E7389 Administered as an IV Bolus Infusion Day 1 and Day 8 Every 3 Weeks in Pre-Treated Patients With Advanced and/or Metastatic Soft Tissue Sarcoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00413192
First received: December 15, 2006
Last updated: June 30, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to evaluate the therapeutic activity and safety of E7389 in patients with advanced/metastatic soft tissue sarcoma who have failed standard chemotherapy.


Condition Intervention Phase
Soft Tissue Sarcoma
Drug: E7389
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of E7389 Administered as an IV Bolus Infusion Day 1 and Day 8 Every 3 Weeks in Pre-Treated Patients With Advanced and/or Metastatic Soft Tissue Sarcoma

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Progression free survival at 12 weeks after the start of treatment according to Response Evaluation Criteria In Solid Tumors (RECIST). [ Time Frame: 12 weeks. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival, overall progression free survival, objective response, clinical response benefit, time to onset of response, duration of response, safety profile. [ Time Frame: End of study. ] [ Designated as safety issue: Yes ]

Enrollment: 128
Study Start Date: January 2007
Study Completion Date: February 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: E7389
1.4 mg/m^2 administered as an intravenous (I.V.) bolus infusion on Days 1 and 8 of every 21 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically proven advanced and/or metastatic malignant soft tissue sarcoma of high or intermediate grade, and of one of the following histologies (World Health Organization (WHO) classification 2002):

    • Leiomyosarcoma
    • Adipocytic (liposarcoma dedifferentiated, myxoid/round cell, pleomorphic, mixed-type not otherwise specified)
    • Synovial sarcoma
    • Other types of sarcoma, including:
    • Fibroblastic (adult fibrosarcoma, myxofibrosarcoma, sclerosing epithelioid fibrosarcoma).
    • So-called fibrohistiocytic (pleomorphic Malignant Fibrous Histiocytoma (MFH), giant cell "MFH", inflammatory "MFH")
    • Malignant glomus tumors.
    • Skeletal muscles (rhabdomyosarcoma, alveolar or pleomorphic) excluding embryonal rhabdomyosarcoma.
    • Vascular (epithelioid haemangioendothelioma, angiosarcoma).
    • Uncertain differentiation (synovial, epithelioid, alveolar soft part, clear cell, desmoplastic small round cell, extra-renal rhabdoid, malignant mesenchymoma, perivascular epithelioid cell tumor (PEComa), intimal sarcoma) excluding chondrosarcoma, Ewing tumors / Primitive neuroectodermal tumor (PNET)
    • Malignant peripheral nerve sheath tumors.
    • Malignant solitary fibrous tumors.
    • Undifferentiated soft tissue sarcomas not otherwise specified.
    • Other types of sarcoma (not listed as not eligible), if approved by the Study Coordinator (written or e-mail approval needed prior to registration).
    • The following tumor types are not eligible:
    • Embryonal rhabdomyosarcoma
    • Chondrosarcoma
    • Osteosarcoma
    • Ewing tumors / PNET
    • Gastro-intestinal stromal tumors (GIST)
    • Dermatofibrosarcoma protuberans
    • Inflammatory myofibroblastic sarcoma
    • Neuroblastoma
    • Malignant mesothelioma
    • Mixed mesodermal tumors of the uterus
  2. Formalin fixed paraffin embedded tumor blocks and representative H/E (hematoxylin/eosin) slides must be available for histological central review. Histological central review is not required before treatment start but is mandatory within 10 days of registration. Local histopathological diagnosis will be accepted for entry into the study.
  3. Relapsed, refractory and/or metastatic disease incurable by surgery or radiotherapy.
  4. Evidence of objective progression within the last 6 months (RECIST) documented by measurements of disease, i.e. appearance of new lesions, increase of 20% in the sum of the diameters of measurable lesions, or progression of non measurable lesions to be confirmed by an external review, without other specific treatment since objective documentation of progression.
  5. Presence of measurable disease, as defined by RECIST.
  6. Patients must have received no more than one combination or two single agent chemotherapy regimens for advanced disease; (neo)adjuvant therapy is not counted towards this requirement.
  7. No major surgery, hormonal therapy (other than replacement), chemotherapy or radiotherapy, immunotherapy or other investigational agent within the last 28 days and/or not recovered from prior therapy within the last 28 days. Use of erythropoietin is considered supportive care and is permitted.
  8. Absence of brain or subdural metastases, unless patient has completed local therapy and has discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment with E7389. Any signs (e.g., radiologic) and/or symptoms of brain metastases must be stable for at least 4 weeks.
  9. Absence of pre-existing neuropathy > Grade 2
  10. At least 18 years of age.
  11. WHO performance status 0 or 1.
  12. Adequate bone marrow function (absolute neutrophil count >1.5 x 109/L, platelets >100 x 109/L)
  13. Adequate hepatic function (bilirubin < 1.5 mg/mL or 25 µmol/L, SGOT/AST and SGPT/ALT <= 3 x UNL or < 5 x UNL in patients with liver metastases).
  14. Adequate renal function: serum creatinine < 2.0 mg/dl or 177 µmol/l or calculated (Cockcroft and Gault formula) creatinine clearance > 40 ml/min.
  15. Women should either not be of childbearing potential (having had a hysterectomy, a bilateral oophorectomy or bilateral tubal ligation, or be post-menopausal with a total cessation of menses of >1 year), or not be pregnant (negative serum pregnancy test at entry), should not be lactating, should agree to use contraceptive methods (with a documented failure rate < 1%, vasectomized partner sterile prior to trial entry and sole sexual partner or double-barrier contraception) while on treatment and during a period of 3 months after the end of treatment. Sexually active male participants must use barrier methods of contraception.
  16. Before patient registration/randomization, written informed consent must be given according to International Conference on Harmonization/Good Clinical Practice (ICH/GCP), and national/local regulations.

