Phase II Study of AZD2281 in Patients With Known BRCA Mutation Status or Recurrent High Grade Ovarian Cancer or Patients With Known BRCA Mutation Status/ Triple Neg Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00679783

Recruitment Status : Active, not recruiting

First Posted : May 19, 2008

Results First Posted : August 12, 2011

Last Update Posted : December 30, 2020

Sponsor:

Collaborator:

British Columbia Cancer Agency

Information provided by (Responsible Party):

AstraZeneca

Study Description

Brief Summary:

This is a Phase II, open label, non randomized correlative study of AZD2281 in patients with recurrent breast and ovarian cancer in both BRCA inherited mutation carriers and non-carriers to identify objective response rate and to assess for early markers of activity and to assess correlative markers that may provide helpful information for subsequent clinical trials. Approximately 110 patients from 7 centers in Canada will be enrolled into this study.

Condition or disease	Intervention/treatment	Phase
Ovarian Carcinoma Breast Cancer	Drug: AZD2281	Phase 2

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	99 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase II, Open Label, Non-Randomized Study of AZD2281 in the Treatment of Patients With Known BRCA or Recurrent High Grade Serous/ Undifferentiated Tubo-Ovarian Carcinoma and in Known BRCA or Triple Negative Breast Cancer to Determine Response Rate and Correlative Markers of Response
Actual Study Start Date :	July 8, 2008
Actual Primary Completion Date :	March 26, 2010
Estimated Study Completion Date :	December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Breast cancer Ovarian cancer

MedlinePlus related topics: Ovarian Cancer

Drug Information available for: Olaparib

Genetic and Rare Diseases Information Center resources: Ovarian Cancer Ovarian Epithelial Cancer

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 AZD2281, PARP inhibitor	Drug: AZD2281 PARP inhibitor Other Name: Olaparib

Outcome Measures

Primary Outcome Measures :

Objective Response Rate (ORR) Evaluated According to Response Evaluation Criteria In Solid Tumors (RECIST) Guidelines [ Time Frame: Each patient with measurable disease at baseline was assessed for Objective Response from the sequence of RECIST scan data up to data cut-off, 26 March 2010. RECIST scans were performed every 8 weeks (+/- 2 weeks) from randomization. ]
Percentage of participants with confirmed best RECIST response of complete response (CR) or partial response (PR). Patients with a best RECIST response of CR or PR had to have a confirmed response at least 28 days later.

Secondary Outcome Measures :

Disease Control Rate (DCR) [ Time Frame: 16 Weeks ]
Percentage of participants with confirmed best Response Evaluation Criteria In Solid Tumours (RECIST) response of complete response (CR), partial response (PR) orStable Disease (SD)
Duration of Response [ Time Frame: RECIST tumour assessments carried out every 8 weeks from randomization (+/- 2 weeks) until data cut-off on 26 March 2010. ]
Duration of response is measured from the time the measurement criteria for CR or PR are met (whichever is first recorded) until the patient progresses (per RECIST criteria). If patient did not progress, they are censored at their last objective tumour assessment date.
Best Percentage Change From Baseline in Tumour Size [ Time Frame: Each patient with measurable disease at baseline was assessed for best percentage change in tumour size from the sequence of RECIST scan data up to data cut-off, 26 March 2010. RECIST scans were performed every 8 weeks (+/- 2 weeks) from randomization. ]
The best percentage change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).
CA-125 Levels (Ovarian Cancer Patients Only) [ Time Frame: 24 weeks ]
A response according to CA-125 has occurred if there is at least a 50% reduction in CA-125 levels from a pre-treatment sample.
Progression Free Survival (PFS) [ Time Frame: RECIST tumour assessments carried out every 8 weeks from randomization (+/- 2 weeks) until data cut-off on 26 March 2010. ]
PFS is defined as the time from first dose to the earlier date of radiologic progression (as per Response Evaluation Criteria In Solid Tumours (RECIST) criteria or death by any cause in the absence of objective progression.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 130 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically confirmed high grade serous and/or undifferentiated carcinoma of ovary, fallopian tube or peritoneum
Oestrogen, progesterone and HER2 negative advanced adenocarcinoma of the breast
Known BRCA positive breast cancer or ovarian cancer, that is not high grade serous or undifferentiated tubo-ovarian carcinoma.
Performance status of no more than 2.

Exclusion Criteria:

Any chemotherapy, radiotherapy ( except palliative), endocrine or immunotherapy within 4 weeks prior to entry
Major surgery with 4 weeks of entering the study and must have recovered from effects of any major surgery .

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00679783

Locations

Layout table for location information

Canada, Alberta
Research Site
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Research Site
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Research Site
Hamilton, Ontario, Canada, L8V 5C2
Research Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H2X 3E4
Research Site
Montreal, Quebec, Canada, H3T 1E2

Sponsors and Collaborators

AstraZeneca

British Columbia Cancer Agency

Investigators

Layout table for investigator information

Study Chair:	Karen Gelmon, MD	British Columbia Cancer Agency
Study Director:	Jane Robertson, BSc, MBCHB, MD	AstraZeneca

More Information

Additional Information:

D0810C00020_CSR_Synopsis This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Matulonis UA, Penson RT, Domchek SM, Kaufman B, Shapira-Frommer R, Audeh MW, Kaye S, Molife LR, Gelmon KA, Robertson JD, Mann H, Ho TW, Coleman RL. Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Ann Oncol. 2016 Jun;27(6):1013-1019. doi: 10.1093/annonc/mdw133. Epub 2016 Mar 8.

Ang JE, Gourley C, Powell CB, High H, Shapira-Frommer R, Castonguay V, De Greve J, Atkinson T, Yap TA, Sandhu S, Banerjee S, Chen LM, Friedlander ML, Kaufman B, Oza AM, Matulonis U, Barber LJ, Kozarewa I, Fenwick K, Assiotis I, Campbell J, Chen L, de Bono JS, Gore ME, Lord CJ, Ashworth A, Kaye SB. Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin Cancer Res. 2013 Oct 1;19(19):5485-93. doi: 10.1158/1078-0432.CCR-13-1262. Epub 2013 Aug 6.

Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, Hirte H, Huntsman D, Clemons M, Gilks B, Yerushalmi R, Macpherson E, Carmichael J, Oza A. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011 Sep;12(9):852-61. doi: 10.1016/S1470-2045(11)70214-5. Epub 2011 Aug 19.

Layout table for additonal information

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00679783
Other Study ID Numbers:	D0810C00020
First Posted:	May 19, 2008 Key Record Dates
Results First Posted:	August 12, 2011
Last Update Posted:	December 30, 2020
Last Verified:	December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Supporting Materials:	Study Protocol Statistical Analysis Plan (SAP)
Time Frame:	AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria:	When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL:	https://astrazenecagroup-dt.pharmacm.com/DT/Home

Keywords provided by AstraZeneca:


Breast cancer Ovarian cancer BRCA Triple negative	Poly(ADP ribose) polymerases Known BRCA or Recurrent High Grade Serious/ Undifferentiated Tubo- Ovarian Carcinoma Known BRCA or Triple Negative Breast Cancer

Additional relevant MeSH terms:

Layout table for MeSH terms

Carcinoma Breast Neoplasms Ovarian Neoplasms Carcinoma, Ovarian Epithelial Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Endocrine Gland Neoplasms	Ovarian Diseases Adnexal Diseases Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders Olaparib Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents

To Top