OCTOPUS - ovarian cancer trials of weekly paclitaxel

ISRCTN	ISRCTN16426935
DOI	https://doi.org/10.1186/ISRCTN16426935
EudraCT/CTIS number	2014-005221-12
Secondary identifying numbers	OCTOPUS-2014

Submission date: 20/10/2015
Registration date: 21/10/2015
Last edited: 20/03/2023

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 of protocol

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-azd2014-and-paclitaxel-for-women-with-ovarian-cancer-that-has-come-back-octopus

Study website

Contact information

Ms Liz-Anne Lewsley
Public

Cancer Research UK Clinical Trials Unit
The Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Study information

Study design	Randomised, placebo-controlled, double blind multi centre trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet
Scientific title	A randomised phase II umbrella trial of weekly paclitaxel +/- novel agents in platinum-resistant ovarian cancer
Study acronym	OCTOPUS
Study objectives	Addition of novel agents to weekly paclitaxel will improve clinical efficacy compared to paclitaxel alone in patients with platinum-resistant/refractory, high grade serous ovarian (fallopian tube, primary peritoneal) carcinoma.
Ethics approval(s)	Brighton and Sussex NRES Committee, 09/10/2015, ref:15/LO/1302
Health condition(s) or problem(s) studied	Ovarian cancer
Intervention	1. Control arm: Paclitaxel 80mg/m2 IV D1, 8, 15 of a 28 day cycle (3 weeks on, 1 week off) + placebo 2. Experimental arm: Paclitaxel 80mg/m2 IV D1, 8, 15 of a 28 day cycle (3 weeks on, 1 week off) + AZD2014 Patients who need to stop weekly paclitaxel prior to completing four cycles will require to come off study drug, but continue to be followed up as per protocol (i.e. cannot continue on continuous novel study drug/placebo). Patients going beyond 6 cycles can continue with weekly paclitaxel at the discretion of the Investigator however confirmation is required by the chief investigator.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Paclitaxel, vistusertib (AZD2014)
Primary outcome measure	Progression-free survival (PFS) based on combined RECIST v1.1/GCIG CA125 criteria is measured using Radiological/CA125 Disease Assessment every 8 weeks for the 1st year and then every 12 weeks therefore (or until evidence of progression).
Secondary outcome measures	1. Response (based on RECIST 1.1 and GCIG CA125 criteria) is measured using Radiological/CA125 Disease Assessment every 8 weeks for the 1st year and then every 12 weeks therefore (or until evidence of progression) 2. Overall survival is measured documenting patient status every 8 weeks for the first year and every 12 weeks thereafter 3. Safety and tolerability are measured using Blood parameters, toxicity assessment every 4 weeks during treatment 4. Quality of life (QoL) is measured using EQ-5D assessment every 4 weeks while on treatment then every 8 weeks in the 1st year following completion of treatment and then every 12 weeks (or until evidence of progression) 5. Resource use for health economic assessment is measured using EQ-5D assessment every 4 weeks while on treatment then every 8 weeks in the 1st year following completion of treatment and then every 12 weeks (or until evidence of progression)
Overall study start date	30/10/2015
Completion date	08/12/2019

