Advanced ovarian cancer (stage IIIB/IIIC/IV) and confirmed BRCA+ status MedDRA version: 9.1 Level: LLT Classification code 10033128 Term: Ovarian cancer
Conditions
Sponsors
KuDOS Pharmaceuticals Ltd. (a member of the AstraZeneca group of companies)
Eligibility
Sex/Gender
All
Inclusion criteria
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: 1. Female, aged 18 years or older. 2. Histologically or cytologically confirmed advanced ovarian cancer (stage IIIB/IIIC/IV). This includes patients who have developed recurrent ovarian cancer with macroscopic peritoneal metastases outside the pelvis or distant metastases. 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. In addition, patients with primary peritoneal carcinoma or Fallopian tube carcinoma may be considered for the study, as long as they are confirmed as being BRCA +ve. 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 in the advanced/metastatic setting and for whom, in the opinion of the Investigator, no curative standard therapy exists. 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
Exclusion criteria: To be eligible for inclusion into this study, the patient must not violate any of the following exclusion criteria within 28 days prior to Study Day 1, as defined in Section 5: 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 requiring treatment with inhibitors or inducers of CYP3A4 (see Section 3.5.1 for guidelines and wash-out periods). 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. Patients with a history of breast cancer are not eligible if the disease was diagnosed within the past 5 years except for adequately treated stage I or II breast cancer without evidence of recurrent disease. Patients with a history of breast cancer who received definitive treatment more than 5 years before screening can participate even if they received adjuvant treatment during the 5 years prior to screening. 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 post-menopausal, 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the efficacy of KU 0059436 at two dose levels in terms of objective tumour response rate when administered orally to patients with advanced BRCA1- or BRCA2-associated ovarian cancer.;Secondary Objective: • To assess the efficacy of KU-0059436 at two dose levels in terms of clinical benefit rate (complete response [CR] and PR and SD) at various timepoints and time to disease progression (TTP) when administered orally to patients with advanced BRCA1- or BRCA2 associated ovarian cancer. • To investigate the pharmacodynamic profile of two different dose levels KU 0059436 in PBMCs. • To assess the safety & tolerability profile of KU 0059436 at two dose levels when administered orally to patients with advanced BRCA1- or BRCA2-associated ovarian cancer. • To determine exposure to KU 0059436 at two dose levels following oral administration to patients with advanced BRCA1- or BRCA2-associated ovarian cancer. For exploratory objectives please refer to study protocol (protocol synopsis and overall design).;Primary end point(s): To assess the Objective Tumour Response Rate (proportion of patients with tumour response of CR + PR) of two dose levels of KU 0059436 after 4 cycles of treatment when administered orally to patients with advanced BRCA1- or BRCA2-associated ovarian cancer. | — |
Countries
Germany, Spain, Sweden, United Kingdom
Outcome results
None listed