Condition category
Cancer
Date applied
14/05/2015
Date assigned
14/05/2015
Last edited
20/10/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Miss Lynsey Houlton

ORCID ID

Contact details

The Institute of Cancer Research
ICR-CTSU
Division of Clinical Studies
15 Cotswold Road
Belmont
Sutton
SM2 5NG
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

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 measures

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

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes