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ZK 230211 in Postmenopausal Woman With Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00555919
First received: November 8, 2007
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

Randomized phase II study to investigate the efficacy, safety and tolerability of ZK 230211 (100 mg vs. 25 mg) as second-line endocrine therapy for postmenopausal women with hormone receptor-positive metastatic breast cancer.Once the cancer has spread beyond the lymph nodes to areas such as e.g. the skin, soft tissues, lung, and liver it is called metastatic breast cancer. Patients who have been diagnosed with metastatic breast cancer that has progressed since their previous cancer treatment and that cannot be removed completely by surgery are eligible to be treated within this trial.Treatment with a new drug called Progesterone Receptor Antagonist ZK 230211 (ZK PRA) targets the progesterone receptor which may be expressed on breast cancer tumour cells. Therefore only patients with this progesterone receptor on their tumour cells can be included in this study.Progesterone receptor antagonists (including onapristone) have already shown efficacy in postmenopausal women with advanced breast cancer (Klijn et al. 2000). This phase II study investigates the efficacy (proof of concept), safety and tolerability of ZK PRA at two dose levels (25 mg and 100 mg) before initiating pivotal phase III trials.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: Lonaprisan (ZK 230211, BAY86-5044)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study to Investigate the Efficacy, Safety and Tolerability of ZK 230211 (25 mg vs. 100 mg) as Second-line Endocrine Therapy for Postmenopausal Women With Hormone Receptor-positive Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • To evaluate efficacy (clinical benefit) of two doses of ZK PRA (25 mg and 100 mg) when administered once daily p.o. [ Time Frame: month 3, month 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate safety and tolerability [ Time Frame: ongoing thoughout the trial ] [ Designated as safety issue: Yes ]
  • To evaluate the pharmacokinetics of ZK PRA [ Time Frame: baseline, month1,2,6 ] [ Designated as safety issue: No ]
  • To evaluate the effect of ZK PRA on quality of life (QoL) [ Time Frame: baseline, month 1,2,3,4,5,6 ] [ Designated as safety issue: No ]
  • To perform exploratory analysis of biomarkers [ Time Frame: baseline, month 1, 3 ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • Objective response rate (ORR) / Duration of response - in the subset of patients with measurable disease [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • Duration of Clinical Benefit [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: end of study ] [ Designated as safety issue: No ]

Enrollment: 68
Study Start Date: March 2008
Study Completion Date: March 2011
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: Lonaprisan (ZK 230211, BAY86-5044)
25 mg daily oral treatment
Experimental: Arm 2 Drug: Lonaprisan (ZK 230211, BAY86-5044)
100 mg daily oral treatment

  Eligibility

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

Inclusion Criteria:

  • Postmenopausal women defined as: aged >/= 50 years with amenorrhea for at least 12 months or aged < 50 years with 6 months of spontaneous amenorrhea and follicle stimulating hormone (FSH) level within postmenopausal range (> 40 mIU/ml) or having undergone bilateral oophorectomy
  • Histologically or cytologically confirmed breast cancer
  • Metastatic breast cancer (Stage IV according to UICC - Union Internationale Contre Cancer - criteria, Version 6)
  • Progesterone receptor-positive tumors
  • Patients must be considered candidates for endocrine therapy (no other therapies for breast cancer are required)
  • Disease progression after first-line endocrine therapy for advanced breast cancer (i.e. with tumor remission or stabilization lasting at least 3 months under endocrine therapy)
  • At least one measurable or non-measurable tumor lesion (according to RECIST criteria)
  • WHO Performance status 1
  • Adequate function of major organs and systems:

    • Hematopoietic:

      • Hemoglobin: 10 g/dL
      • Absolute neutrophil count: 1,500/mm3
      • Platelet count: 100,000/mm3
    • Hepatic:

      • Total bilirubin: 1.5 times the upper limit of normal
      • AST/ALT: 2.5 times the upper limit of normal
    • Renal: Creatinine: 1.5 times the upper limit of normal
    • Gynecological: Endometrial thickness (in non-hysterectomized women) </= 10 mm double layer
    • No other uncontrolled concurrent illness
  • Adequate recovery from previous surgery, radiation and chemotherapy
  • Written informed consent

Exclusion Criteria:

  • Presence of any of the following conditions:

    • life-threatening metastatic visceral disease (extensive hepatic involvement)
    • any metastases to the central nervous system (CNS)
    • pulmonary lymphangitic metastases involving more than 50% of the lung
  • More than one prior endocrine treatment for advanced breast cancer
  • Previous combination of endocrine treatment with any other type of treatment (except chemotherapy), or previous sequential endocrine treatments (if there was disease progression between treatments) are not permitted in this trial.
  • Patients with breast cancer HER-2 positive or with unknown HER-2 status are not eligible.
  • Malignancies or history of prior malignancy other than carcinoma in situ of the cervix or uterus, or basal and squamous cell carcinoma of the skin
  • Intake of CYP3A4 inhibitors less than 2 weeks before start of study treatment
  • A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds (ms)
  • A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
  • The use of concomitant medications that prolong the QT/QTc interval
  • Other investigational drug therapies less than 4 weeks or at least 5 half-lives before start of study treatment (less than 4 weeks for faslodex and less than 2 weeks for any other endocrine therapy)
  • Expectation that the patient will not be able to complete at least 3 months of therapy
  • Unwillingness or inability to comply with the protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00555919

Locations
Austria
Graz, Austria, 8036
Innsbruck, Austria, 6020
Salzburg, Austria, 5020
Wien, Austria, 1100
Finland
Turku, Finland, FIN-20521
Vaasa, Finland, 65130
France
Lille, France, 59020
Lyon Cedex, France, 69008
Montpellier, France, 34000
Nantes, France, 44805
Paris, France, 75020
Reims, France, 51056
Germany
Tübingen, Baden-Württemberg, Germany, 72076
Erlangen, Bayern, Germany, 91054
Frankfurt, Hessen, Germany, 60590
Rostock, Mecklenburg-Vorpommern, Germany, 18059
Kiel, Schleswig-Holstein, Germany, 24105
Italy
Rozzano, Milano, Italy, 20089
Poland
Bialystok, Poland, 15-540
Gdansk, Poland, 80-219
Olsztyn, Poland, 10-226
Poznan, Poland, 60-569
Spain
Madrid, Spain, 28040
Sweden
Göteborg, Sweden, 413 45
Sundsvall, Sweden, 851 86
Växjö, Sweden, 351 85
Switzerland
St. Gallen, Sankt Gallen, Switzerland, 9007
United Kingdom
Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00555919     History of Changes
Other Study ID Numbers: 91484, 2005-005581-36, 309821
Study First Received: November 8, 2007
Last Updated: October 9, 2014
Health Authority: Austria: Federal Office for Safety in Health Care
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ethics Committee
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Finland: Finnish Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Sweden: Medical Products Agency

Keywords provided by Bayer:
Metastatic breast cancer stage IV
Metastatic breast cancer
mBC
Stage IV breast cancer
Hormone receptor positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on November 25, 2014