Condition category
Cancer
Date applied
04/12/2017
Date assigned
19/01/2018
Last edited
14/05/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Ms Naomi McGregor

ORCID ID

Contact details

Oncology Clinical Trials Office (OCTO)
Department of Oncology
University of Oxford
Old Road Campus Research Building
Roosevelt Drive
Oxford
OX3 7DQ
United Kingdom
+44 1865 227196
octo-octova@oncology.ox.ac.uk

Additional identifiers

EudraCT number

2016-000559-28

ClinicalTrials.gov number

Protocol/serial number

32967

Study information

Scientific title

Randomised phase II Trial of olaparib, chemotherapy or olaparib and cediranib in patients with BRCA mutated platinum–resistant ovarian cancer

Acronym

OCTOVA

Study hypothesis

Study aim:
The aim of this study is to comparing efficacy and tolerability of single agent olaparib with:
1. Weekly paclitaxel
2. The combination of olaparib and cediranib

Hypthosis:
Olaparib will provide similar outcomes but less toxicity than paclitaxel and that olaparib/cediranib combination might provide better outcomes.

Ethics approval

London – Chelsea Research Ethics Committee, 25/01/2017, ref: 16/LO/2150

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Specialty: Cancer, Primary sub-specialty: Gynaecological Cancers; UKCRC code/ Disease: Cancer/ Malignant neoplasms of female genital organs

Intervention

This study is a 3-arm randomised trial. PArticipants are randomly allocated to one of the following groups:
Arm A: Participants receive weekly paclitaxel (repeating cycles days 1, 8 and 15 of 28)
Arm B: Participants receive twice-daily olaparib tablets
Arm C: Participants receive twice-daily olaparib and daily cediranib tablets

In all cases treatment continues until disease progression (RECIST). In Arm A only, after progression patients can then switch to treatment with olaparib – this, like Arm B treatment, can continue until further progression.

Recruitment target is 132 patients, 44 per arm. Stratification factors are previous PARP and previous antiangiogenic therapy.

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measure

Progression free survival is measured using RECIST V1.1 criteria at 8-weekly.

Secondary outcome measures

1. Overall survival is measured at 12 and 18 months
2. Objective response rate is measured using RECIST V1.1 and GCIG CA125 criteria at 8-weekly
3. Quality of life measured using EQ5D, EORTC-QLQ C30 and OV28 questionnaire at 4-weekly - baseline, Cycles 2+ day 1, End of Treatment visit
4. Safety and tolerability of the combination of olaparib and cediranib is measured using Adverse Events using CTCAE v4.03 at weekly during Cycle 1, 2-weekly during Cycles 2 and 3, monthly form Cycle 4 onward

Overall trial start date

02/03/2015

Overall trial end date

30/06/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Female patients, age 16 years and older with relapsed BRCA (germline or somatic) mutated epithelial ovarian, primary peritoneal or fallopian tube cancer who have relapsed in a platinum resistant time frame, i.e. have progressed within 6 months of previous platinum-based therapy. Their most recent chemotherapy does not have to have been platinum-based.
2. Patients can have received prior PARP inhibitor and antiangiogenic therapy, but there must be a > 6 month interval since treatment
3. Measurable disease by RECIST Version 1.1 performed in past 4 weeks. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
4. Sufficient archival tissue confirming histological diagnosis available
5. ECOG PS 0-2
6. Able to swallow and retain oral medications
7. Life expectancy > 12 weeks in terms of disease related mortality
8. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
9. Written (signed and dated) informed consent prior to any study specific procedures and be capable of co-operating with protocol
10. Patients must have:
10.1. Haemoglobin ≥ 10.0 g/dL and no blood transfusions in the 28 days prior to randomisation
11. Patients must have normal organ and bone marrow function measured within 14 days prior to administration of study treatment as defined below:
11.1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
11.1.1. No features suggestive of MDS/AML on peripheral blood smear
11.2. White blood cells (WBC) > 3x109/L
11.3. Platelet count > 100 x 109/L
11.4. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
11.5. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
11.6. Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) or calculated creatinine clearance >50 ml/min calculated using Cockroft-Gault, Jelliffe or Wright (see Appendix 4)
11.7. Urine dipstick for proteinuria <2+. If urine dipstick is ≥ 2+ on two occasions more than one week apart then a 24-hour urine must demonstrate ≤ 1 g of protein in 24 hours or protein/creatinine ratio < 1.5

