Clinical trial NCT00231842: Adjuvant Radiation Therapy With Ifosfamide in Patients With Mixed Mesodermal Tumors of the Uterus
Official title: A Pilot Phase II Trial of Adjuvant Radiation Therapy "Sandwiched" Between Ifosfamide in Patients With Mixed Mesodermal Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Uterine Cancer
Keywords: Mixed Mesodermal Tumor
MMT
Uterine Cancer
Radiation Therapy
Chemotherapy
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2005-10-04
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Cycles With Hematologic Toxicities
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Montefiore Medical Center and Albert Einstein College of Medicine
name: Mark H Einstein, M.D., M.S.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.