Return to List

Study Summary
No. 2007-0098:.......Ovary......Karen H. Lu......Gynecologic Oncology
.
Study Summary Title
Study Summary
Number:
2007-0098
Study Title:A Phase II, open-label, non-comparative, international, multicenter study to assess the efficacy and safety of KU-0059436 given orally twice daily in patients with advanced BRCA1- or BRCA2-associated ovarian cancer
.
Physician New Patient Referral
Name:Karen H. LuPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Gynecologic OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-745-8902
Contact us about clinical trials
.
General Information
Disease Group:OvarySupported By:KuDOS Pharmaceuticals Limited (a member of the AstraZeneca group of companies), 327 Cambridge Science park, Milton Road, Cambridge, CB4 0WG, United Kingdom
Phase of Study:Phase IIReturn
Visit:
Weekly for three months, then monthly for a total of six months treatment.
There is a follow-up visit one month post treatment completion. Patients may
continue for longer than six months; visits will be monthly while they remain
on treatment.
Treatment
Agents:
KU-0059436Home Care:Medication (oral)
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
n/a
Description/
Intervention:
Unavailable
.
Study Objectives / Outcomes
PRIMARY:
  • To assess the efficacy of KU-0059436 in terms of objective tumour response rate when administered orally to patients with advanced BRCA1- or BRCA2-associated ovarian cancer.

SECONDARY:
  • To assess the efficacy of KU-0059436 at two dose levels in terms of clinical benefit rate (complete response [CR] and partial response [PD] and stable disease [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 profiles of KU-0059436 at two dose levels in peripheral blood mononuclear cells (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 (pharmacokinetic profile) to KU-0059436 at two dose levels following oral administration to patients with advanced BRCA1- or BRCA2-associated ovarian cancer.

EXPLORATORY:
  • To investigate exploratory biomarkers in serum, urine and tumour biopsies (on-study and historical), and their correlation with disease progression/response to therapy.
  • To investigate the pharmacodynamic profile of KU-0059436 in tumour tissue.
  • To obtain blood samples for deoxyribonucleic acid (DNA) extraction for future retrospective pharmacogenetic analysis of the activity of KU-0059436.
  • To conduct a preliminary assessment of Quality of Life (QoL) as measured by the European Profile of Quality of Life (EuroQOL) (EQ5D) and the Functional Assessment of Cancer Therapy – Ovarian Cancer (FACT-O) questionnaires.
.
Study Status Information
Study Activation / Registration Date:07/20/2007
IRB Review and Approval Date:06/05/2007
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Terminated
Projected Accrual:40
.
Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria: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 maetatases 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 positive.

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. Patients must have BRCA-1/2 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.

6) Estimated life expectancy (the participant's performance status) 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.

Exclusion Criteria:1) Patients who have had any treatment for their disease or high dose radiotherapy less than 28 days from active study therapy. 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 iducers of CYP3A4.

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 yars except for adequately treated stage I or II 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 treated with any antiepileptic 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).

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 [Clarification: Patients with abnormal bowel function (i.e. inability to tolerate oral medication without nausea or vomiting] 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 investigational medicinal product (IMP), or having participated in a study less than 28 days prior to the start of study treatment.

.
Links
Registration Number: NCT00494442
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
.
Results


Return to Clinical Trials at M.D. Anderson Cancer Center