Exclusion Criteria:

  1. Prior history of malignancies other than sarcoma (except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or the patient has been free of any other malignancies for > 3 years).
  2. Significant cardiovascular impairment (history of congestive heart failure > New York Heart Association (NYHA) grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia).
  3. Patients who are receiving anti-coagulant therapy with warfarin or related compounds, other than for line patency, and cannot be changed to heparin-based therapy, are not eligible. If a patient is to continue on mini-dose warfarin, then the prothrombin time (PT) / international normalized ratio (INR) must be closely monitored.
  4. Severe/uncontrolled intercurrent illness/infection.
  5. Patients with a known hypersensitivity to halichondrin B and/or halichondrin B chemical derivative.
  6. Patients who participated in a prior E7389 clinical trial.
  7. Patients without freedom (by the law or administrative decision), hospitalized without their consent (mental disability, upon legal request), admitted in medical or social establishment for other reasons than clinical research, with any psychological, familial, sociological, geographical condition potentially hampering compliance with the study protocol and follow-up schedule ; those conditions should be assessed with the patient before registration in the trial.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00413192

Locations
Belgium
Brussels, Belgium, BE 1000
Leuven, Belgium, BE 3000
Denmark
Aarhus, Denmark, DK 8000
Herlev, Denmark, DK 2730
France
Bordeaux, France, 33076
Lyon, France, 69008
Marseille, France, 13385
Villejuif, France, 94805
Germany
Bad Saarow, Germany, 15526
Dresden, Germany, DE 01307
Essen, Germany, DE 45122
Hannover, Germany, DE 30625
Mannheim, Germany, DE 68135
Tuebingen, Germany, DE 72076
Poland
Warsaw, Poland, 02 781
Sponsors and Collaborators
Eisai Inc.
  More Information

No publications provided by Eisai Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00413192     History of Changes
Other Study ID Numbers: E7389-E044-207, 2005-004272-20
Study First Received: December 15, 2006
Last Updated: June 30, 2014
Health Authority: European Union: European Medicines Agency

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on October 19, 2014