Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

E7389 in Treating Patients With Advanced and/or Metastatic Soft Tissue Sarcoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Active	18 and over	Other, Pharmaceutical / Industry	EORTC-62052 EISAI-E7389-E044-207, EUDRACT-2005-004272-20, NCT00413192

Objectives

Primary

1. Evaluate the therapeutic activity and safety of E7389 in patients with recurrent or refractory, advanced and/or metastatic soft tissue sarcoma.
2. Assess the plasma concentration-time course after treatment with this drug in these patients.

Secondary

1. Determine covariate relationships for pharmacokinetic parameters.
2. Determine pharmacokinetic/pharmacodynamic relationships for efficacy and safety.

Entry Criteria

Disease Characteristics:

• Histologically confirmed soft tissue sarcoma of high or intermediate grade, including 1 of the following histologies:
  • Leiomyosarcoma
  • Adipocytic tumors (liposarcoma dedifferentiated, myxoid/round cell, pleomorphic, mixed-type, or not otherwise specified)
  • Synovial sarcoma
  • Fibroblastic tumors (adult fibrosarcoma, myxofibrosarcoma, sclerosing epithelioid fibrosarcoma)
  • So-called fibrohistiocytic tumors (pleomorphic malignant fibrous histiocytoma [MFH], giant cell MFH, or inflammatory MFH)
  • Malignant glomus tumors
  • Skeletal muscle tumors (rhabdomyosarcoma, alveolar, or pleomorphic), excluding embryonal rhabdomyosarcoma
  • Vascular tumors (epithelioid hemangioendothelioma or angiosarcoma)
  • Tumors of uncertain differentiation (synovial, epithelioid, alveolar soft part, clear cell, desmoplastic small round cell, extrarenal rhabdoid, malignant mesenchymoma, perivascular epithelioid cell tumor, or intimal sarcoma), excluding chondrosarcoma, Ewing's tumor/primitive neuroectodermal tumor (PNET)
  • Malignant peripheral nerve sheath tumors
  • Malignant solitary fibrous tumors
  • Undifferentiated soft tissue sarcomas not otherwise specified
  • Other types of sarcoma



• The following tumor types are not eligible:
  • Embryonal rhabdomyosarcoma
  • Chondrosarcoma
  • Osteosarcoma
  • Ewing's tumors/ PNET
  • Gastrointestinal stromal tumors
  • Dermatofibrosarcoma protuberans
  • Inflammatory myofibroblastic sarcoma
  • Neuroblastoma
  • Malignant mesothelioma
  • Mixed mesodermal tumors of the uterus



• Advanced and/or metastatic disease
  • Recurrent or refractory disease and/or metastatic disease incurable by surgery or radiotherapy



• Measurable disease



• Objective progression within the past 6 months, defined as appearance of new lesions OR increase of 20% in the sum of the diameters of measurable lesions
  • Progression of nonmeasurable lesions to be confirmed by an external review
  • No other specific treatments since progression



• No brain or subdural metastases unless the following are true:
  • Local therapy was completed
  • Discontinued corticosteroids at least 4 weeks ago
  • Any signs (e.g., radiologic) and/or symptoms of brain metastases must be stable for at least 4 weeks



• Formalin fixed paraffin-embedded tumor blocks and representative hematoxylin/eosin slides must be available

Prior/Concurrent Therapy:

• See Disease Characteristics
• Recovered from all prior therapy
• No prior participation in another E7389 study
• No more than 1 combination regimen or 2 single-agent chemotherapy regimens for advanced disease
  • Neoadjuvant or adjuvant therapy does not count towards this requirement
• More than 28 days since prior major surgery
• More than 28 days since prior hormonal therapy (other than replacement therapy)
• More than 28 days since prior chemotherapy, radiotherapy, or immunotherapy
• More than 28 days since prior and no other concurrent investigational agents
• Concurrent corticosteroids, including prednisone, and bisphosphonates allowed provided dose has been stable for ≥ 2 weeks
• No concurrent gene therapy or tyrosine kinase inhibitors
• No concurrent anticoagulant therapy with warfarin or related compounds
  • Mini-dose warfarin or heparin-based line patency allowed
• No concurrent anticancer therapy, including chemotherapy, hormone therapy, tyrosine kinase inhibitors, or immunotherapy

Patient Characteristics:

• WHO performance status 0-1
• Absolute neutrophil count > 1,500/mm³
• Platelet count > 100,000/mm³
• Bilirubin < 1.5 mg/dL
• AST and ALT ≤ 3 times upper limit of normal (ULN) (< 5 times ULN for liver metastases)
• Creatinine < 2.0 mg/dL OR creatinine clearance > 40 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No pre-existing neuropathy > grade 2
• No other malignancies within the past 3 years except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast
• No significant cardiovascular impairment, including any of the following:
  • New York Heart Association class II-IV congestive heart failure
  • Unstable angina or myocardial infarction within the past 6 months
  • Serious cardiac arrhythmias
• No severe or uncontrolled intercurrent illness or infection
• No known hypersensitivity to halichondrin B and/or halicondrin B chemical derivative
• No psychological, familial, sociological, or geographical condition that would preclude study compliance

Expected Enrollment

A total of 148 patients will be accrued for this study.

Outcomes

12-week progression-free survival

Overall progression-free survival
Objective response (complete response [CR] and partial response [PR])
Clinical response benefit (CR, PR, stable disease)
Time to onset of response
Duration of response
Safety
Overall survival

Outline

This is an open-label, nonrandomized, multicenter study. Patients are stratified according to soft tissue sarcoma type (leiomyosarcoma vs adipocytic tumors vs synovial sarcoma vs other soft tissue sarcoma types).

Patients receive E7389 IV over 2-5 minutes on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected during course 1 and are evaluated for pharmacokinetic analysis.

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

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Patrick Schoffski, MD, MPH, Study coordinator		Ph: 32-1634-6916 Email: patrick.schoffski@uz.kuleuven.be

Belgium
	Leuven
	U.Z. Gasthuisberg
		Contact Person	Ph:  32-1634-6916

Registry Information
Official Title		Phase II Study E7389 of Administered as an IV Infusion Day 1 and 8 Every 3 Weeks in Pretreated in Patients with Advanced and/or Metastatic Soft Tissue Sarcoma
Trial Start Date		2006-12-20
Registered in ClinicalTrials.gov		NCT00413192
Date Submitted to PDQ		2007-01-08
Information Last Verified		2007-04-12

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