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target number of participants	140
Key inclusion criteria	1. Age ≥ 18 years 2. Histologically confirmed high grade serous ovarian, fallopian tube or primary peritoneal cancer (please note that patients who have an original diagnosis based on cytology only will not be eligible for entry into the study unless a biopsy confirming high grade serous histology is performed). Please note that Grade 3 serous on pathology reports are accepted as high grade serous. Any patient originally diagnosed with a ‘grade 2 serous’ pathology must undergo pathology review to confirm high grade pathology 3. Platinum-resistant disease defined as progression within 6 months of completing prior platinum therapy. This includes platinum-refractory disease. Progression is defined by RECIST criteria v1.1 (radiologically with measurable disease), but patients with CA125 progression (GCIG CA125 Criteria (see Appendix 3 for full definition)) plus symptoms indicative of progression will also be allowed to enter. 4. Measurable or evaluable disease (if not measurable by RECIST criteria v1.1, must be evaluable by GCIG CA125 criteria – see Appendix 3 for full definition). Patients with CA125 progression in the absence of symptoms will NOT be eligible 5. Histological tissue specimen available (tissue block or 8-10 unstained slides) must be available (specimen can be the sample at diagnosis or taken at relapse). Otherwise, a biopsy must be carried out to obtain sufficient tissue for histological assessment 6. Willingness to undergo mandatory biopsy pre cycle 1 day 1. Target lesions (RECIST criteria v1.1) should be avoided if possible 7. Prior taxane use: Patients whom have received prior 3 weekly paclitaxel (or other 3 weekly taxane) are permitted. Patients whom received weekly paclitaxel as part of first line treatment in combination with platinum are eligible if the interval since the last dose of weekly paclitaxel is > 6months at the time of randomisation. Patients whom received prior weekly paclitaxel (alone or in combination) for platinum-resistant disease are excluded. If patients have received prior taxane, the interval since the last taxane treatment must be known. The treatment immediately prior to study entry need not be platinum-based. Entry into the trial is not limited to first line treatment for platinum-resistant ovarian cancer i.e. patients can have prior lines of therapy for platinum-resistant disease. 8. Ability to provide written informed consent prior to participating in the trial and any trial related procedures being performed 9. Adequate haematological and biochemical function as indicated below. These measurements must be performed within 7 days prior to randomisation: 9.1.Absolute neutrophil count >1.5 x 109/L 9.2. Platelet count >100 x 109/L 9.3. Haemoglobin >90 g/L 9.4. Serum creatinine <1.5 times ULN or creatinine clearance ≥50 mL/min (measured or calculated by Cockcroft and Gault equation/Wright formula – see Appendix 4); confirmation of creatinine clearance is only required when serum creatinine is >1.5 times the ULN 9.5. Total bilirubin <1.5 times ULN. In cases of Gilbert’s syndrome, bilirubin < 2 x ULN is allowed 9.6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or <5 times ULN in the presence of liver metastases 9.7. Alkaline phosphatase <5 x ULN 10. Willingness to comply with scheduled visits, treatment plans and laboratory tests and other study procedures 11. Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 7 days of trial treatment 11.1. Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, or, women under 50 years old who have been amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in the post-menopausal range for the institution OR 11.2. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation 12. Patients with synchronous tumours e.g. ovarian and endometrial or history of prior malignancy are eligible provided that there is biopsy evidence that the disease measurable on CT and/or MRI is ovarian in origin 13. Life expectancy of at least 12 weeks 14. ECOG Performance Status of 0,1
Key exclusion criteria	1. Non high grade serous histologies including carcinosarcoma. 2. Prior chemotherapy, biological therapy, radiation therapy, hormonal anti-cancer therapy, immunotherapy, other anticancer agents within 14 days of starting study treatment (not including palliative radiotherapy at focal sites). Treatment with any investigational agent within the preceding 4 weeks or within 5 half-lives of the investigational agent, whichever is longer. 3. Pregnant or lactating women 4. Women of childbearing age and potential who are not willing to use two highly effective forms of contraception as detailed in Section 8.2 (Pregnancy). In addition, patients will be excluded if they are not willing to use contraception for the duration as documented in Section 8.2 (Pregnancy) and Appendix I, Section 6.1 (Pregnancy – Duration of Contraception and Follow-up for Pregnancy). 5. With the exception of alopecia, any unresolved toxicities from prior chemotherapy should be no greater than CTCAE (Version 4.03) Grade 1 at the time of starting study treatment. 6. Major surgery within 4 weeks prior to entry to the study or minor surgery within 2 weeks of entry into the study (excluding placement of vascular access) 7. Spinal cord compression, known leptomeningeal involvement or brain metastases, unless treated and stable off steroids for at least 4 weeks prior to randomisation 8. Oral anticoagulants such as warfarin are not permitted, with the exception of 1mg daily warfarin dose for the prevention of Hickman line clotting. Anticoagulation with low molecular weight heparin is allowed. 9. Any haemopoietic growth factors (e.g., G-CSF, GM-CSF) and blood transfusions within 2 weeks prior to randomisation 10. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases e.g., severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease], uncontrolled chronic renal diseases (glomerulonephritis, nephritic syndrome, Fanconi Syndrome or Renal tubular acidosis), current unstable or uncompensated respiratory or cardiac conditions, uncontrolled hypertension, active bleeding diatheses or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required 11. Torsades de Pointes within 12 months of study entry 12. Judgment by the Investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements 13. Patients with a history of grade 3 or 4 allergic reaction (CTCAEv4.03) to paclitaxel are not permitted. Patients who have had prior grade 1 or 2 hypersensitivity reactions are permitted providing the weekly paclitaxel is administered using the desensitisation schedule (section 5.7.2) 14. Patients who have a new diagnosis of deep vein thrombosis or pulmonary embolism within 2 weeks of randomisation are permitted if clinically stable on a therapeutic dose of LMWH
Date of first enrolment	08/12/2015
Date of final enrolment	30/04/2018

