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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

Primary Purpose

Ovarian Carcinoma, Breast Cancer

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

AZD2281

About this trial

This is an interventional treatment trial for Ovarian Carcinoma focused on measuring 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

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 .

Sites / Locations

Research Site
Research Site
Research Site
Research Site
Research Site
Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Arm Description

Triple negative breast Cancer with unknown BRCA mutation status: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally AZD2281, PARP inhibitor Olaparib tablets, oral

Known BRCA mutation positive breast cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) to be administered orally AZD2281, PARP inhibitor Olaparib tablets, oral

High grade serous/undifferentiated tubo-ovarian carcinoma with unknown BRCA status: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally AZD2281, PARP inhibitor Olaparib tablets, oral

Known BRCA mutation positive ovarian cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally AZD2281, PARP inhibitor Olaparib tablets, oral

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR) Evaluated According to Response Evaluation Criteria In Solid Tumors (RECIST) Guidelines

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)

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

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

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)

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)

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.

Full Information

NCT ID

NCT00679783

First Posted

May 15, 2008

Last Updated

July 7, 2023

Sponsor

AstraZeneca

Collaborators

British Columbia Cancer Agency

1. Study Identification

Unique Protocol Identification Number

NCT00679783

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

July 8, 2008 (Actual)

Primary Completion Date

March 26, 2010 (Actual)

Study Completion Date

July 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

British Columbia Cancer Agency

4. Oversight

Data Monitoring Committee

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ovarian Carcinoma, Breast Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

4 parallel arms for the 2 tumour types and the BRCA mutation groups: Triple negative breast Cancer with unknown BRCA mutation status: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally Known BRCA mutation positive breast cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) to be administered orally High grade serous/undifferentiated tubo-ovarian carcinoma with unknown BRCA status: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally Known BRCA mutation positive ovarian cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

99 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Triple negative breast Cancer with unknown BRCA mutation status: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally AZD2281, PARP inhibitor Olaparib tablets, oral

Arm Title

Arm Type

Experimental

Arm Description

Known BRCA mutation positive breast cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) to be administered orally AZD2281, PARP inhibitor Olaparib tablets, oral

Arm Title

Arm Type

Experimental

Arm Description

Arm Title

Arm Type

Experimental

Arm Description

Known BRCA mutation positive ovarian cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally AZD2281, PARP inhibitor Olaparib tablets, oral

Intervention Type

Drug

Intervention Name(s)

AZD2281

Other Intervention Name(s)

Olaparib

Intervention Description

PARP inhibitor Olaparib tablets, oral

Primary Outcome Measure Information:

Title

Objective Response Rate (ORR) Evaluated According to Response Evaluation Criteria In Solid Tumors (RECIST) Guidelines

Description

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.

Secondary Outcome Measure Information:

Title

Disease Control Rate (DCR)

Description

Percentage of participants with confirmed best Response Evaluation Criteria In Solid Tumours (RECIST) response of complete response (CR), partial response (PR) orStable Disease (SD)

Time Frame

16 Weeks

Title

Duration of Response

Description

Time Frame

RECIST tumour assessments carried out every 8 weeks from randomization (+/- 2 weeks) until data cut-off on 26 March 2010.

Title

Best Percentage Change From Baseline in Tumour Size

Description

The best percentage change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).

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.

Title

CA-125 Levels (Ovarian Cancer Patients Only)

Description

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.

Time Frame

24 weeks

Title

Progression Free Survival (PFS)

Description

Time Frame

RECIST tumour assessments carried out every 8 weeks from randomization (+/- 2 weeks) until data cut-off on 26 March 2010.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

130 Years

Accepts Healthy Volunteers

Eligibility 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 .

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Karen Gelmon, MD

Organizational Affiliation

British Columbia Cancer Agency

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Jane Robertson, BSc, MBCHB, MD

Organizational Affiliation

AstraZeneca

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G 1Z2

Country

Canada

Facility Name

Research Site

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Z 4E6

Country

Canada

Facility Name

Research Site

City

Halifax

State/Province

Nova Scotia

ZIP/Postal Code

B3H 1V7

Country

Canada

Facility Name

Research Site

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8V 5C2

Country

Canada

Facility Name

Research Site

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4N 3M5

Country

Canada

Facility Name

Research Site

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H2X 3E4

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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

IPD Sharing 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

IPD Sharing 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

IPD Sharing URL

https://astrazenecagroup-dt.pharmacm.com/DT/Home

Citations:

PubMed Identifier

26961146

Citation

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.

Results Reference

derived

PubMed Identifier

23922302

Citation

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.

Results Reference

derived

PubMed Identifier

21862407

Citation

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.

Results Reference

derived

Links:

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=194&filename=D0810C00020.pdf

Description

D0810C00020_CSR_Synopsis

Learn more about this trial

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

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