Clinical trial NCT00231842
Conditions: Uterine Cancer
Keywords: Mixed Mesodermal Tumor MMT Uterine Cancer Radiation Therapy Chemotherapy
Sponsor: Montefiore Medical Center
Start date: 2003-02-01; Completion date: 2011-07-01
Enrollment: 30 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: Participants with surgically staged carcinosarcoma (CS) with no gross residual disease were initially administered ifosfamide (1.2 g/m2/day for 5 days) with cisplatin (20 mg/m2/day for 5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin with cisplatin (20 mg/m2/day for 5 days) evrey 3 weeks. cisplatin added toxicity without additional efficacy, so mid-study, cisplatin was eliminated.
Interventions: intervention 1: Ifosfamide intervention 2: Radiation Therapy intervention 3: Cisplatin
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: dosage is 20 mg/m2/day for 5 days, ever 3 weeks.

Protocol documents: