Thalidomide in Treating Patients With Recurrent or Persistent Carcinosarcoma of the Uterus

Phase 2

Completed

Conditions: Uterine Carcinosarcoma
Recurrent Uterine Corpus Sarcoma

Interventions: Other: Laboratory Biomarker Analysis
Drug: Thalidomide

Registration Number: NCT00025506

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial is studying how well thalidomide works in treating patients with carcinosarcoma of the uterus that has come back or that does not go to remission (decrease or disappear but may still be in the body) despite treatment. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor.

Detailed Description: OBJECTIVES: Primary I. Determine the antitumor cytostatic activity of thalidomide, as measured by the probability of progression-free survival (PFS) for at least 6 months, in patients with recurrent or persistent uterine carcinosarcoma.

II. Determine the nature and degree of toxicity of this drug in these patients.

Secondary I. Determine the partial and complete response rates in patients treated with this drug.

II. Determine the duration of PFS and overall survival of patients treated with this drug.

III. Determine the effect of this drug on initial performance status and histological grade in these patients.

IV. Correlate serum and plasma biomarkers, including vascular endothelial growth factor and basic fibroblast growth factor, with clinical outcome (i.e., PFS) in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral thalidomide once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 19-51 patients will be accrued for this study within 3 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 55

Inclusion Criteria

Histologically confirmed uterine sarcoma
- Carcinosarcoma (malignant mixed müllerian tumor)
  - Homologous or heterologous type
Recurrent or persistent with documented disease progression after prior local therapy
At least 1 unidimensionally measurable target lesion
- At least 20 mm by conventional techniques, including palpation, plain x-ray, CT scan, or MRI
- At least 10 mm by spiral CT scan
- Tumors within a previously irradiated field are considered non-target lesions
Must have received 1 prior initial chemotherapy regimen (including high-dose ,consolidation, or extended therapy after surgical or nonsurgical assessment) for carcinosarcoma
No documented brain metastases since diagnosis of cancer
- Patients with stable CNS deficits are allowed provided that there is no evidence of brain metastases on CT scan or MRI
Ineligible for a higher priority Gynecologic Oncology Group (GOG) protocol (if one exists), including any active phase III GOG protocol for the same patient population
Performance status - GOG 0-2 if received 1 prior therapy regimen
Performance status - GOG 0-1 if received 2 prior therapy regimens
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Bilirubin no greater than 1.5 times upper limit of normal (ULN)
SGOT no greater than 2.5 times ULN
Alkaline phosphatase no greater than 2.5 times ULN
Creatinine no greater than 1.5 times ULN
Creatinine clearance greater than 60 mL/min
Not pregnant
Negative pregnancy test
Fertile patients must use at least 1 highly active method of contraception and 1 additional effective method of contraception for at least 4 weeks before, during, and for at least 4 weeks after study participation
No seizure disorders since diagnosis of cancer
- Patients with a history of seizure disorders are allowed provided that the seizures have been stable (i.e., no seizure within the past 12 months) while on an appropriately monitored treatment regimen
No active infection requiring antibiotics
No greater than grade 1 sensory or motor neuropathy
No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
At least 3 weeks since prior immunologic agents for uterine sarcoma
No prior thalidomide
See Disease Characteristics
At least 3 weeks since prior chemotherapy for uterine sarcoma and recovered
No more than 1 prior cytotoxic chemotherapy regimen for recurrent or persistent uterine sarcoma
No prior non-cytotoxic chemotherapy for recurrent or persistent uterine sarcoma
No concurrent bisphosphonates (e.g., zoledronate)
At least 1 week since prior hormonal therapy for uterine sarcoma
Concurrent hormone replacement therapy allowed
See Disease Characteristics
At least 3 weeks since prior radiotherapy for uterine sarcoma and recovered
No prior radiotherapy to more than 25% of marrow-bearing areas
See Disease Characteristics
Recovered from prior surgery
At least 3 weeks since any other prior therapy for uterine sarcoma
No prior anticancer therapy that would preclude study

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (thalidomide)	Laboratory Biomarker Analysis	Patients receive oral thalidomide once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (thalidomide)	Thalidomide	Patients receive oral thalidomide once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Frequency and Severity of Adverse Effects as Assessed by Common Toxicity Criteria (CTC) v2.0	Each cycle during treatment and 30 days after the last treatment (average 4 months)
Progression-free Survival (PFS) > 6 Months	Every other cycle for 6 months	Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	Every other cycle until progression or death, up to 5 years.	Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Tumor Response	For those patients whose disease can be evaluated by physical examination, response was assessed prior to each 28-day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle. (average = 4 months)	RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
Overall Survival	From study entry to death or last contact, up to 5 years.	The observed length of life from entry into the study to death or the date of last contact.
Initial Performance Status	baseline	Performance status 0 = Fully active, able to carry on all pre-disease performance without restriction. Performance status 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, e.g., light housework, office work. Performance status 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours.
Initial Histologic Grade	Baseline	G3 - Predominantly solid or entirely undifferentiated carcinoma. Not graded - tumor grade not reported.