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Study Summary
No. 2008-0078:.......Fallopian Tube; Ovary; Peritoneum......Karen H. Lu......Gynecologic Oncology
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Study Summary Title
Study Summary
Number:
2008-0078
Study Title:A Phase II, Open-Label, Randomised, Comparative, International Multicentre Study to Compare the Safety and Efficacy of Two Different Doses of AZD2281 Given Orally Twice Daily versus Intravenous Liposomal Doxorubicin Given Monthly in Patients with Advanced BRCA-1or BRCA-2 Associated Ovarian Cancer Who Have Failed Previous Platinum-Based Chemotherapy
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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
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General Information
Disease Group:Fallopian Tube
Ovary
Peritoneum
Supported By:AstraZeneca
Phase of Study:Phase IIReturn
Visit:
Weekly
Treatment
Agents:
KU-0059436
Liposomal Doxorubicin
Home Care:oral medication, KU0059436 (AZD 2281)
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:
The goal of this clinical research study is to compare the effectiveness of 2
different dose levels of AZD2281 versus liposomal doxorubicin when given to
patients with BRCA-1 or BRCA-2 positive ovarian cancer. The safety of AZD2281
will also be studied.
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Study Objectives / Outcomes
Primary objective
To compare the efficacy of 3 different dose levels of AZD2281 with liposomal doxorubicin in patients with advanced BRCA1- or BRCA2-associated ovarian cancer. This will be assessed by the following:

primary variable
• progression-free survival (PFS)

secondary variables
• objective response rate [complete response (CR) and partial response (PR)] at various timepoints and overall
• overall duration of response
• tumor size
• CA-125 levels
• overall survival

Secondary objectives
The secondary objectives of the study are:
• To compare the safety and tolerability profile of two different dose levels of AZD2281 versus that of liposomal doxorubicin in the study population.
• To determine AZD2281 exposure at the 3 different dose levels following oral administration.
• To conduct a preliminary assessment of Quality of Life (QoL) as measured by the Functional Assessment of Cancer Therapy – Ovarian Cancer (FACT-O) questionnaire.

Exploratory objectives
• To obtain blood samples for deoxyribonucleic acid (DNA) extraction for future retrospective pharmacogenetic analysis of the activity of AZD2281.
• To obtain serum samples and historical tumor samples for future retrospective exploratory biomarker analysis and correlation with disease progression/response to therapy.
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Study Status Information
Study Activation / Registration Date:02/24/2009
IRB Review and Approval Date:08/11/2008
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Closed
Projected Accrual:90
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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 or older

2) Histologically or cytologically confirmed advanced ovarian cancer stage IIIB/IIIC/IV or recurrent ovarian cancer. 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 BRCA1 or BRCA2.

3) Confirmed BRCA1 or BRCA2 status (with a pre-existing genetic report & sequence scan). Please note: if there is a strong family history suggesting BRCA (+/-) status but it is unknown, then patients must not be randomized or receive study drug/comparator until a confirmatory genetic test report is received. 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 study drug/comparator.

5) ECOG performance status of 0-2.

6) Estimated life expectancy of at least 16 weeks.

7) Progressive or recurrent disease after platinum-based chemotherapy. (Note for patients with recurrence within 12 months of completion of most recent platinum chemotherapy, i.e., patients considered resistant or, at best, partially sensitive to platinum this recurrence does not need to be within 12 months of entering this study. The most recent treatment prior to study entry therefore need not comprise a platinum-based regime.

8) - continued from no. 7 - Cases where patients whose recurrence has occurrred greater than 12 months from completion of most recent platinum chemotherapy, may only be considered for this study if there is a codumented medical contraindication to further platinum chemotherapy and must be discussed and agreed with the Sponsor prior to consent).

9) Adequate bone marrow, hepatic and renal function, defined as: Haemoglobin >/=9.0 g/dL, White blood cells >3x10^9/L, Absolute neutrophil count >/=1.5x10^9/L, Platelets >/=100x10^9/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 </=5x ULN in the presence of liver metastases), Serum creatinine </=1.5 x ULN.

10) 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.

11) 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) 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 bisphosphonates if started prior to commencing study treatment and patients may receive palliative radiotherapy for bone disease during the study).

2) Prior treatment with liposomal doxorubicin.

3) Prior treatment with anthracyclines as a treatment for ovarian cancer. Patients who have received anthracyclines (non-liposomal doxorubicin or epirubicin) for the treatment of breast cancer are eligible provided the lifetime cumulative dose has not exceeded 240mg/m2 or 480 mg/m2 respectively at screening.

4) Patients requiring treatment with inhibitors or inducers of CYP3A4.

5) Patients with known brain metastases.

6) Any other malignancy which has been active or treated w/in d past 5 yrs, except adequately treated cone-biopsied in situ carcinoma of the cervix uteri & non-melanoma skin lesions or endometrial carcinoma stage 1A grade 1. Pts w/a history of breast cancer are not eligible if d disease was diagnosed w/in the past 5 yrs except for adequately treated stage I or II breast cancer w/out evidence of recurrent disease. Pts w/a history of breast cancer who received definitive treatment can participate even if they received adjuvant treatment during the 5 yrs prior to screening.

7) Persistent CTC grade 2 or greater toxicities (excluding alopecia) caused by prior therapy.

8) 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.

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

10) Left ventricular ejection fraction below 50%.

11) 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.

12) Presence of gastrointestinal disorders that, in the Investigator's opinion, are likely to interfere with the absorption of AZD2281 or with the patients ability to take regular oral medication.

13) Patients who are unable to swallow orally administered medication.

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

15) A positive pregnancy test. 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, practicing 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 & their partners must agree to use one of the above forms of contraception throughout the treatment period & for 3 months after end of treatment).

16) Simultaneous participation in any other study involving an investigational medicinal product, or having participated in a study less than 28 days prior to the start of study treatment.

17) Known hypersensitivity to any of the excipients in the AZD2281 or a conventional formulation of Doxorubicin HCl.

18) Previous treatment with AZD2281 or other drug with similar mode of action.

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Links
Registration Number: NCT00628251
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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