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Brostallicin or Doxorubicin as First-Line Therapy in Treating Patients With Relapsed, Refractory, or Metastatic Soft Tissue Sarcoma

Primary Purpose

Ovarian Cancer, Sarcoma, Small Intestine Cancer

Status
Unknown status
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
brostallicin
doxorubicin hydrochloride
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring recurrent adult soft tissue sarcoma, stage IV adult soft tissue sarcoma, adult liposarcoma, adult fibrosarcoma, adult malignant fibrous histiocytoma, adult leiomyosarcoma, adult rhabdomyosarcoma, adult alveolar soft-part sarcoma, adult malignant mesenchymoma, adult angiosarcoma, adult epithelioid sarcoma, adult neurofibrosarcoma, adult synovial sarcoma, recurrent uterine sarcoma, stage IV uterine sarcoma, ovarian sarcoma, small intestine leiomyosarcoma, recurrent small intestine cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed high- or intermediate-grade malignant soft tissue sarcoma* of 1 of the following cellular types:

    • Adipocytic (e.g., liposarcoma dedifferentiated, myxoid/round cell, pleomorphic, mixed-type, not otherwise specified)
    • Fibroblastic (e.g., adult fibrosarcoma, myxofibrosarcoma, or sclerosing epithelioid fibrosarcoma)
    • So-called fibrohistiocytic (e.g., pleomorphic malignant fibrous histiocytoma [MFH], giant cell MFH, or inflammatory MFH)
    • Leiomyosarcoma
    • Malignant glomus tumors
    • Skeletal muscle (e.g., rhabdomyosarcoma, alveolar, or pleomorphic)
    • Vascular (e.g., epithelioid hemangioendothelioma or angiosarcoma)
    • Uncertain differentiation (e.g., synovial, epithelioid, alveolar soft part, clear cell, desmoplastic small round cell, extra-renal rhabdoid, malignant mesenchymoma, perivascular epithelioid cell tumor [PEComa], or intimal sarcoma)
    • Malignant peripheral nerve sheath tumors
    • Malignant solitary fibrous tumors
    • Undifferentiated soft tissue sarcomas not otherwise specified
    • Other types of sarcoma if approved by the study coordinator NOTE: *Includes malignant tumors of non-organ origin and skin and uterine leiomyosarcoma
  • The following tumor types are excluded:

    • Embryonal rhabdomyosarcoma
    • Chondrosarcoma
    • Osteosarcoma
    • Ewing tumors/primitive neuroectodermal tumor (PNET)
    • Gastrointestinal stromal tumors
    • Dermatofibrosarcoma protuberans
    • Inflammatory myofibroblastic sarcoma
    • Neuroblastoma
    • Malignant mesothelioma
    • Mixed mesodermal tumors of the uterus
  • Relapsed, refractory, and/or metastatic disease incurable by surgery or radiotherapy
  • Measurable disease
  • Must have formalin fixed paraffin-embedded tumor blocks and representative hematoxylin/eosin slides available for histological central review
  • No symptomatic or known CNS metastases

PATIENT CHARACTERISTICS:

  • At least 60 years of age OR ≥ 18 years of age if patient is not suitable for intensive combination chemotherapy treatments
  • WHO performance status 0-1
  • Absolute neutrophil count > 2,000/mm³
  • Platelet count > 100,000/mm³
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Creatinine clearance ≥ 60 mL/min
  • No serious cardiac illness within the past 6 months, including, but not limited to the following:

    • History of documented congestive heart failure
    • High-risk uncontrolled arrhythmias
    • Angina pectoris requiring antianginal medication
    • Clinically significant valvular heart disease
    • Evidence of transmural infarction on ECG
    • Poorly-controlled hypertension (e.g., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg)
  • Normal 12-lead ECG
  • LVEF normal by MUGA or echocardiogram
  • No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
  • No other serious and/or unstable medical condition, illness, or lab abnormality that would preclude study participation
  • No psychiatric illness or familial, social, or geographical condition that would preclude study compliance
  • No active uncontrolled infection
  • No known AIDS positivity
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy regimen for advanced or metastatic disease (neoadjuvant and adjuvant therapy allowed)
  • No concurrent sargramostim (GM-CSF) except in cases of febrile neutropenia
  • No other concurrent anticancer therapy or investigational agents, including any of the following:

    • Chemotherapy
    • Biological response modifiers
    • Hormone therapy
    • Immunotherapy
  • No other concurrent clinical treatment trial participation

Sites / Locations

  • Leiden University Medical Center

Outcomes

Primary Outcome Measures

Six-month progression-free survival, in terms of complete response, partial response, or no change

Secondary Outcome Measures

Overall progression-free survival
Objective tumor response
Safety (CTCAE v 3.0)
Duration of response
Overall survival

Full Information

First Posted
December 11, 2006
Last Updated
August 7, 2014
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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1. Study Identification

