Recurrent Uterine Sarcoma, Stage III Uterine Sarcoma, Stage IV Uterine Sarcoma, Uterine Carcinosarcoma
Conditions
Brief summary
Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. This phase II trial is studying how well sorafenib works in treating patients with advanced or recurrent uterine cancer.
Detailed description
PRIMARY OBJECTIVES: I. Determine the objective response rate in patients with advanced or recurrent uterine cancer treated with sorafenib. II. Determine the toxic effects of this drug in these patients. SECONDARY OBJECTIVES: I. Determine progression-free survival of patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to histology (carcinoma vs carcinosarcoma). Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGsorafenib tosylate
Given orally
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* No prior sorafenib * Histologically or cytologically confirmed uterine carcinoma or carcinosarcoma: * Advanced or recurrent disease * Not amenable to curative surgery or radiotherapy * Measurable disease: * At least 1 unidimensionally measurable lesion \>= 20 mm by conventional techniques OR \>= 10 mm by spiral CT scan * Tumor tissue block must be available * No known brain metastases * Performance status: * ECOG 0-2 OR * Karnofsky 60-100% * Hematopoietic: * Absolute neutrophil count \>= 1,500/mm3 * Platelet count \>= 100,000/mm3 * No bleeding diathesis * Hepatic: * Bilirubin normal * AST and ALT =\< 2.5 times upper limit of normal * Renal: * Creatinine =\< 1.5 mg/dL OR * Creatinine clearance \>= 60 mL/min * Cardiovascular: * No uncontrolled hypertension, defined by 1 of the following: * Blood pressure \> 150/100 mm Hg * Currently taking \> 1 antihypertensive agent * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other active malignancy * No history of allergic reactions attributed to compounds of similar chemical or biological composition to sorafenib * No ongoing or active infection * No psychiatric illness or social situation that would preclude study compliance * No swallowing dysfunction that would preclude study drug ingestion * No other uncontrolled illness * Prior biological response modifier therapy allowed * No prior antiangiogenesis therapy * No prior MAPK-signaling agents * No prior vascular endothelial growth factor receptor (VEGFR) inhibitors * No more than 1 prior chemotherapy regimen * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) * Prior hormonal therapy allowed * Prior radiotherapy allowed provided the only site of measurable disease was not located within the radiation port OR disease has progressed since completion of therapy * Recovered from all prior therapy * Concurrent warfarin allowed provided all of the following are true: * Patient is therapeutic on a stable warfarin dose * INR target range =\< 3 * Patient is monitored with weekly INR testing * No active bleeding or pathological condition that carries a high bleeding risk * No concurrent combination antiretroviral therapy for HIV-positive patients * No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital) * No concurrent rifampin * No concurrent Hypericum perforatum (St. John's wort) * No other concurrent investigational agents * No other concurrent anticancer therapy * More than 4 weeks since prior radiotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Overall Response Rate | Up to 5 years | Response was defined using the Response Evaluation Criteria in Solid Tumors (RECIST, http://www.ncbi.nlm.nih.gov/pubmed/10655437#): Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 5 years | Defined as the time from the first day of therapy to the date of death. If the patient was lost to follow-up, survival was censored on the last date the patient was known to be alive. |
| Progression Free Survival | Up to 5 years | Defined as the time from the first day of treatment until the date PD(progressive disease) or death is first reported. Patients who died without a reported prior progression was considered to have progressed on the day of their death. Patients who did not progress was censored at the day of their last tumor assessment. According to RECIST, progressive disease(PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions. |
| Duration of Response | Up to 5 years | Duration of response was measured from the time measurement criteria are met for CR(complete response)/PR(partial response), whichever was first recorded, until the first date that PD(progressive disease) was objectively documented. According to the RECIST: Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; progressive disease(PD), at least a 20% increase in the sum of the longest diameter of target lesions. |
Countries
Canada, United States
Participant flow
Recruitment details
The study population consisted of patients at least 18 years old with advanced or recurrent carcinoma, or uterine carcinosarcoma. Both cohorts received a starting dose of 400 mg sorafenib orally twice daily on a continuous basis.
Pre-assignment details
A Simon optimal two-stage design was used with objective response rate as the primary efficacy endpoint.
Participants by arm
| Arm | Count |
|---|---|
| Carcinoma Patients with advanced uterine carcinoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | 40 |
| Carcinosarcoma Patients with advanced uterine carcinosarcoma receive 400 mg oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | 16 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Carcinosarcoma | Total | Carcinoma |
|---|---|---|---|
| Age, Customized | 64 years | 64 years | 64 years |
| Histology Adenocarcinoma (unspecified) | 0 participants | 12 participants | 12 participants |
| Histology Carcinosarcoma | 16 participants | 16 participants | 0 participants |
| Histology Clear cell | 0 participants | 1 participants | 1 participants |
| Histology Endometrioid | 0 participants | 24 participants | 24 participants |
| Histology Serous | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized African-American | 3 participants | 5 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 7 participants | 5 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 5 participants | 4 participants |
| Race/Ethnicity, Customized Non-Hispanic white | 10 participants | 39 participants | 29 participants |
| Sex: Female, Male Female | 16 Participants | 56 Participants | 40 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 56 / 56 |
| serious Total, serious adverse events | 11 / 56 |
Outcome results
Primary
Objective Overall Response Rate
Response was defined using the Response Evaluation Criteria in Solid Tumors (RECIST, http://www.ncbi.nlm.nih.gov/pubmed/10655437#): Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR.
Time frame: Up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Carcinoma | Objective Overall Response Rate | 2 participants |
| Carcinosarcoma | Objective Overall Response Rate | 0 participants |
Secondary
Duration of Response
Duration of response was measured from the time measurement criteria are met for CR(complete response)/PR(partial response), whichever was first recorded, until the first date that PD(progressive disease) was objectively documented. According to the RECIST: Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; progressive disease(PD), at least a 20% increase in the sum of the longest diameter of target lesions.
Time frame: Up to 5 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Carcinoma | Duration of Response | 25 Month |
Secondary
Overall Survival
Defined as the time from the first day of therapy to the date of death. If the patient was lost to follow-up, survival was censored on the last date the patient was known to be alive.
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carcinoma | Overall Survival | 11.4 Month |
| Carcinosarcoma | Overall Survival | 5 Month |
Secondary
Progression Free Survival
Defined as the time from the first day of treatment until the date PD(progressive disease) or death is first reported. Patients who died without a reported prior progression was considered to have progressed on the day of their death. Patients who did not progress was censored at the day of their last tumor assessment. According to RECIST, progressive disease(PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions.
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carcinoma | Progression Free Survival | 3.2 Month |
| Carcinosarcoma | Progression Free Survival | 1.8 Month |