Locations

Countries of recruitment

England
Northern Ireland
Scotland
United Kingdom

Study participating centres

The Beatson West of Scotland Cancer Centre

Glasgow
G12 0YN
United Kingdom

Belfast City Hospital

Belfast
BT9 7AB
United Kingdom

Dorset Cancer Centre

Poole
BH15 2JB
United Kingdom

Briston Oncology & Haematology Centre

Bristol
BS2 8ED
United Kingdom

Royal Preston Hospital

Preston
PR2 9HT
United Kingdom

Royal Sussex County Hospital

Sussex
BN2 1ES
United Kingdom

Birmingham City Hospital

Birmingham
B18 7QH
United Kingdom

Musgrove Park Hospital

Taunton
TA1 5DA
United Kingdom

Nottingham City Hospital

Nottingham
NG5 1PB
United Kingdom

St James University Hospital

Leeds
LS7 9TF
United Kingdom

Hammersmith Hospital

London
W12 0HS
United Kingdom

Weston Park Hospital

Sheffield
S10 2SJ
United Kingdom

Ninewells Hospital

Dundee
DD1 9SY
United Kingdom

Northampton General Hospital

Northampton
NN1 5BD
United Kingdom

Mount Vernon Hospital

Middlesex
HA6 2RN
United Kingdom

United College London Hospital

London
NW1 2BU
United Kingdom

The Royal Marsden Hospital

Surrey
SM2 5PT
United Kingdom

The Royal Marsden Hospital

London
SW3 6JJ
United Kingdom

Queen Elizabeth The Queen Mother

Kent
CT9 4AN
United Kingdom

Royal United Hospitals Bath NHS Foundation Trust

Bath
BA1 3NG
United Kingdom

Western General Hospital

Edinburgh
EH4 2XU
United Kingdom

Addenbrookes Hospital

Cambridge
CB2 0QQ
United Kingdom

Clatterbridge Centre for Oncology

Bebington
CH63 4JY
United Kingdom

Guys and St Thomas's NHS Foundation Trust

London
SE1 9RT
United Kingdom

Churchill Hospital

Oxford
OX3 7LE
United Kingdom

Sponsor information

NHS Greater Glasgow and Clyde
Hospital/treatment centre

c/o Research and Development
NHS Greater Glasgow & Clyde
1st Floor Tennent Institute
Western Infirmary
Church Street
Glasgow
G116NT
Scotland
United Kingdom

Website	http://www.nhsggc.org.uk/
"ROR"	https://ror.org/05kdz4d87

The University of Glasgow
University/education

c/o Research and Development
NHS Greater Glasgow & Clyde
1st Floor Tennent Institute
Western Infirmary
Church Street
Glasgow
G116NT
Scotland
United Kingdom

Funders

Funder type

Industry

Astra Zeneca

No information available

Results and Publications

Intention to publish date	31/12/2020
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
Publication and dissemination plan	Planned publications in a high-impact peer reviewed journal with the intent to publish 12 months after end of trial.
IPD sharing plan	The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Study outputs

Output type	Date created	Date added	Peer reviewed?	Patient-facing?
Abstract results	20/05/2017	12/05/2021	No	No
Abstract results	01/10/2019	12/05/2021	No	No
Results article	16/03/2023	20/03/2023	Yes	No
HRA research summary		28/06/2023	No	No

Editorial Notes

20/03/2023: Publication reference added.
12/05/2021: Abstract references added.
09/05/2017: The recruitment dates have been updated from 30/10/2015 - 27/02/2017 to 08/12/2015 - 30/04/2018 and the overall study end date has been updated from 30/10/2019 to 08/12/2019. In addition, the timepoints and methods of measurement have been added the the outcome measures and the publication and dissemination plan and IPD sharing plan have been added.
20/04/2016: Cancer Help UK lay summary link added.