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Activity of Trabectedin or Gemcitabine + Docetaxel in Uterine Leiomyosarcoma (TAUL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02249702
Recruitment Status : Completed
First Posted : September 25, 2014
Last Update Posted : December 6, 2017
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research

Brief Summary:

The management of patients with uterine leiomyosarcomas poses many difficulties. Despite 60% of women present with disease limited to the uterus, cure rates range from 20 to 60%. Patients with metastatic disease at diagnosis or who recur after initial treatment have a dismal prognosis and, except for a subset of selected patients with completely resectable disease, the median survival is less than one year. Treatment options for recurrent/metastatic uterine leiomyosarcoma are limited. The most active drugs are doxorubicin ± ifosfamide and gemcitabine + docetaxel (GD) with response rate of 25-55% and 27-53%, respectively. Both these regimens have been increasingly used in the last years also in the adjuvant setting. For relapsed patients other drugs have been tested as single agent but negligible activity was observed.

Trabectedin (Yondelis® -T) is a marine-derived cytotoxic approved by EMEA. It is indicated for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide or who are unsuitable to receive these agents. Among STS, activity has been mainly detected in synovial sarcoma, liposarcoma and leiomyosarcoma. Although the response rate did not exceed 10%, T was demonstrated to provide disease control, with progression arrest rates exceeding 50% and progression-free survival rates exceeding 20% at 6 months. So far no phase II studies tested the activity of T in uterine leiomyosarcoma specifically. This study is aimed at evaluating the activity of T (arm A) in advanced uterine leiomyosarcomas, having GD (arm B) as an internal control In parallel translational studies will be performed to identify factors predictive of the activity of T in this specific histotype.

Condition or disease Intervention/treatment Phase
Leiomyosarcoma Drug: gemcitabine + docetaxel Drug: trabectedin Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 168 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Randomized - Non Comparative - Study on the Activity of Trabectedin or Gemcitabine + Docetaxel in Metastatic or Locally Relapsed Uterine Leiomyosarcoma Pretreated With Conventional Chemotherapy
Study Start Date : April 2010
Actual Primary Completion Date : April 30, 2017
Actual Study Completion Date : April 30, 2017

Arm Intervention/treatment
Experimental: Trabectedin
Trabectedin 1.3 mg/m2 will be administered via a central venous catheter as a 24-hour infusion on day 1 of 21-days treatment cycles. Trabectedin treatment can be continued until progressive disease, major toxicity, patient's intolerance or unwillingness to continue treatment or medical decision by the responsible physician.
Drug: trabectedin
Other Name: Yondelis

Active Comparator: gemcitabine + docetaxel
Gemcitabine 900 mg/m2 will be administered via a central venous catheter on days one and eight over 90 min, followed by docetaxel 75 mg/m2 on day eight iv over 1 h. Gemcitabine+docetaxel treatment is planned for six cycles, unless there is evidence of disease progression, unacceptable toxicity or patient's intolerance or unwillingness to continue treatment, or medical decision by the responsible physician. Patients with continued response after six cycles can receive two additional cycles of combination therapy or continue with Gemcitabine alone.
Drug: gemcitabine + docetaxel
Other Names:
  • Gemzar
  • Taxotere

Primary Outcome Measures :
  1. progression free rate at 6-month [ Time Frame: 6-month ]
    Primary objective will be to assess the clinical benefit rate (defined as 6-month progression free rate) with trabectedin in patients with locally relapsed/metastatic uterine leiomyosarcoma pretreated with anthracycline ± ifosfamide and/or gemcitabine ± docetaxel.

Secondary Outcome Measures :
  1. best response rate [ Time Frame: within 6 months ]
    response rate according to RECIST v1.0 criteria

Other Outcome Measures:
  1. progression free survival [ Time Frame: 24 months ]
    Time from inclusion into the study to progression or death whichever comes first

  2. Overall survival [ Time Frame: 24 months ]
    time from inclusion into the study to death from any cause

  3. safety profile [ Time Frame: up to 30 days after the end of treatments ]
    Number of Patients with Serious and Non-Serious Adverse Events

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically proven uterine leiomyosarcoma.
  2. Persistent or locally relapsed and/or metastatic disease.
  3. At least one previous systemic treatment with an anthracycline ± ifosfamide or gemcitabine ± docetaxel.
  4. Measurable disease, as defined by RECIST criteria.
  5. ECOG PS <=2.
  6. Age >= 18 years.
  7. A minimum of 3 weeks since prior tumor directed therapy
  8. Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or lower.
  9. Adequate haematological function.
  10. Adequate renal function.
  11. Adequate liver function.
  12. Signed informed consent.

Exclusion Criteria:

  1. Prior exposure to Trabectedin.
  2. Peripheral neuropathy, Grade 2 or higher.
  3. History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission from 5 years or more and judged of negligible potential of relapse.
  4. Known CNS metastases.
  5. Active viral hepatitis or chronic liver disease.
  6. Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias.
  7. Active major infection.
  8. Other serious concomitant illnesses

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02249702

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Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
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Principal Investigator: Angiolo Gadducci, MD Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
Principal Investigator: Federica Grosso, MD Azienda Ospedaliera Alessandria, Italy

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Responsible Party: Mario Negri Institute for Pharmacological Research Identifier: NCT02249702    
Other Study ID Numbers: TAUL
2009-016017-24 ( EudraCT Number )
First Posted: September 25, 2014    Key Record Dates
Last Update Posted: December 6, 2017
Last Verified: December 2017
Keywords provided by Mario Negri Institute for Pharmacological Research:
uterine leiomyosarcoma
Additional relevant MeSH terms:
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Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Alkylating
Alkylating Agents