Trabectedin in Treating Patients With Advanced, Persistent, or Recurrent Leiomyosarcoma of the Uterus

A Phase II Evaluation of Trabectedin (Yondelis, R279741) in the Treatment of Advanced, Persistent, or Recurrent Uterine Leiomyosarcomas

RATIONALE: Drugs used in chemotherapy, such as trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well trabectedin works in treating patients with advanced, persistent, or recurrent leiomyosarcoma of the uterus.

OBJECTIVES:

• Determine the antitumor activity of trabectedin, as measured by frequency and duration of objective response, in patients with advanced, persistent, or recurrent uterine leiomyosarcoma.
• Determine the nature and degree of toxicity of this drug in these patients.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive trabectedin IV continuously over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve a confirmed complete response may receive at least 2 additional courses.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed uterine leiomyosarcoma

  • Histological confirmation of original primary tumor required

• Advanced, persistent, or recurrent disease

  • Documented disease progression

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques, including palpation, plain x-ray, CT scan, and MRI OR ≥ 10 mm by spiral CT scan

  • At least 1 target lesion

    • Tumors within a previously irradiated field are considered nontarget lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiotherapy

• Ineligible for a higher priority GOG protocol (i.e., any active phase III GOG protocol for the same patient population)

PATIENT CHARACTERISTICS:

• GOG performance status 0-2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Platelet count ≥ 100,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin > 9.0 g/dL
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin normal
• AST ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 1.5 times ULN
• CPK ≤ ULN
• No active infection requiring antibiotics (except for patients with uncomplicated UTI)
• No neuropathy (sensory or motor) > grade 1
• No other invasive malignancy within the past 5 years except for nonmelanoma skin cancer
• No known active liver disease or hepatitis
• Must be willing/able to have a central venous catheter

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from prior surgery, radiotherapy, or other therapy

• No prior cancer treatment that would preclude study therapy

• No prior cytotoxic chemotherapy or biologic therapy for uterine sarcoma

• No prior chemotherapy for any abdominal or pelvic tumor within the past 5 years

  • Prior adjuvant chemotherapy for localized breast cancer is allowed provided it was completed more than 3 years ago and there is no evidence of recurrent or metastatic disease

• No prior trabectedin

• No prior radiotherapy within the past 5 years to any portion of the abdominal cavity or pelvis other than for treatment of uterine sarcoma

  • Prior radiotherapy for localized cancer of the breast, head and neck or skin is allowed, provided that it was completed more than 3 years ago and there is no evidence of recurrent or metastatic disease

• At least 1 week since prior hormonal therapy for the malignancy (continuation of hormone replacement therapy is permitted)

• No concurrent amifostine or other protective agents