Clinical trial NCT00555919: ZK 230211 in Postmenopausal Woman With Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: Metastatic breast cancer stage IV
Metastatic breast cancer
mBC
Stage IV breast cancer
Hormone receptor positive breast cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2007-11-09
Enrollment: 68
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: To evaluate efficacy (clinical benefit) of two doses of ZK PRA (25 mg and 100 mg) when administered once daily p.o.
timeFrame: month 3, month 6
Secondary outcomes:
measure: To evaluate safety and tolerability
timeFrame: ongoing thoughout the trial
measure: To evaluate the pharmacokinetics of ZK PRA
timeFrame: baseline, month1,2,6
measure: To evaluate the effect of ZK PRA on quality of life (QoL)
timeFrame: baseline, month 1,2,3,4,5,6
measure: To perform exploratory analysis of biomarkers
timeFrame: baseline, month 1, 3
measure: Progression-free survival (PFS)
timeFrame: end of study
measure: Objective response rate (ORR) / Duration of response - in the subset of patients with measurable disease
timeFrame: end of study
measure: Duration of Clinical Benefit
timeFrame: end of study
measure: Overall Survival (OS)
timeFrame: end of study
Other outcomes:
Locations:
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Salzburg
country: Austria
city: Wien
country: Austria
city: Turku
country: Finland
city: Vaasa
country: Finland
city: Lille
country: France
city: Lyon Cedex
country: France
city: Montpellier
country: France
city: Nantes
country: France
city: Paris
country: France
city: Reims
country: France
city: Tübingen
country: Germany
state: Baden-Württemberg
city: Erlangen
country: Germany
state: Bayern
city: Frankfurt
country: Germany
state: Hessen
city: Rostock
country: Germany
state: Mecklenburg-Vorpommern
city: Kiel
country: Germany
state: Schleswig-Holstein
city: Rozzano
country: Italy
state: Milano
city: Bialystok
country: Poland
city: Gdansk
country: Poland
city: Olsztyn
country: Poland
city: Poznan
country: Poland
city: Madrid
country: Spain
city: Göteborg
country: Sweden
city: Sundsvall
country: Sweden
city: Växjö
country: Sweden
city: St. Gallen
country: Switzerland
state: Sankt Gallen
city: Nottingham
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.