Clinical trial NCT00379145: Trabectedin in Treating Patients With Advanced, Persistent, or Recurrent Leiomyosarcoma of the Uterus
Official title: A Phase II Evaluation of Trabectedin (Yondelis, R279741) in the Treatment of Advanced, Persistent, or Recurrent Uterine Leiomyosarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Keywords: uterine leiomyosarcoma
recurrent uterine sarcoma
stage III uterine sarcoma
stage IV uterine sarcoma
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-09-21
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0
timeFrame: CT scan or MRI if used to follow lesion for measurable disease every other cycle until disease progression for up to 5 years.
measure: Incidence of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
timeFrame: Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up
Secondary outcomes:
Other outcomes:
Locations:
city: El Pueblo De Nuestra Señora De Los Ángeles De Porciúncula
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Hartford
country: United States
facility: Helen and Harry Gray Cancer Center at Hartford Hospital
state: Connecticut
city: New Britain
country: United States
facility: George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus
state: Connecticut
city: Washington
country: United States
facility: Washington Cancer Institute at Washington Hospital Center
state: District of Columbia
city: Augusta
country: United States
facility: MBCCOP - Medical College of Georgia Cancer Center
state: Georgia
city: Macon
country: United States
facility: Central Georgia Gynecologic Oncology
state: Georgia
city: Savannah
country: United States
facility: Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Hinsdale
country: United States
facility: Hinsdale Hematology Oncology Associates
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Indianapolis Hospital
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Las Vegas
country: United States
facility: Women's Cancer Center - Lake Mead
state: Nevada
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital Cancer Care
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Mentor
country: United States
facility: Lake/University Ireland Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Abington
country: United States
facility: Rosenfeld Cancer Center at Abington Memorial Hospital
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: Chao Family Comprehensive Cancer Center
name: Bradley J. Monk, MD
role: STUDY_CHAIR
References:
citation: Tewari D, Saffari B, Cowan C, Wallick AC, Koontz MZ, Monk BJ. Activity of trabectedin (ET-743, Yondelis) in metastatic uterine leiomyosarcoma. Gynecol Oncol. 2006 Sep;102(3):421-4. doi: 10.1016/j.ygyno.2006.04.025. Epub 2006 Jun 23.
citation: Monk BJ, Blessing JA, Street DG, Muller CY, Burke JJ, Hensley ML. A phase II evaluation of trabectedin in the treatment of advanced, persistent, or recurrent uterine leiomyosarcoma: a gynecologic oncology group study. Gynecol Oncol. 2012 Jan;124(1):48-52. doi: 10.1016/j.ygyno.2011.09.019. Epub 2011 Oct 13.