Uterine Cancer
Conditions
Keywords
Mixed Mesodermal Tumor, MMT, Uterine Cancer, Radiation Therapy, Chemotherapy
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.
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.
Interventions
DEVICERadiation Therapy
Ifosfamide 1.2gm/m2/day for 5 days. Mesna 400mg/IV bolus at each ifosfamide dosing followed by 1200mg IV divided in 3L / day x 5 days. Repeat q21 days x 3 cycles. After 3 cycles, RT. After RT, Ifosfamide 1.0gm/m2/day for 5 days. Mesna 333 mg /IV bolus at each ifosfamide dosing followed by 1000mg IV divided in 3L /day x 5 days. Repeat q21 days x 3 cycles.
DRUGIfosfamide
Ifosfamide 1.2gm/m2/day for 5 days. Mesna 400mg/IV bolus at each ifosfamide dosing followed by 1200mg IV divided in 3L / day x 5 days. Repeat q21 days x 3 cycles. After 3 cycles, RT. After RT, Ifosfamide 1.0gm/m2/day for 5 days. Mesna 333 mg/IV bolus at each ifosfamide dosing followed by 1000mg IV divided in 3L /day x 5 days. Repeat q21 days x 3 cycles.
DRUGCisplatin
dosage is 20 mg/m2/day for 5 days, ever 3 weeks.
Sponsors
Montefiore Medical Center
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
* 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cycles With Hematologic Toxicities | 2 years | 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. |
Countries
United States
Participant flow
Recruitment details
Eligible participants with surgically staged I-IV uterine carcinosarcoma (CS) without evidence of gross residual disease after primary surgery were recruited from 1999 to 2009 . Eligible participants underwent surgical staging when clinically indicated.
Pre-assignment details
30 participants were enrolled and 3 participants withdrew prior to therapy. Twenty-seven participants received the first three cycles of chemotherapy and Radiation Therapy and were included in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy and Radiation Therapy Adjuvant Radiation Therapy Sandwiched between Ifosfamide in Patients with Mixed Mesodermal Tumors
Radiation Therapy : Ifosfamide 1.2gm/m2/day for 5 days. Mesna 400mg/IVSS bolus at each ifosfamide dosing followed by 1200mg IV divided in 3L/day x 5 days. Repeat q21 days x 3 cycles. After 3 cycles, RT. After RT, Ifosfamide 1.0gm/m2/day for 5 days. Mesna 333mg/IVSS bolus at each ifosfamide dosing followed by 1000mg IV divided in 3L/day x 5 days. Repeat q21 days x 3 cycles.
Ifosfamide : Ifosfamide 1.2gm/m2/day for 5 days. Mesna 400mg/IVSS bolus at each ifosfamide dosing followed by 1200mg IV divided in 3L/day x 5 days. Repeat q21 days x 3 cycles. After 3 cycles, RT. After RT, Ifosfamide 1.0gm/m2/day for 5 days. Mesna 333mg/IVSS bolus at each ifosfamide dosing followed by 1000mg IV divided in 3L/day x 5 days. Repeat q21 days x 3 cycles. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not complete the last 3 cycle | 8 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Chemotherapy and Radiation Therapy |
|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| FIGO Staging Total Stage I | 14 Participants |
| FIGO Staging Total Stage II | 3 Participants |
| FIGO Staging Total Stage III | 7 Participants |
| FIGO Staging Total Stage IV | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 27 |
| other Total, other adverse events | 0 / 27 |
| serious Total, serious adverse events | 13 / 27 |
Outcome results
Primary
Cycles With Hematologic Toxicities
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.
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Grade 3 Toxicity | Cycles With Hematologic Toxicities | Neutropenia | 11 Cycles |
| Grade 3 Toxicity | Cycles With Hematologic Toxicities | Anemia | 6 Cycles |
| Grade 3 Toxicity | Cycles With Hematologic Toxicities | Thrombocytopenia | 6 Cycles |
| Grade 4 Toxicity | Cycles With Hematologic Toxicities | Neutropenia | 14 Cycles |
| Grade 4 Toxicity | Cycles With Hematologic Toxicities | Anemia | 0 Cycles |
| Grade 4 Toxicity | Cycles With Hematologic Toxicities | Thrombocytopenia | 2 Cycles |