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

NCT ID: NCT00231842

Last Updated: 2019-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-02-28
• Study Completion Date: 2011-07-31

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.

Conditions

Uterine Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ifosfamide with or without cisplatin

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.

Group Type: EXPERIMENTAL

Ifosfamide

Intervention Type: DRUG

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

Intervention Type: DEVICE

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.

Cisplatin

Intervention Type: DRUG

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

Interventions

Ifosfamide

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 Type: DRUG

Radiation 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.

Intervention Type: DEVICE

Cisplatin

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

Intervention Type: DRUG

Other Intervention Names

Pelvic RT, Radiation

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Montefiore Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Mark H. Einstein

Director, Clinical Research for Women's Health

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

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

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center and Albert Einstein College of Medicine

Locations

Montefiore Medical Center

The Bronx, New York, United States

Countries

United States

References

Einstein MH, Klobocista M, Hou JY, Lee S, Mutyala S, Mehta K, Reimers LL, Kuo DY, Huang GS, Goldberg GL. Phase II trial of adjuvant pelvic radiation "sandwiched" between ifosfamide or ifosfamide plus cisplatin in women with uterine carcinosarcoma. Gynecol Oncol. 2012 Jan;124(1):26-30. doi: 10.1016/j.ygyno.2011.10.008. Epub 2011 Nov 3.

Reference Type: RESULT

PMID: 22055846 (View on PubMed)

Other Identifiers

03-02-040

Identifier Type: -

Identifier Source: org_study_id