Trial of different drug and treatment combinations for patients who are considering further therapy to treat their ovarian cancer
| ISRCTN | ISRCTN14784018 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14784018 |
| EudraCT/CTIS number | 2016-000559-28 |
| ClinicalTrials.gov number | NCT03117933 |
| Secondary identifying numbers | CPMS 32967 |
- Submission date
- 04/12/2017
- Registration date
- 19/01/2018
- Last edited
- 20/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Contact information
Ms Naomi McGregor
Public
Public
Oncology Clinical Trials Office (OCTO)
Department of Oncology
University of Oxford
Old Road Campus Research Building
Roosevelt Drive
Oxford
OX3 7DQ
United Kingdom
| Phone | +44 1865 227196 |
|---|---|
| octo-octova@oncology.ox.ac.uk |
Study information
| Study design | Randomized; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | ISRCTN14784018_PIS_V4.0_04Jul17.pdf |
| Scientific title | Randomised phase II Trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer |
| Study 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 Hypothesis: Olaparib will provide similar outcomes but less toxicity than paclitaxel and that olaparib/cediranib combination might provide better outcomes. |
| Ethics approval(s) | London – Chelsea Research Ethics Committee, 25/01/2017, ref: 16/LO/2150 |
| Condition | Ovarian cancer |
| Intervention | Current interventions as of 21/11/2019: This study is a three-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 138 patients, 46 per arm. Stratification factors are previous PARP, previous antiangiogenic therapy, and BRCA mutation. _____ Previous interventions: This study is a three-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 |
| 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 study start date | 02/03/2015 |
| Overall study end date | 30/06/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 138; UK Sample Size: 138 |
| Total final enrolment | 139 |
| Participant inclusion criteria | Current inclusion criteria as of 21/11/2019: 1. Female patients, age 16 years and older with epithelial ovarian, primary peritoneal or fallopian tube cancer who have relapsed within 12 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 but there must be a > 6 month interval since treatment 3. Patients can have received prior anti-angiogenic therapy, but there must be a > 6 month interval since treatment; except for bevacizumab where a 6 week interval is required 4. 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. 5. Sufficient archival tissue confirming histological diagnosis available 6. ECOG PS 0-2 7. Able to swallow and retain oral medications 8. 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 10. Written (signed and dated) informed consent prior to any study specific procedures and be capable of co-operating with protocol 11. Patients must have haemoglobin ≥ 9.0 g/dL and no blood transfusions in the 28 days prior to randomisation 12. Patients must have normal organ and bone marrow function measured within 14 days prior to administration of study treatment as defined below: 12.1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L 12.2. Platelet count > 100 x 109/L 12.3. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) 12.4. 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 12.5. 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) 12.6. 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 _____ Previous 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 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 | 10/01/2020 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
Glasgow
G12 0YN
United Kingdom
Christie Hospital
Wilmslow Road
Manchester
M20 4BX
United Kingdom
Manchester
M20 4BX
United Kingdom
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
Headington
Oxford
OX3 7LE
United Kingdom
Clatterbridge Cancer Centre
Clatterbridge Road
Birkenhead
Wirral
CH63 4JY
United Kingdom
Birkenhead
Wirral
CH63 4JY
United Kingdom
Mount Vernon Cancer Centre
Rickmansworth Road
Northwood
HA6 2RN
United Kingdom
Northwood
HA6 2RN
United Kingdom
Royal Marsden Hospital Chelsea
203 Fulham Road
Chelsea
London
SW3 6JJ
United Kingdom
Chelsea
London
SW3 6JJ
United Kingdom
Royal Marsden Hospital Sutton
Downs Road
Sutton
SM2 5PT
United Kingdom
Sutton
SM2 5PT
United Kingdom
Royal United Hospital
Combe Park
Avon
Bath
BA1 3NG
United Kingdom
Avon
Bath
BA1 3NG
United Kingdom
University College London Hospital
Cancer Institute
Huntley Street
London
WC1E 6AG
United Kingdom
Huntley Street
London
WC1E 6AG
United Kingdom
Velindre Cancer Centre
Velindre Road
Cardiff
CF14 2TL
United Kingdom
Cardiff
CF14 2TL
United Kingdom
Hammersmith Hospital
72 Du Cane Rd
Shepherd's Bush
London
W12 0HS
United Kingdom
Shepherd's Bush
London
W12 0HS
United Kingdom
St Bartholomew’s Hospital
West Smithfield
London
EC1A 7BE
United Kingdom
London
EC1A 7BE
United Kingdom
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Belfast City Hospital
51 Lisburn Road
Belfast
BT9 7AB
United Kingdom
Belfast
BT9 7AB
United Kingdom
Royal Surrey County Hospital
Egerton Road
Guildford
GU2 7XX
United Kingdom
Guildford
GU2 7XX
United Kingdom
Sponsor information
University of Oxford
Hospital/treatment centre
Hospital/treatment centre
Clinical Trials and Research Governance
Oxford
OX1 2JD
England
United Kingdom
"ROR" |
https://ror.org/052gg0110 |
|---|
Funders
Funder type
Industry
AstraZeneca UK Limited
No information available
Results and Publications
| Intention to publish date | 31/12/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version V4.0 | 04/07/2017 | 19/01/2018 | No | Yes |
| Protocol article | protocol | 15/01/2021 | 18/01/2021 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 20/01/2024 | 22/01/2024 | Yes | No | |
| Plain English results | 20/12/2024 | No | Yes |
Additional files
- ISRCTN14784018_PIS_V4.0_04Jul17.pdf
- Uploaded 19/01/2018
Editorial Notes
20/12/2024: Cancer Research UK plain English results link added.
22/01/2024: Publication reference added.
08/06/2023: The intention to publish date was changed from 01/06/2023 to 31/12/2023.
07/12/2022: The intention to publish date was changed from 01/06/2022 to 01/06/2023.
18/01/2021: Publication reference added.
10/02/2020: The total final enrolment number has been added.
29/01/2020: The recruitment end date has been changed from 31/12/2019 to 10/01/2020.
10/01/2020: ClinicalTrials.gov number added.
21/11/2019: The following changes were made to the trial record:
1. The public title was changed from "Trial of different drug and treatment combinations for patients with inherited genetic changes who are considering further therapy to treat their ovarian cancer" to "Trial of different drug and treatment combinations for patients who are considering further therapy to treat their ovarian cancer".
2. The scientific title was changed from "Randomised phase II Trial of olaparib, chemotherapy or olaparib and cediranib in patients with BRCA mutated platinum–resistant ovarian cancer" to "Randomised phase II Trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum–resistant ovarian cancer".
3. The inclusion criteria were changed.
4. The target number of participants was changed from "Planned Sample Size: 132; UK Sample Size: 132" to "Planned Sample Size: 138; UK Sample Size: 138".
5. The trial participating centres were added: Hammersmith Hospital, St Bartholomew’s Hospital, Nottingham City Hospital, Belfast City Hospital, Royal Surrey County Hospital.
20/11/2019: The recruitment end date was changed from 30/09/2019 to 31/12/2019.
27/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Gynaecological Cancers; UKCRC code/ Disease: Cancer/ Malignant neoplasms of female genital organs" to "Ovarian cancer" following a request from the NIHR.
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.
