. * Evaluable disease (measurable or non-measurable) may be in a field of prior radiation provided that at least six weeks have elapsed since receiving radiation and disease progression is clearly documented by radiographic study. It is preferential for the target lesion to be located outside an irradiated field. * Non-measurable disease is defined as all other lesions, including small lesions (longest diameter \<20 mm with conventional techniques or \<10 mm with spiral CT scan). * Subject has received one prior chemotherapy regimen (excluding all topoisomerase I inhibitors e.g., HYCAMTIN and irinotecan). * Subject is allowed to have received, but is not required to have received, one additional prior non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition: Non-cytotoxic (biologic or cytostatic) agents include, but are not limited to, monoclonal antibodies, cytokines, and small molecule inhibitors of signal transduction. UM2004/00031/00 CONFIDENTIAL HCT100414 20 * Subject is at least 21 days from prior chemotherapy and at least 30 days from prior non-cytotoxic therapy and is recovered from associated toxicities. * Subject must not have received radiotherapy for at least seven days. * Subject must be at least three weeks since last major surgery (a lesser period is acceptable if deemed in the best interest of the subject). Subject must have an ECOG Performance Status of 0 or 1 (refer to * Appendix 4, ECOG Performance Status). * Subject must have, at screening, a probable life expectancy of at least three months. * Subject of childbearing potential must be practicing adequate contraception \[e.g., oral contraceptives, diaphragm plus spermicide, or intrauterine device (IUD)\] or show documented complete abstinence from intercourse for at least three months prior to study start. The same contraceptive method should be used throughout the study and continue for at least four weeks after the end of the study. A subject will be considered of childbearing potential if not surgically sterile or post-menopausal (i.e., documented absence of menses for one year prior to entry into the study). 14\. Subject must have screening laboratory criteria as follows: * Hemoglobin ≥ 9.0 g/dL. * Neutrophils ≥ 1,500/mm³ \[≥1.5 x 10\^9/L\]. * Platelets ≥ 100,000/mm³ \[≥100.0 x 10\^9/L\]. * Creatinine ≤ upper limit of normal (ULN) or creatinine clearance (Clcreat) ≥ 60mL/min. * Creatinine clearance should be calculated using the Cockcroft-Gault formula: Clcreat (mL/min) = (140-age \[yr\] x body wt \[kg\] x 0.85 72 x serum creatinine \[mg/dL\] OR Clcreat (mL/min) = 1.05 x (140-age \[yr\] x body wt \[kg\] serum creatinine \[μmol/L\] * Serum bilirubin within normal limits. * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase \< 2xULN if liver metastases are absent by abdominal CT or MRI or \< 5xULN if liver metastases are present.
Exclusion criteria
A subject will not be eligible for inclusion in this study if any of the following criteria are met: * Subject is pregnant or lactating. * Subject has received more than one prior chemotherapy regimen. UM2004/00031/00 CONFIDENTIAL HCT100414 21 * Subject has concomitant or history of previous malignancies, with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for five years. * Subject has active uncontrolled infection. * Subject has brain metastases as documented by CT or MRI. Note: Asymptomatic subjects do not require CT or MRI to rule out brain metastases. * Subject has received prior treatment with HYCAMTIN. * Subject has a history of an allergic reaction to compounds chemically-related to HYCAMTIN or its constituents. * Subject has received any investigational agent within 30 days or five half-lives (whichever is longer) prior to study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | Week 0 to Week 98 when endpoints were met | Tumor response based on GOG (Gynecological Oncology Group) modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria. A 4-point scale used specifying tumor response. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions; (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; (PD): At least a 20% increase in the sum of the LD of target lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | Week 0 to Week 19 when endpoints were met | Kaplan-Meier Estimate. Time to progression is defined as time from start of treatment until the first documented sign of disease progression or death due to progressive disease. Subjects who have not progressed or died at the time of analysis will be censored at the time of initiation of alternative anti-cancer therapy or time of last contact. Percentiles represent a set of points on a scale arrived at by dividing a group into parts in order of magnitude. |
| Overall Survival | Week 0 to Week 98 | Kaplan-Meier Estimate. Overall survival is defined as time from start of treatment until death due to any cause. Subjects who are alive at the time of analysis will be censored at the time of last contact. |
| Response Duration | Week 0 to week 98 | The time from initial documented response to the first documented sign of progression or death due to progressive disease. Not calculated due to no Complete response and only 1 partial response. |
| Time to Response | Week 0 to week 98 | The time from start of treatment until the first documented response. Not calculated due to no Complete response and only 1 partial response. |
| Safety and Tolerability as Summarized Through Adverse Event Reporting | Week 0 to week 98 | AE = Adverse Event reported at a frequency of greater than or equal to 16%. SAE = Serious Adverse Events where all were reported at 0% frequency. |
Countries
Canada, Hungary, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topotecan Hydrochloride Subjects received IV weekly Topotecan administered at either 2.5 mg/m2(if the subject had prior pelvic radiotherapy) or 3.0 mg/m2 on Days 1, 8 and 15(+ or - 2 days) every 28 days. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other (Disease Progression) | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Sponsor Terminated Study | 9 |
