Tumors
Conditions
Keywords
Solid Tumors
Brief summary
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.
Interventions
DRUGOral Topotecan
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.
Sponsors
GlaxoSmithKline
Accelerated Community Oncology Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient provides written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice. * Male or female patients. * Patient is at least 18 years of age with recurrent or persistent solid tumors. * Patient has adequate hematologic function (absolute neutrophil count \[ANC\] \>= 1500/mL and platelets \>= 100,000/mL), adequate renal function (serum creatinine \< 2.0 mg/dL; calculated creatinine clearance \> 40 mL/min), and adequate hepatic function (serum bilirubin \<= 1.5 mg/dL and transaminases \<= 3 times the upper limit of normal \[3 x ULN\]). * Patient has Eastern Oncology Cooperative Group (ECOG) performance status of \<= 2. * Patient has a life expectancy of at least 3 months at time of enrollment. * Patient has no medical problems, unrelated to the malignancy, of sufficient severity which would limit full compliance with the study or which would expose him/her to undue risks. * Patient has received no more than 2 prior treatment regimens prior to enrollment including chemotherapy, hormonal therapy, biologic therapy, and immunotherapy. * Patient has a negative serum or urine pregnancy test within 7 days prior to starting therapy (if a female of childbearing potential).
Exclusion criteria
* Patient is a pregnant or lactating woman. Women of childbearing potential with either a positive or no pregnant test (serum or urine) at baseline. Women of childbearing potential not using a reliable and appropriate contraceptive method will be excluded. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.) Patients must agree to continue contraception for 30 days from the date of the last study drug administration. * Patient has serious, uncontrolled, concurrent infection(s). * Patient has received whole pelvic or extended field radiation therapy within 4 weeks of enrollment. Patients who have not fully recovered or whose acute toxicity related to prior radiotherapy has not returned to baseline are ineligible. * Patient has received myelosuppressive chemotherapy within the last 4 weeks or has not recovered from the myelosuppressive effects of recent chemotherapy. * Patient has received another investigational agent within 4 weeks prior to study enrollment. * Patient has known hypersensitivity to topoisomerase I inhibitors. * Patient is unable to swallow a capsule or has a disease known to affect drug absorption, such as short gut syndrome or active radiation enteritis. * Patient has received drugs known to alter absorption such as antacids, proton pump blockers (eg, omeprazole), or H2 receptor antagonists (eg, cimetidine). A washout period of one week (7 days) is required prior to initiating study medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Single Agent Metronomic Oral Topotecan | MTD was assessed during the first cycle of treatment (days 1-28). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLT) | DLTs were assessed during the first cycle of treatment (days 1-28). | 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. |
| Best Overall Response | 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. | 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. |
Countries
United States
Participant flow
Recruitment details
The study was open to enrollment at one community oncology clinic from November 2006 to May 2009.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Metronomic Oral Topotecan All subjects received metronomic oral topotecan daily at the assigned dose level. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Metronomic Oral Topotecan |
|---|---|
| Age Continuous | 65.6 years STANDARD_DEVIATION 8.99 |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 3 / 3 | 13 / 14 | 2 / 2 |
| serious Total, serious adverse events | 1 / 3 | 0 / 4 | 0 / 3 | 7 / 14 | 1 / 2 |
Outcome results
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.
Time frame: MTD was assessed during the first cycle of treatment (days 1-28).
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metronomic Oral Topotecan | Maximum Tolerated Dose (MTD) of Single Agent Metronomic Oral Topotecan | 1.0 mg/day |
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.
Time frame: 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.
Population: All enrolled subjects were analyzed for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metronomic Oral Topotecan | Best Overall Response | Progressive Disease | 0 participants |
| Metronomic Oral Topotecan | Best Overall Response | Complete Response | 0 participants |
| Metronomic Oral Topotecan | Best Overall Response | Not Evaluable | 1 participants |
| Metronomic Oral Topotecan | Best Overall Response | Partial Response | 0 participants |
| Metronomic Oral Topotecan | Best Overall Response | Stable Disease | 2 participants |
| Oral Topotecan 0.50 mg Daily | Best Overall Response | Progressive Disease | 1 participants |
| Oral Topotecan 0.50 mg Daily | Best Overall Response | Stable Disease | 1 participants |
| Oral Topotecan 0.50 mg Daily | Best Overall Response | Partial Response | 0 participants |
| Oral Topotecan 0.50 mg Daily | Best Overall Response | Not Evaluable | 2 participants |
| Oral Topotecan 0.50 mg Daily | Best Overall Response | Complete Response | 0 participants |
| Oral Topotecan 0.75 mg Daily | Best Overall Response | Stable Disease | 2 participants |
| Oral Topotecan 0.75 mg Daily | Best Overall Response | Complete Response | 0 participants |
| Oral Topotecan 0.75 mg Daily | Best Overall Response | Partial Response | 0 participants |
| Oral Topotecan 0.75 mg Daily | Best Overall Response | Progressive Disease | 1 participants |
| Oral Topotecan 0.75 mg Daily | Best Overall Response | Not Evaluable | 0 participants |
| Oral Topotecan 1.0 mg Daily | Best Overall Response | Not Evaluable | 7 participants |
| Oral Topotecan 1.0 mg Daily | Best Overall Response | Complete Response | 0 participants |
| Oral Topotecan 1.0 mg Daily | Best Overall Response | Progressive Disease | 2 participants |
| Oral Topotecan 1.0 mg Daily | Best Overall Response | Stable Disease | 4 participants |
| Oral Topotecan 1.0 mg Daily | Best Overall Response | Partial Response | 1 participants |
| Oral Topotecan 1.25 mg Daily | Best Overall Response | Stable Disease | 0 participants |
| Oral Topotecan 1.25 mg Daily | Best Overall Response | Progressive Disease | 0 participants |
| Oral Topotecan 1.25 mg Daily | Best Overall Response | Complete Response | 0 participants |
| Oral Topotecan 1.25 mg Daily | Best Overall Response | Not Evaluable | 2 participants |
| Oral Topotecan 1.25 mg Daily | Best Overall Response | Partial Response | 0 participants |
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.
Time frame: DLTs were assessed during the first cycle of treatment (days 1-28).
Population: Number of participants analyzed refers to those for whom DLT information was available during the dose finding portion of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metronomic Oral Topotecan | Dose Limiting Toxicities (DLT) | 0 participants |
| Oral Topotecan 0.50 mg Daily | Dose Limiting Toxicities (DLT) | 0 participants |
| Oral Topotecan 0.75 mg Daily | Dose Limiting Toxicities (DLT) | 0 participants |
| Oral Topotecan 1.0 mg Daily | Dose Limiting Toxicities (DLT) | 0 participants |
| Oral Topotecan 1.25 mg Daily | Dose Limiting Toxicities (DLT) | 2 participants |