ZK 230211 in Postmenopausal Woman With Metastatic Breast Cancer

NCT00555919 | Completed Phase 2

• 3 other identifiers: 914842005-005581-36309821
• Study Type: interventional
• Target: 68
• Locations: 10 countries
• Sites: 28

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Keywords

Metastatic breast cancer stage IV; Metastatic breast cancer; mBC; Stage IV breast cancer; Hormone receptor positive breast cancer

Outcome Measures

Primary Outcomes (1)

• To evaluate efficacy (clinical benefit) of two doses of ZK PRA (25 mg and 100 mg) when administered once daily p.o.

  month 3, month 6

Secondary Outcomes (8)

• To evaluate safety and tolerability

  ongoing thoughout the trial

• To evaluate the pharmacokinetics of ZK PRA

  baseline, month1,2,6

• To evaluate the effect of ZK PRA on quality of life (QoL)

  baseline, month 1,2,3,4,5,6

• To perform exploratory analysis of biomarkers

  baseline, month 1, 3

• Progression-free survival (PFS)

  end of study

Study Arms (2)

Arm 1

EXPERIMENTAL

Drug: Lonaprisan (ZK 230211, BAY86-5044)

Arm 2

EXPERIMENTAL

Drug: Lonaprisan (ZK 230211, BAY86-5044)

Interventions

Lonaprisan (ZK 230211, BAY86-5044) DRUG

25 mg daily oral treatment

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (28)

Unknown Facility

Salzburg, Salzburg, 5020, Austria

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Vienna, Vienna, 1100, Austria

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Graz, 8036, Austria

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Innsbruck, 6020, Austria

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Turku, FIN-20521, Finland

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Vaasa, 65130, Finland

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Lille, 59020, France

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Lyon, 69008, France

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Montpellier, 34000, France

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Nantes, 44805, France

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Paris, 75020, France

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Reims, 51056, France

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Tübingen, Baden-Wurttemberg, 72076, Germany

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Erlangen, Bavaria, 91054, Germany

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Frankfurt am Main, Hesse, 60590, Germany

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Rostock, Mecklenburg-Vorpommern, 18059, Germany

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Kiel, Schleswig-Holstein, 24105, Germany

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Rozzano, Milano, 20089, Italy

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Bialystok, 15-540, Poland

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Gdansk, 80-219, Poland

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Olsztyn, 10-226, Poland

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Poznan, 60-569, Poland

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Madrid, Madrid, 28040, Spain

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Gothenburg, 413 45, Sweden

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Sundsvall, 851 86, Sweden

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Vaxjo, 351 85, Sweden

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Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

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Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

• Jonat W, Bachelot T, Ruhstaller T, Kuss I, Reimann U, Robertson JFR. Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer. Ann Oncol. 2013 Oct;24(10):2543-2548. doi: 10.1093/annonc/mdt216. Epub 2013 Jun 20.

  PMID: 23788750 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

lonaprisan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2007
• First Posted: November 9, 2007
• Study Start: March 1, 2008
• Primary Completion: April 1, 2010
• Study Completion: March 1, 2011
• Last Updated: October 10, 2014

Record last verified: 2014-10

Locations

ES (1); AU (4); SE (3); PL (4); CH (1); GB (1); DE (5); FR (6); FI (2); IT (1)