Clinical trial NCT00025506: Thalidomide in Treating Patients With Recurrent or Persistent Carcinosarcoma of the Uterus
Official title: A Phase II Evaluation of Thalidomide (NSC #66847) in the Treatment of Recurrent or Persistent Carcinosarcoma of the Uterus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Uterine Corpus Sarcoma
Uterine Carcinosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Gynecologic Oncology Group
First posted: 2003-01-27
Enrollment: 55
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS) > 6 Months
timeFrame: Every other cycle for 6 months
measure: Frequency and Severity of Adverse Effects as Assessed by Common Toxicity Criteria (CTC) v2.0
timeFrame: Each cycle during treatment and 30 days after the last treatment (average 4 months)
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Every other cycle until progression or death, up to 5 years.
measure: Tumor Response
timeFrame: 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)
measure: Overall Survival
timeFrame: From study entry to death or last contact, up to 5 years.
measure: Initial Performance Status
timeFrame: baseline
measure: Initial Histologic Grade
timeFrame: Baseline
Other outcomes:
measure: Serum and Plasma Concentrations of VEGF and bFGF With PFS
timeFrame: Up to 5 years
measure: Serum and Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) and bFGF
timeFrame: Up to 5 years
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: D. McMeekin
role: PRINCIPAL_INVESTIGATOR
References: