Additional identifiers
EudraCT number
2014-003319-12
ClinicalTrials.gov number
Nil known
Protocol/serial number
18804
Study information
Scientific title
Window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO)
Acronym
RIO
Study hypothesis
The aim of the RIO trial is to determine the percentage of primary TNBCs or BRCA1/2 related breast cancers that display sensitivity to the PARP inhibitor rucaparib by measuring change in tumour cells multiplying after 12-14 days of rucaparib treatment. RIO will also aim to identify biomarkers that can identify patient groups sensitive to this medication to allow further analysis of rucaparib in these cancers.
Ethics approval
14/LO/2181; First MREC approval date 30/01/2015
Study design
Non-randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a participant information sheet
Condition
Topic: Cancer; Subtopic: Breast Cancer; Disease: Breast
Intervention
Rucaparib, All patients entering the trial will recieve rucaparib (600mg, twice daily) for 12-14 days. Following completion of rucaparib treatment patients will proceed to standard care.
Follow Up Length: 1 month(s); Study Entry : Registration only
Intervention type
Other
Phase
Phase II
Drug names
Primary outcome measure
Ki67 response from baseline to end of rucaparib in patients with sporadic triple negative cancers; Timepoint(s): Response to rucaparib is defined as 50% or greater fall in Ki67 from baseline.
Secondary outcome measures
N/A
Overall trial start date
18/06/2015
Overall trial end date
18/12/2016
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male or female patients aged 16 years or older
2. Histologically proven carcinoma of the breast amenable to biopsy
3. Either breast tumour size 2cm or greater OR <2cm tumour with cytologically or histologically confirmed axillary lymph node metastases
4. WHO performance status 0, 1 or 2
5. Either:
5.1. Primary sporadic triple negative breast cancer defined as oestrogen receptor (ER) negative, progesterone receptor (PgR) negative (as defined by Allred score 0/8 or 2/8 or stain in <1% of cancer cells) and HER2 negative (immunohistochemistry 0/1+ or negative in situ hybridization) as determined by local laboratory. Patients should not be known to have a germline pathogenic BRCA1 or BRCA2 mutation at study entry.
OR
5.2. Primary BRCA1/2 related breast cancer as defined by a breast carcinoma of any phenotype (ER +ve or –ve, PgR +ve or –ve, HER2 +ve or –ve) occurring in a patient with a known germline pathogenic BRCA1 or BRCA2 mutation
6. Adequate organ function confirmed by the following laboratory values obtained within 14 days prior to the first dose of rucaparib:
6.1. Bone marrow function: ANC ≥ 1.5 x 109/L; Platelets >100×109/L; Hemoglobin ≥9 g/dL
6.2. Hepatic function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN); Bilirubin ≤1.5 x ULN
6.3. Renal function: serum creatinine ≤1.5 x ULN
7. Patients or patients with partners of childbearing potential must use adequate contraception during trial participation. A negative pregnancy test is required by female patients prior to the of therapy. Female patients will be deemed not of childbearing potential if they are postmenopausal (aged >50 and amenorrhoeic for at least 12 months) or have had irreversible surgical sterilization
8. ER negative patients may enter the trial whether or not they have taken hormone replacement therapy (HRT) or the oral contraceptive pill (OCP) within the last four weeks. ER positive patients on HRT or the OCP must either continue HRT/OCP for the duration of the study or must not have taken HRT/OCP within the last four weeks before trial entry. The possible benefits and risks of continuing HRT/OCP must be discussed with the patient
9. Patients with primary breast cancer and evidence of metastatic disease on first presentation are eligible providing they have not had prior treatment
10. Patients must be willing and able to provide informed consent and to comply with all study procedures (including providing additional tumour biopsies for research purposes) and visit schedules
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 91; UK Sample Size: 91
Participant exclusion criteria
1. Any prior or concurrent treatment for the current diagnosis of breast cancer
2. Any anti-cancer treatment within the previous 12 months for prior diagnosis of cancer other than for basal cell carcinoma of the skin or cervical carcinoma in situ
3. Prior history of ipsilateral breast cancer within the previous 5 years
4. Impaired cardiac function or clinically significant cardiac disease, including any of the following:
4.1. Unstable angina pectoris =3 months prior to first scheduled dose of rucaparib
4.2. Acute myocardial infarction =3 months prior to first scheduled dose of rucaparib
5. Presence of any systemic illness incompatible with participation in the clinical trial or inability to provide written informed consent
6. Treatment with an unlicensed or investigational drug within 4 weeks prior to trial entry
7. Prior treatment with any PARP inhibitor, including oral or intravenous rucaparib
8. Administration of strong CYP1A2 and CYP3A4 inhibitors or inducers (as detailed in Appendix 1) =7 days prior to first scheduled dose of rucaparib
9. Females who are pregnant or breastfeeding
Recruitment start date
18/06/2015
Recruitment end date
18/12/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
The Institute of Cancer Research
ICR-CTSU
Division of Clinical Studies
15 Cotswold Road
Belmont
Sutton
SM2 5NG
United Kingdom
Sponsor information
Organisation
ICR Clinical Trials and Statistics Unit (ICR-CTSU)
Sponsor details
Institute of Cancer Research
Surrey Clinical Trials & Statistics Unit (ICR-CTSU)
Section of Clinical Trials Brookes
Lawley Building
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Clovis Oncology inc
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list