Baseline characteristics
| Characteristic | Topotecan Hydrochloride |
|---|---|
| Age Continuous | 62.8 years STANDARD_DEVIATION 9.12 |
| Race/Ethnicity, Customized African Heritage/African American | 3 participants |
| Race/Ethnicity, Customized Caucasian | 34 participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / — |
| serious Total, serious adverse events | 11 / — |
Outcome results
Primary
Best Overall Response
Tumor response based on GOG (Gynecological Oncology Group) modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria. A 4-point scale used specifying tumor response. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions; (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; (PD): At least a 20% increase in the sum of the LD of target lesions
Time frame: Week 0 to Week 98 when endpoints were met
Population: Intent To Treat (ITT) Population - All subjects who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topotecan Hydrochloride | Best Overall Response | Complete Response | 0 Participants |
| Topotecan Hydrochloride | Best Overall Response | Partial Response | 1 Participants |
| Topotecan Hydrochloride | Best Overall Response | Stable Disease | 9 Participants |
| Topotecan Hydrochloride | Best Overall Response | Progressive Disease | 23 Participants |
| Topotecan Hydrochloride | Best Overall Response | Unknown | 4 Participants |
Secondary
Overall Survival
Kaplan-Meier Estimate. Overall survival is defined as time from start of treatment until death due to any cause. Subjects who are alive at the time of analysis will be censored at the time of last contact.
Time frame: Week 0 to Week 98
Population: Intent To Treat (ITT) Population - All subjects who received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Topotecan Hydrochloride | Overall Survival | 25th percentile | 20.4 Weeks |
| Topotecan Hydrochloride | Overall Survival | Median percentile | 47.3 Weeks |
| Topotecan Hydrochloride | Overall Survival | 75th percentile | 89.3 Weeks |
Secondary
Response Duration
The time from initial documented response to the first documented sign of progression or death due to progressive disease. Not calculated due to no Complete response and only 1 partial response.
Time frame: Week 0 to week 98
Secondary
Safety and Tolerability as Summarized Through Adverse Event Reporting
AE = Adverse Event reported at a frequency of greater than or equal to 16%. SAE = Serious Adverse Events where all were reported at 0% frequency.
Time frame: Week 0 to week 98
Population: Intent To Treat (ITT) Population - All subjects who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Fatigue | 15 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Nausea | 14 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Constipation | 12 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Abdominal Pain | 11 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Vomiting | 8 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Hypokalemia | 7 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Anorexia | 6 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Dyspnea | 6 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Diarrhea | 6 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Dizziness | 6 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Headache | 6 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Cerebral infarction | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Incisional hernia, obstructive | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Dehydration | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Embolism venous | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | Alive at last contact-when follow-up ended | 9 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | Deaths - any subject | 28 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | Cause of Death - Disease of Study | 25 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | Cause of Death - Non-Hematological toxicity | 2 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | Cause of Death - Other-Brain Metastases | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | AE: Insomnia | 6 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Abdominal Pain | 2 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Gastrointestinal hemorrhage | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Intestinal obstruction | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Rectal Hemorrhage | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Vomiting | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Pulmonary Embolism | 3 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Dyspnea | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Bacteremia | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Streptococcal Bacteremia | 1 Number of Events |
| Topotecan Hydrochloride | Safety and Tolerability as Summarized Through Adverse Event Reporting | SAE: Cerebral ischemia | 1 Number of Events |
Secondary
Time to Progression
Kaplan-Meier Estimate. Time to progression is defined as time from start of treatment until the first documented sign of disease progression or death due to progressive disease. Subjects who have not progressed or died at the time of analysis will be censored at the time of initiation of alternative anti-cancer therapy or time of last contact. Percentiles represent a set of points on a scale arrived at by dividing a group into parts in order of magnitude.
Time frame: Week 0 to Week 19 when endpoints were met
Population: Intent To Treat (ITT) Population - All subjects who received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Topotecan Hydrochloride | Time to Progression | 25th percentile | 7.3 Weeks |
| Topotecan Hydrochloride | Time to Progression | Median percentile | 8.7 Weeks |
| Topotecan Hydrochloride | Time to Progression | 75th percentile | 15.3 Weeks |
Secondary
Time to Response
The time from start of treatment until the first documented response. Not calculated due to no Complete response and only 1 partial response.
Time frame: Week 0 to week 98