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 132; UK Sample Size: 132

Participant exclusion criteria

1. Received previous single agent weekly paclitaxel for relapsed disease
2. Pregnant or breast-feeding women or women of childbearing potential unless effective methods of contraception are used during the trial and for 6 months after stopping treatment. Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1. Pregnancy test will be performed monthly in women of child bearing potential.
Postmenopausal is defined as: Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments, LH and FSH levels in the post-menopausal range for women under 50, radiation-induced oophorectomy with last menses >1 year ago, chemotherapy-induced menopause with >1 year interval since last menses, or surgical sterilisation (bilateral oophorectomy or hysterectomy).
3. Treatment with any other investigational agent, systemic chemotherapy, or participation in another interventional clinical trial within 28 days prior to enrolment
4. Radiotherapy within 2 weeks from the last dose prior to study treatment
5. Started a stable dose of bisphosphonates for bone metastases less than 4 weeks prior to treatment with study drug e.g. patient is eligible and can continue to take bisphosphonates if these were started at least 4 weeks prior to treatment with study drug
6. Concomitant use of known CYP3A4 inhibitors such as ketokonazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir
7. Concomitant use of potent inducers of CYP3A4 such as rifampicin, carbamazepine, phenobarbital, phenytoin and St. John Wort
8. Persistent toxicities (>=CTCAE grade 2), with the exception of alopecia, caused by previous cancer therapy
9. Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
10. Blood transfusions within 1 month prior to study start
11. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
12. Patients with symptomatic, untreated, uncontrolled brain or meningeal metastases or tumour
12.1. A scan to confirm the absence of brain metastases is not require
12.2. Patients with radiological evidence of stable brain metastases are eligible, providing that they are asymptomatic and:
12.2.1. Do not require corticosteroids, or
12.2.2. Have previously been treated with corticosteroids, with clinical and radiological evidence of stabilisation at least 10 days after discontinuation of steroids
12.2.3. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment.
13. Major surgery within 14 days of starting study treatment
14. Patients who have not recovered from any effects of any major surgery.
15. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on HRCT scan
16. Any psychiatric disorder that prohibits obtaining informed consent.
17. Left Ventricular Ejection Fraction (LVEF) < institutional lower limit of normal, when:
17.1. Prior treatment with anthracyclines
17.2. Prior treatment with trastuzumab
17.3. A NYHA classification of II controlled with treatment (see Appendix 2)
17.4. Prior central thoracic RT, including RT to the heart
17.5. History of myocardial infarction within the prior 12 months
18. Poorly controlled hypertension (persistently elevated > 150/100mmHg, either systolic or diastolic or both, despite anti-hypertensive medication)
19. History of inflammatory bowel disease
20. History of cerebrovascular accident (including transient ischaemic attacks) within last 12 months.
21. Gastro intestinal impairment that could affect ability to take, or absorption of, oral medicines including sub- acute or complete bowel obstruction
22. Evidence of severe or uncontrolled cardiac disease
23. Evidence of active bleeding or bleeding diathesis. Defined as significant haemorrhage (>30mL bleeding/episode in previous 3 months) or haemoptysis (>5mL fresh blood in previous 4 weeks).
24. Known treatment limiting hypersensitivity to cediranib, olaparib, paclitaxel or any of its excipients
25. Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results
26. Any other active malignancy, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions, requiring treatment/or whose prognosis will prevent readout from trial endpoints
27. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV
28. Immunocompromised patients e.g., patients who are taking immunosuppressive drugs

Recruitment start date

09/03/2017

Recruitment end date

30/09/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Trial participating centre

Christie Hospital
Wilmslow Road
Manchester
M20 4BX
United Kingdom

Trial participating centre

Churchill Hospital
Old Road Headington
Oxford
OX3 7LE
United Kingdom

Trial participating centre

Clatterbridge Cancer Centre
Clatterbridge Road Birkenhead
Wirral
CH63 4JY
United Kingdom

Trial participating centre

Mount Vernon Cancer Centre
Rickmansworth Road
Northwood
HA6 2RN
United Kingdom

Trial participating centre

Royal Marsden Hospital Chelsea
203 Fulham Road Chelsea
London,
SW3 6JJ
United Kingdom

Trial participating centre

Royal Marsden Hospital Sutton
Downs Road
Sutton
SM2 5PT
United Kingdom

Trial participating centre

Royal United Hospital
Combe Park Avon
Bath
BA1 3NG
United Kingdom

Trial participating centre

University College London Hospital
Cancer Institute Huntley Street
London
WC1E 6AG
United Kingdom

Trial participating centre

Velindre Cancer Centre
Velindre Road
Cardiff
CF14 2TL
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Clinical Trials and Research Governance
Oxford
OX1 2JD
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

AstraZeneca UK Limited

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

01/06/2022

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

14/05/2018: Cancer Research UK lay summary link added to plain English summary field 23/01/2018: The registration of this study was requested through the NIHR Portfolio. The trialist confirmed the recruitment start and end dates.