Phase II Study of Liarozole Fumarate for Unresectable or Metastatic Breast Cancer (Summary Last Modified 07/98)

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Alternate Title

Liarozole in Treating Women With Unresectable or Metastatic Breast Cancer

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IITreatmentClosedpostmenopausalEORTC-10941


I.  Evaluate whether partial or complete responses can be achieved with 
liarozole fumarate in patients with advanced breast cancer.

II.  Assess the probability of an actual response rate warranting further 
evaluation of therapeutic effectiveness in the event of partial or complete 
responses to liarozole fumarate in this patient population.

III.  Characterize the safety and tolerance to liarozole fumarate in these 

Entry Criteria

Disease Characteristics:

Histologically or cytologically verified breast cancer that is unresectable or
metastatic in the following hormone receptor/prior therapy categories:
  ER positive, tamoxifen-refractory, i.e.:
     Relapsed on adjuvant tamoxifen within 1 year of beginning treatment OR
     Clearly progressive within 4 months of beginning tamoxifen as first-line
        therapy for recurrent disease

  ER negative:
     Maximum of 1 prior regimen for metastatic disease (chemotherapy or
        hormonal therapy)
     Prior adjuvant chemotherapy or hormonal therapy allowed

  ER positive or unknown that has shown benefit to 1 or 2 prior hormonal
  therapies (including tamoxifen), i.e.:
     Prior objective response to hormonal therapy
     No change during at least 6 months of endocrine therapy
     Disease-free for at least 1 year (for ER positive) or 2 years (for ER
        unknown) following adjuvant hormonal therapy (adjuvant chemotherapy

  Hormone receptor status should be measured at study entry (if more than 1
  value is available, status is determined by the most recent one obtained
  while off hormonal therapy)
     ER-positive defined as at least 10 femtomoles/mg cytosol protein

Uni- or bidimensionally measurable disease required, e.g.:
  Skin nodule
  Lung lesion at least 15 mm and completely or partially surrounded by aerated
  Lytic bone lesion at least 10 mm in 2 diameters or at least 15 mm in 1
     diameter and assessable by conventional x-ray, CT, or MRI
  Abdominal or soft tissue mass that is palpable and measurable
  Mediastinal or hilar involvement in which normal width (preinvolvement) can
     be subtracted from pretreatment width on chest x-ray
  Irregular skin metastases and lymphangitic cutaneous spread ("cancer en
     cuirasse") with adequate clinical photograph
  Liver lesion at least 20 mm in 2 diameters or 25 mm in 1 diameter on CT
  New lesion in previously irradiated field

The following are not considered uni- or bidimensionally measurable but may be
used in overall assessment:
  Previously irradiated lesion
  Pleural effusion
  Osteoblastic or mixed bone metastases
  Abdominal lesion that is palpable but not measurable

The following are not acceptable as sole manifestation of disease:
  Pleural effusion
  Osteoblastic skeletal lesions
  Liver metastases as sole site of recurrent disease

No brain or leptomeningeal metastases

No rapidly progressing, life-threatening metastases

Prior/Concurrent Therapy:

See Disease Characteristics
Recovery from prior therapy required
Prior radiotherapy allowed (no delay prior to entry)
No concurrent experimental drugs or steroids

Patient Characteristics:

  Any age

  Females only

Menopausal status:
  Postmenopausal, i.e.:
     Amenorrheic for at least 12 months regardless of age
     Amenorrheic and age 56 or over
     Serum FSH and estradiol levels within normal menopausal range on 2
        determinations at least 1 week apart (at least 4 weeks after cessation
        of oral contraceptives)

Performance status:
  WHO 0-3

Life expectancy:
  At least 3 months

  WBC at least 3,000
  Platelets at least 100,000

  Bilirubin no greater than 1.5 mg/dL (25 micromoles/L)
  AST no greater than twice normal (3 times normal if liver metastases)

  Creatinine no greater than 2.0 mg/dL (175 micromoles/L)

  No active uncontrolled infection
  No poor medical risk due to nonmalignant systemic disease
  No prior or current second malignancy except:
     Primary breast cancer
     Adequately treated basal cell skin cancer
     Adequately treated localized squamous cell skin cancer
     Cone-biopsied in situ cervical cancer
  No pregnant or nursing women

Expected Enrollment

Up to 29 patients will be accrued.  If no response is seen in the first 16 
patients, accrual will cease.


All patients receive liarozole fumarate daily by mouth for at least 8 weeks.  
The dose may be increased once after 2 weeks if treatment is well tolerated.  
Therapy may continue until disease progression outside the brain intervenes.

Radiotherapy to nonindicator lesions for palliation of painful bone metastases 
is allowed.  No concomitant investigational drugs are allowed.

Patients are assessed for response every 8 weeks and followed for survival.

Published Results

Hamilton A, Roy JA, Beex L, et al.: EORTC 10941: A phase II study of liarozole in postmenopausal patients with 'chemotherapy-resistant' or 'potentially hormone sensitive' metastatic breast cancer. Breast Cancer Res Treat 60 (2): 181-8, 2000.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Jan Klijn, MD, PhD, Protocol chair
Ph: 31-10-439-1733

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.