ZK 230211 in Postmenopausal Woman With Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00555919
• Other study ID #: 91484
• Secondary ID: 2005-005581-3630
• Status: Completed
• Phase: Phase 2
• First received: November 8, 2007
• Last updated: October 9, 2014
• Start date: March 2008
• Est. completion date: March 2011

Study information

• Verified date: October 2014
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareGermany: Federal Institute for Drugs and Medical DevicesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: Ethics CommitteeSpain: Spanish Agency of MedicinesSwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyFinland: Finnish Medicines AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: March 2011
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Lonaprisan (ZK 230211, BAY86-5044)
25 mg daily oral treatment
• Lonaprisan (ZK 230211, BAY86-5044)
100 mg daily oral treatment

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Austria,  Finland,  France,  Germany,  Italy,  Poland,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (1)

Jonat W, Bachelot T, Ruhstaller T, Kuss I, Reimann U, Robertson JF. Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer. Ann Oncol. 2013 Oct;24(10):2543-8. doi: 10.1093/annonc/mdt216. Epub 2013 Jun 20. — View Citation

Outcome

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

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