Adjuvant Chemotherapy for High Risk Uterine Leiomyosarcoma

Adjuvant Treatment of High Risk Uterine Leiomyosarcoma With Gemcitabine/Docetaxel Followed by Doxorubicin: A Phase II Trial

The purpose of this trial is to study the benefits of giving chemotherapy to women after they have had surgical resection of their primary disease and have no evidence of disease remaining(known as adjuvant therapy). The major objective of this study is to determine the progression free survival. The goal is to prevent relapse or recurrence of their uterine leiomyosarcoma.

Study Overview

• Status: Completed
• Conditions: Leiomyosarcoma; Uterine Neoplasm
• Intervention / Treatment: Drug: gemcitabine, docetaxel, doxorubicin

Detailed Description

Patients with a diagnosis of early-stage uterine leiomyosarcoma have a 70% chance of relapse or recurrence of their disease. Patients enrolled in this trial will receive 4 cycles of gemcitabine and docetaxel followed by 4 cycles of adriamycin. Following completion of chemotherapy, they will be have repeat imaging at regular intervals to monitor for disease recurrence along with periodic clinical evaluations.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Cancer Institute/Washington Hospital Center (Medstar)
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Winship Cancer Institute at Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Gynecologic Oncology
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General
    • Boston, Massachusetts, United States, 01225
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Oncology Hematology Associates
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• ≥ 18 years of age
• high risk uterine LMS, FIGO stage I or II
• pathology review of LMS high grade and /or mitotic rate greater than or equal to 5 mitoses/10 hpf
• no longer than 12 weeks from surgical resection of cancer
• no evidence of residual disease
• ECOG 0 or 1
• ANC ≥ 1,500, hemoglobin ≥ 8.0, platelets ≥100,000
• creatinine ≤ 1.5 x institutional upper limits of normal
• adequate liver function
• neuropathy (sensory and motor) ≤ CTC grade 1
• negative pregnancy test
• signed consent

Exclusion Criteria:

• patients with other invasive malignancies
• prior therapy with gemcitabine or docetaxel or doxorubicin
• hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
• women who are breast feeding
• cardiac ejection fraction <50%
• prior pelvic irradiation
• treatment with hormone replacement or anti-hormonal agents or other cytotoxic agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: gemcitabine/docetaxel then doxorubicin; Gemcitabine 900 mg/m2 IV over 90 minutes days 1 and 8 Docetaxel 75 mg/m2 IV day 8 (pre-medication dexamethasone 4-8 mg p.o. bid for 3 days, starting 12-24 hours prior to docetaxel). Doxorubicin 60 mg/m2 IVP every 21 days for 4 cycles (recommend use of central venous catheter access).	Drug: gemcitabine, docetaxel, doxorubicin; Cycles = 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Two-year Progression-free Survival Among Women Treated With This Adjuvant Regimen for High Risk Uterine LMS	Every 3 months up to two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability/Toxicity of This Regimen	Unacceptable toxicity is defined as grade 3 or 4 non-hematologic toxicity events that are considered to be treatment-related, excluding alopecia and fatigue.	Every 28 days during dosing and then every 3 months thereafter until patient comes off study
Correlation Between Age and Tumor Response to Treatment (PFS)		2 years
Correlation Between Menopausal Status at Diagnosis and Tumor Response to Treatment (PFS)		2 years
Correlation Between Uterine Serosal Involvement and Tumor Response to Treatment (PFS)	AJCC Stage I: No serosal involvement AJCC Stage II: No serosal involement AJCC Stage III: Serosal only	2 years
Correlation Between Mitotic Rate and Tumor Response to Treatment (PFS)	Mitotic rate is measured in mitoses per 10 high-power fields	2 years
Correlation Between Estrogen Receptor (ER) Status and Tumor Response to Treatment (PFS)		2 years
Correlation Between Progesterone Receptor (PR) Status and Tumor Response to Treatment (PFS)		2 years
Correlation Between 1988 FIGO Stage and Tumor Response to Treatment (PFS)	Stage I: confined to the uterine corpus Stage II: confined to corpus and cervix Stage IIIA: serosa involvement only (disease could involve the uterine serosa, but patients must have had no other evidence of local spread)	2 years
Correlation Between Estrogen Receptor (ER) or Progesterone Receptor (PR) Positive and Tumor Response to Treatment (PFS)		2 years

Collaborators and Investigators

• Sponsor: Sarcoma Alliance for Research through Collaboration
• Investigators: Principal Investigator: Martee L. Hensley, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Hensley ML, Wathen JK, Maki RG, Araujo DM, Sutton G, Priebat DA, George S, Soslow RA, Baker LH. Adjuvant therapy for high-grade, uterus-limited leiomyosarcoma: results of a phase 2 trial (SARC 005). Cancer. 2013 Apr 15;119(8):1555-61. doi: 10.1002/cncr.27942. Epub 2013 Jan 18.

Helpful Links

• SARC Website

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: January 24, 2006
• First Submitted That Met QC Criteria: January 24, 2006
• First Posted (Estimate): January 25, 2006

Study Record Updates

• Last Update Posted (Estimate): December 1, 2014
• Last Update Submitted That Met QC Criteria: November 23, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: uterine leiomyosarcoma; early stage; adjuvant treatment; high grade
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Uterine Diseases; Sarcoma; Neoplasms, Muscle Tissue; Leiomyosarcoma; Uterine Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Gemcitabine; Docetaxel; Doxorubicin
• Other Study ID Numbers: SARC005; MSKCC05-128 (Other Identifier: Memorial Sloan-Kettering Cancer Center)