Clinical trial NCT00679783: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: British Columbia Cancer Agency
First posted: 2008-05-19
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 4 parallel arms for the 2 tumour types and the BRCA mutation groups:

1. Triple negative breast Cancer with unknown BRCA mutation status: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally
2. Known BRCA mutation positive breast cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) to be administered orally
3. High grade serous/undifferentiated tubo-ovarian carcinoma with unknown BRCA status: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally
4. Known BRCA mutation positive ovarian cancer: AZD2281 400 mg bid (capsules)/ 300 mg bid (tablets) administered orally.
Primary purpose: TREATMENT

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


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 .

Primary outcomes:
measure: Objective Response Rate (ORR) Evaluated According to Response Evaluation Criteria In Solid Tumors (RECIST) Guidelines
timeFrame: 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 outcomes:
measure: Disease Control Rate (DCR)
timeFrame: 16 Weeks
measure: Duration of Response
timeFrame: RECIST tumour assessments carried out every 8 weeks from randomization (+/- 2 weeks) until data cut-off on 26 March 2010.
measure: Best Percentage Change From Baseline in Tumour Size
timeFrame: 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.
measure: CA-125 Levels (Ovarian Cancer Patients Only)
timeFrame: 24 weeks
measure: Progression Free Survival (PFS)
timeFrame: RECIST tumour assessments carried out every 8 weeks from randomization (+/- 2 weeks) until data cut-off on 26 March 2010.
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
Study officials:
affiliation: British Columbia Cancer Agency
name: Karen Gelmon, MD
role: STUDY_CHAIR
affiliation: AstraZeneca
name: Jane Robertson, BSc, MBCHB, MD
role: STUDY_DIRECTOR
References:
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.
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.
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.