Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Uterine Neoplasms

Mixed Tumor, Mesodermal

Adenoma, Pleomorphic

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Neoplasms by Histologic Type

Sarcoma

Neoplasms, Connective and Soft Tissue

Malignant Mixed Mullerian Tumor

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

Ifosfamide

Isophosphamide mustard

Mesna

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

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.

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.

Radiation Therapy

dosage is 20 mg/m2/day for 5 days, ever 3 weeks.

Mark H Einstein, M.D., M.S.

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.

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 Radiation Therapy With Ifosfamide in Patients With Mixed Mesodermal Tumors of the Uterus

A Pilot Phase II Trial of Adjuvant Radiation Therapy "Sandwiched" Between Ifosfamide in Patients With Mixed Mesodermal Tumors

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.

Montefiore Medical Center

Director, Clinical Research for Women's Health

Adverse events were monitored for each cycle during therapy and during follow-up and graded using the National Cancer Institute Common Toxicity Criteria (CTC) version 3.0. Frequencies for toxicity and adverse events were recorded.

Although adverse events were monitored, however, not all adverse events are being reported. The PI and the study team have left the institution. Sincere efforts were made to obtain the data, however, the adverse events data is not available.

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.

Chemotherapy and Radiation Therapy

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Total Stage I

Total Stage II

Total Stage III

Total Stage IV

Federation of Gynecology and Obstetrics (FIGO) is a system for staging gynecologic cancer.

I Malignancy of one (Ia) or both (Ib) ovaries, without ascites; 5-year survival: 60%

II Malignancy of one (IIa) or both (IIb) ovaries, with pelvic extension and ascites; 5-year survival: 40%

III Malignancy involves one/both ovaries, intraperitoneal metastases outside pelvis and/or positive retroperitoneal lymph nodes; 5-year survival: 5%

IV Involvement of one/both ovaries with metastases and histologically confirmed extension to pleural cavity or liver; 5-year survival, 3%

FIGO Staging

Mark Einstein, MD, MS

Neutropenia

Anemia

Thrombocytopenia

Adjuvant Radiation Therapy "Sandwiched" between Ifosfamide in Patients with Mixed Mesodermal Tumors

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.

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.

Grade 3 Toxicity

Adjuvant Radiation Therapy "Sandwiched" between Ifosfamide in Patients with Mixed Mesodermal Tumors

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.

Grade 4 Toxicity

Cycles With Hematologic Toxicities

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Adjuvant Radiation Therapy With Ifosfamide in Patients With Mixed Mesodermal Tumors of the Uterus	NCT00231842	Uterine Cancer	Ifosfamide Radiation Thera... Cisplatin	18 Years -	Montefiore Medical Center
Adjuvant Radiation Therapy With Ifosfamide in Patients With Mixed Mesodermal Tumors of the Uterus	NCT00231842	Uterine Cancer	Ifosfamide Radiation Thera... Cisplatin	18 Years -	Montefiore Medical Center

Spots Global Cancer Trial Database for mixed mesodermal tumor