Clinical trial NCT01078662: Open Label Study to Assess Efficacy and Safety of Olaparib in Confirmed Genetic BRCA1 or BRCA2 Mutation Pats
Official title: A Phase II, Open Label, Non Randomised, Non Comparative, Multicentre Study to Assess the Efficacy and Safety of Olaparib Given Orally Twice Daily in Patients With Advanced Cancers Who Have a Confirmed Genetic BRCA 1 and/or BRCA2 Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian
Breast
Prostate
Pancreatic
Advanced Tumours
Keywords: olaparib
PARP inhibitors
genetic BRCA1 mutation
BRCA2 mutation
solid tumour refractory
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-03-02
Enrollment: 298
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the efficacy of oral olaparib in patients with advanced cancer who have a confirmed genetic BRCA1 and/or BRCA2 mutation, by assessment of tumour response


Eligibility criteria: Inclusion Criteria:

* Confirmed documented deleterious or suspected deleterious BRCA mutation. (The presence of a loss-of-function germline mutation in the BRCA1 and/or BRCA2 gene must be confirmed prior to consent according to local practice).
* Confirmed malignant solid tumours for which no standard treatment exists
* At least one lesion (measurable and/or non measurable) at baseline that can be accurately assessed by CT/MRI and is suitable for repeated assessment at follow up visits

Exclusion Criteria:

* Any previous treatment with a PARP inhibitor, including olaparib
* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
* Patients receiving any systematic chemotherapy, radiotherapy (except for palliative reasons) within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used)

Primary outcomes:
measure: Tumour Response Rate
timeFrame: Tumour assessments carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Tumour assessments carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months
measure: Progression Free Survival
timeFrame: Tumour assessments are carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months
measure: Overall Survival
timeFrame: Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed maximum up to 29 months
measure: Overall Survival Rate at 12 Months
timeFrame: Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed maximum up to 29 months
measure: Duration of Response
timeFrame: From onset of first occurrence of complete or partial response till documented progression or death by any cause in the absence of progression, assessed maximum up to 29 months
measure: Disease Control Rate at Week 16
timeFrame: Tumour assessments carried out at baseline ie 28 days before first study drug dose and then at week 8 and week 16
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Research Site
city: Randwick
country: Australia
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Petah Tikva
country: Israel
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Jane Robertson, BSc, MBCHB, MD
role: STUDY_DIRECTOR
affiliation: Chaim Sheba Medical Centre, Tel Hashomer, Israel
name: Bella Kaufman, MD
role: PRINCIPAL_INVESTIGATOR
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: Domchek SM, Aghajanian C, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Loman N, Robertson JD, Mann H, Kaufman B. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol. 2016 Feb;140(2):199-203. doi: 10.1016/j.ygyno.2015.12.020. Epub 2015 Dec 23.