A phase II, open-label, non-comparative, international, multicentre study to assess the efficacy and safety of KU 0059436 given orally twice daily in patients with advanced BRCA1- or BRCA2-associated breast cancer.Estudio de fase II, abierto, no comparativo, internacional y multicéntrico, para evaluar la eficacia y la seguridad de KU-0059436 administrado dos veces al día por vía oral en pacientes con cáncer de mama avanzado asociado a BRCA1 o BRCA2 - ICEBERG

• Conditions: Advanced breast cancer (stage IIIB/IIIC/IV) and confirmed BRCA+ statusCáncer de mama avanzado (estadíos IIIB/IIIC/IV) y con estado BRCA+ confirmado; MedDRA version: 9.1Level: LLTClassification code 10006187Term: Breast cancer

• Registration Number: EUCTR2006-006458-91-ES
• Lead Sponsor: KuDOS Pharmaceuticals Ltd. (a member of the AstraZeneca group of companies)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-04-18
• Last Update Posted: 7 August 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 40

Inclusion Criteria

To be eligible for inclusion into this study, each patient must fulfil the following inclusion criteria within 28 days prior to Study Day 1, as defined in Section 5 of the protocol:

1.Female, aged 18 years or older.

2.Histologically or cytologically confirmed breast cancer that is locally advanced (not amenable to curative surgery and/or radiation) or has metastasised (Stage IIIB/IIIC or IV, respectively, according to the American Joint Committee on Cancer Criteria). Patients with spinal cord compression may be considered if they have received definitive treatment for this and evidence of clinically stable disease for at least 28 days.

3.Confirmed BRCA1 or BRCA2 status (with a pre-existing genetic report & sequence scan). Please note: if there is a strong family history and evidence suggesting BRCA-/- status, then patients may be screened for the study, but must not receive IMP until a confirmatory Myriad Genetics sequence report is received.

4.One or more measurable lesions, at least 10 mm in the longest diameter (LD) by spiral CT scan, or 20 mm with conventional techniques, according to RECIST criteria, not irradiated within 12 weeks of the first administration of IMP.

5.ECOG performance status of 0 – 2.

6.Estimated life expectancy of at least 16 weeks.

7.Failed at least one prior chemotherapy and/or endocrine therapy, and for whom, in the opinion of the Investigator, no curative standard therapy exists. Patients whose tumours are histologically Estrogen Receptor positive (ER+) and/or Progesterone Receptor positive (PR+) must have had at least one line of hormonal therapy, for which there will have to be a washout period of at least 28 days prior to trial entry.

8.Adequate bone marrow, hepatic and renal function, defined as:
•Haemoglobin >= 9.0 g/dL,
•White blood cells > 3x10e9/L,
•Absolute neutrophil count >= 1.5x10e9/L,
•Platelets >=100x10e9/L,
•Total bilirubin <= 1.5 x upper limit of normal (ULN),
•Aspartate transaminase (AST) (SGOT) and alanine transaminase (ALT) (SGPT) <= 2.5 x ULN (or = 5 x ULN in the presence of liver metastases),
•Serum creatinine <= 1.5 x ULN.

9.The patient is willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations.

10.The patient has given written informed consent prior to any study-related procedure not constituting part of the standard care for the condition, with the understanding that said consent may be withdrawn at any time, without prejudice to any future medical care.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

To be eligible for inclusion into this study, each patient must violate none of the following exclusion criteria within 28 days prior to Study Day 1, as defined in Section 5 of the protocl:

1.Less than 28 days from active therapy (i.e. any treatment used to treat the disease) or high dose radiotherapy (patients may continue concomitant use of bisphosphonates if used for at least 28 days prior to commencing study treatment and patients may receive palliative radiotherapy for bone disease during the study).

2.Patients who have been previously treated with inhibitors or inducers of the cytochrome P450 isozyme family, must have completed treatment at least 4 weeks prior to the first administration of IMP (unless otherwise stated as less in Section 3.5.1 of the protocol). In the case of fluoxetine and phenobarbitone, 5 weeks must have elapsed prior to the first administration of IMP.

3.Patients with brain metastases.

4.Any other malignancy which has been active or treated within the past 5 years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions.

5.Persistent grade 2 or greater toxicities (excluding alopecia) from any cause.

6.Patients currently experiencing seizures or who are currently treated with any anti-epileptic.

7.Major thoracic and/or abdominal surgery in the four weeks prior to the start of study treatment.

8.Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.

9.Presence of gastrointestinal disorders that, in the Investigator’s opinion, are likely to interfere with the absorption of the IMP.

10.Patients who are unable to swallow orally administered medication.

11.Patients who are immunocompromised, e.g. patients known to be serologically positive for human immunodeficiency virus (HIV).

12.Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used (lack of childbearing potential is met by being postmenopausal, being surgically sterile, practising contraception with an oral contraceptive or other hormonal therapy [e.g. hormone implants], intra-uterine device, diaphragm with spermicide or condom with spermicide, or being sexually inactive. Patients and their partners must agree to use one of the above forms of contraception throughout the treatment period and for 3 months after discontinuation of treatment).

13.Simultaneous participation in any other study involving an IMP, or having participated in a study less than 28 days prior to the start of study treatment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified