Brief Summary
The optimal sequence and /or modality for adjuvant therapy in the management of Mixed Mesodermal Tumors (MMT) clearly remains to be established. The rationale for the protocol is to "sandwich" pelvic radiation with chemotherapy to decrease distant metastasis.
The proposed study will sandwich radiation between the two most active chemotherapeutic agents for MMT identified to date (ifosfamide/cisplatin). By doing so, we attempt to decrease both local and distant recurrence, which may translate into an improved progression free interval and possibly even extend survival.
The proposed study will sandwich radiation between the two most active chemotherapeutic agents for MMT identified to date (ifosfamide/cisplatin). By doing so, we attempt to decrease both local and distant recurrence, which may translate into an improved progression free interval and possibly even extend survival.
Brief Title
Adjuvant Radiation Therapy With Ifosfamide in Patients With Mixed Mesodermal Tumors of the Uterus
Detailed Description
Uterine sarcomas account for only 2-4% of uterine malignancies, yet they are responsible for 26% of uterine cancer deaths. Mixed mesodermal tumors (MMT), previously known as carcinosarcoma, are the most common of the uterine sarcomas in the United States. Prognosis for these patients is generally grim due to the propensity for early metastatic disease. Patterns of spread are by both hematogenous and lymphatic dissemination. It has been noted that 66% of patients with disease clinically confined to the uterus have nodal metastasis at the time of diagnosis. The majority of patients will die with both wide spread intra-abdominal and pelvic disease within two years of diagnosis.
Adjuvant pelvic radiation therapy has been advantageous in controlling local recurrence. One study reports 26% local recurrence in patients treated with surgery alone versus 14% recurrence in patients treated with surgery and adjuvant pelvic radiation. Although adjuvant radiation shows a benefit in improving local control, it has not been found to impact survival. This finding is likely attributed to the high incidence of distant metastasis (85%) known to occur with disease recurrence.
Multiple chemotherapeutic agents have been evaluated in the management of advanced, persistent or recurrent uterine MMT. Response to single agent therapy has been less than 35% with the most active agents identified being ifosfamide (response rate = 34.8%) and cisplatin (response rate 17.9%. The use of chemotherapy in the adjuvant setting has been explored as a means of attempting to impact the incidence of distant metastasis.
Adjuvant pelvic radiation therapy has been advantageous in controlling local recurrence. One study reports 26% local recurrence in patients treated with surgery alone versus 14% recurrence in patients treated with surgery and adjuvant pelvic radiation. Although adjuvant radiation shows a benefit in improving local control, it has not been found to impact survival. This finding is likely attributed to the high incidence of distant metastasis (85%) known to occur with disease recurrence.
Multiple chemotherapeutic agents have been evaluated in the management of advanced, persistent or recurrent uterine MMT. Response to single agent therapy has been less than 35% with the most active agents identified being ifosfamide (response rate = 34.8%) and cisplatin (response rate 17.9%. The use of chemotherapy in the adjuvant setting has been explored as a means of attempting to impact the incidence of distant metastasis.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Uterine Cancer
Eligibility Criteria
Inclusion Criteria:
* Histologically documented mixed mesodermal tumor (MMT) of uterus with no visible residual disease.
* Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node sampling.
* Surgical staging should be completed 6 weeks ± 7 days prior to enrollment.
* Age \>= 18 years.
* Written voluntary informed consent.
Exclusion Criteria:
* Patient has impairment of hepatic, renal or hematologic function as defined by the following baseline laboratory values:
* Total serum bilirubin \>1.5mg/dl
* History of chronic or active hepatitis
* Serum creatinine \>2.0 mg/dl
* Platelets \<100,000/mm3
* Absolute neutrophil count (ANC) \<1500/mm3
* Hemoglobin \<8.0 g/dl (the patient may be transfused prior to study entry)
* Patient has severe or uncontrolled medical disease (eg. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)
* Patient has been treated with myelosuppressive chemotherapy within three weeks prior to study entry.
* Patients with any prior chemotherapy or radiotherapy for pelvic malignancy.
* Patients with dementia or altered mental status that would prohibit the giving and understanding of informed consent at time of study entry.
* Patient has a uterine sarcoma other then mixed mesodermal tumor (MMT).
* Histologically documented mixed mesodermal tumor (MMT) of uterus with no visible residual disease.
* Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node sampling.
* Surgical staging should be completed 6 weeks ± 7 days prior to enrollment.
* Age \>= 18 years.
* Written voluntary informed consent.
Exclusion Criteria:
* Patient has impairment of hepatic, renal or hematologic function as defined by the following baseline laboratory values:
* Total serum bilirubin \>1.5mg/dl
* History of chronic or active hepatitis
* Serum creatinine \>2.0 mg/dl
* Platelets \<100,000/mm3
* Absolute neutrophil count (ANC) \<1500/mm3
* Hemoglobin \<8.0 g/dl (the patient may be transfused prior to study entry)
* Patient has severe or uncontrolled medical disease (eg. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)
* Patient has been treated with myelosuppressive chemotherapy within three weeks prior to study entry.
* Patients with any prior chemotherapy or radiotherapy for pelvic malignancy.
* Patients with dementia or altered mental status that would prohibit the giving and understanding of informed consent at time of study entry.
* Patient has a uterine sarcoma other then mixed mesodermal tumor (MMT).
Inclusion Criteria
Inclusion Criteria:
* Histologically documented mixed mesodermal tumor (MMT) of uterus with no visible residual disease.
* Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node sampling.
* Surgical staging should be completed 6 weeks ± 7 days prior to enrollment.
* Age \>= 18 years.
* Written voluntary informed consent.
* Histologically documented mixed mesodermal tumor (MMT) of uterus with no visible residual disease.
* Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node sampling.
* Surgical staging should be completed 6 weeks ± 7 days prior to enrollment.
* Age \>= 18 years.
* Written voluntary informed consent.
Gender
Female
Gender Based
false
Keywords
Mixed Mesodermal Tumor
MMT
Uterine Cancer
Radiation Therapy
Chemotherapy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT00231842
Org Class
Other
Org Full Name
Montefiore Medical Center
Org Study Id
03-02-040
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Pilot Phase II Trial of Adjuvant Radiation Therapy "Sandwiched" Between Ifosfamide in Patients With Mixed Mesodermal Tumors
Primary Outcomes
Outcome Description
Out of 162 planned cycles, a total of 138 cycles (85%) were administered. Number of cycles during which participants with grades 3 and 4 experienced hematologic toxicities are reported. Most of the toxicities were self-limiting.
Outcome Measure
Cycles With Hematologic Toxicities
Outcome Time Frame
2 years
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Mark Einstein
Investigator Email
meinstei@montefiore.org
Investigator Phone