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. - ICEBERG

Phase 1

Conditions: Advanced breast cancer (stage IIIB/IIIC/IV) and confirmed BRCA+ status
MedDRA version: 9.1 Level: LLT Classification code 10006187 Term: Breast cancer

Registration Number: EUCTR2006-006458-91-GB

Lead Sponsor: KuDOS Pharmaceuticals Ltd. (a member of the AstraZeneca group of companies)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 54

Inclusion Criteria

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). This includes patients who develop metastatic disease at the time of relapse. 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. See Section 5.2.1 for further details. Patients must have BRCA1/2 mutations known to cause loss of gene function (clinical deleterious or suspected deleterious mutations).
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 (see Appendix 6).
6.Estimated life expectancy of at least 16 weeks.
7.Failed at least one prior chemotherapy and/or endocrine therapy in the advanced/metastatic setting, 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 > 3x109/L,
•Absolute neutrophil count = 1.5x109/L,
•Platelets = 100x109/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

1. Less than 28 days from active anti-cancer therapy such as chemotherapy, endocrine
therapy, antibody-based therapy (e.g. trastuzumab) 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 requiring treatment with inhibitors or inducers of CYP3A4 (see Section 3.5.1
for guidelines and wash-out periods).
3. Patients with brain metastases or central nervous system metastases that have any of the following features: 1) are progressive or have been symptomatic within 28 days of starting study treatment, 2) have not been resected or irradiated, 3) are the only site of measurable disease.
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. Patients with a history of ovarian cancer within the past 5 years are eligible in the case of adequately treated stage I or II ovarian cancer without any suspicion of recurrent disease such as peritoneal spread or increased CA-125 levels.
5. Persistent CTC grade 2 or greater toxicities (excluding alopecia) caused by prior
therapy.
6. Patients currently experiencing seizures or who are currently being treated with any
anti-epileptic for seizures (use of anti-epileptic drugs to control pain is allowed in
patients not suffering from seizures unless drug is excluded due to CYP3A4 induction -
phenytoin, carbamazepine, phenobarbitone, see Section 3.5.1).
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).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method