Unique Protocol Identification Number
NCT00410462
Brief Title
Brostallicin or Doxorubicin as First-Line Therapy in Treating Patients With Relapsed, Refractory, or Metastatic Soft Tissue Sarcoma
Official Title
Randomized Phase II Study of Brostallicin (PNU-166196A) Versus Doxorubicin as First Line Chemotherapy in Patients With Advanced or Metastatic Soft Tissue Sarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2010
Overall Recruitment Status
Unknown status
Study Start Date
October 2006 (undefined)
Primary Completion Date
September 2008 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy, such as brostallicin and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This randomized phase II trial is studying the side effects and how well brostallicin or doxorubicin works as first-line therapy in treating patients with relapsed, refractory, or metastatic soft tissue sarcoma.
Detailed Description
OBJECTIVES: Primary Determine the activity and safety of brostallicin vs doxorubicin hydrochloride as first-line therapy in patients with relapsed, refractory, or metastatic soft tissue sarcoma. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating and age(younger than 60 years vs 60 years and over). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive brostallicin IV over 10 minutes on day 1. Arm II: Patients receive doxorubicin hydrochloride IV over 10 minutes on day 1. In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter. PROJECTED ACCRUAL: A total of 108 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Sarcoma, Small Intestine Cancer
Keywords
recurrent adult soft tissue sarcoma, stage IV adult soft tissue sarcoma, adult liposarcoma, adult fibrosarcoma, adult malignant fibrous histiocytoma, adult leiomyosarcoma, adult rhabdomyosarcoma, adult alveolar soft-part sarcoma, adult malignant mesenchymoma, adult angiosarcoma, adult epithelioid sarcoma, adult neurofibrosarcoma, adult synovial sarcoma, recurrent uterine sarcoma, stage IV uterine sarcoma, ovarian sarcoma, small intestine leiomyosarcoma, recurrent small intestine cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Allocation
Randomized
Enrollment
118 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
brostallicin
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Primary Outcome Measure Information:
Title
Six-month progression-free survival, in terms of complete response, partial response, or no change
Secondary Outcome Measure Information:
Title
Overall progression-free survival
Title
Objective tumor response
Title
Safety (CTCAE v 3.0)
Title
Duration of response
Title
Overall survival

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed high- or intermediate-grade malignant soft tissue sarcoma* of 1 of the following cellular types: Adipocytic (e.g., liposarcoma dedifferentiated, myxoid/round cell, pleomorphic, mixed-type, not otherwise specified) Fibroblastic (e.g., adult fibrosarcoma, myxofibrosarcoma, or sclerosing epithelioid fibrosarcoma) So-called fibrohistiocytic (e.g., pleomorphic malignant fibrous histiocytoma [MFH], giant cell MFH, or inflammatory MFH) Leiomyosarcoma Malignant glomus tumors Skeletal muscle (e.g., rhabdomyosarcoma, alveolar, or pleomorphic) Vascular (e.g., epithelioid hemangioendothelioma or angiosarcoma) Uncertain differentiation (e.g., synovial, epithelioid, alveolar soft part, clear cell, desmoplastic small round cell, extra-renal rhabdoid, malignant mesenchymoma, perivascular epithelioid cell tumor [PEComa], or intimal sarcoma) Malignant peripheral nerve sheath tumors Malignant solitary fibrous tumors Undifferentiated soft tissue sarcomas not otherwise specified Other types of sarcoma if approved by the study coordinator NOTE: *Includes malignant tumors of non-organ origin and skin and uterine leiomyosarcoma The following tumor types are excluded: Embryonal rhabdomyosarcoma Chondrosarcoma Osteosarcoma Ewing tumors/primitive neuroectodermal tumor (PNET) Gastrointestinal stromal tumors Dermatofibrosarcoma protuberans Inflammatory myofibroblastic sarcoma Neuroblastoma Malignant mesothelioma Mixed mesodermal tumors of the uterus Relapsed, refractory, and/or metastatic disease incurable by surgery or radiotherapy Measurable disease Must have formalin fixed paraffin-embedded tumor blocks and representative hematoxylin/eosin slides available for histological central review No symptomatic or known CNS metastases PATIENT CHARACTERISTICS: At least 60 years of age OR ≥ 18 years of age if patient is not suitable for intensive combination chemotherapy treatments WHO performance status 0-1 Absolute neutrophil count > 2,000/mm³ Platelet count > 100,000/mm³ Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Creatinine clearance ≥ 60 mL/min No serious cardiac illness within the past 6 months, including, but not limited to the following: History of documented congestive heart failure High-risk uncontrolled arrhythmias Angina pectoris requiring antianginal medication Clinically significant valvular heart disease Evidence of transmural infarction on ECG Poorly-controlled hypertension (e.g., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg) Normal 12-lead ECG LVEF normal by MUGA or echocardiogram No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast No other serious and/or unstable medical condition, illness, or lab abnormality that would preclude study participation No psychiatric illness or familial, social, or geographical condition that would preclude study compliance No active uncontrolled infection No known AIDS positivity Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: No prior chemotherapy regimen for advanced or metastatic disease (neoadjuvant and adjuvant therapy allowed) No concurrent sargramostim (GM-CSF) except in cases of febrile neutropenia No other concurrent anticancer therapy or investigational agents, including any of the following: Chemotherapy Biological response modifiers Hormone therapy Immunotherapy No other concurrent clinical treatment trial participation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans Gelderblom, MD, PhD
Organizational Affiliation
Leiden University Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2300 RC
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
24215845
Citation
Gelderblom H, Blay JY, Seddon BM, Leahy M, Ray-Coquard I, Sleijfer S, Kerst JM, Rutkowski P, Bauer S, Ouali M, Marreaud S, van der Straaten RJ, Guchelaar HJ, Weitman SD, Hogendoorn PC, Hohenberger P. Brostallicin versus doxorubicin as first-line chemotherapy in patients with advanced or metastatic soft tissue sarcoma: an European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group randomised phase II and pharmacogenetic study. Eur J Cancer. 2014 Jan;50(2):388-96. doi: 10.1016/j.ejca.2013.10.002. Epub 2013 Nov 8.
Results Reference
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Brostallicin or Doxorubicin as First-Line Therapy in Treating Patients With Relapsed, Refractory, or Metastatic Soft Tissue Sarcoma

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