Condition category
Cancer
Date applied
20/10/2015
Date assigned
21/10/2015
Last edited
20/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Ms Liz-Anne Lewsley

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

2014-005221-12

ClinicalTrials.gov number

Protocol/serial number

OCTOPUS-2014

Study information

Scientific title

A randomised phase II umbrella trial of weekly paclitaxel +/- novel agents in platinum-resistant ovarian cancer

Acronym

OCTOPUS

Study hypothesis

We hypothesise that 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

Brighton and Sussex NRES Committee, 09/10/2015, ref:15/LO/1302

Study design

Randomised, placebo-controlled, double blind multi centre trial

Primary study design

Interventional

Secondary study design

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

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

Phase

Phase II

Drug names

1. Paclitaxel
2. AZD2014

Primary outcome measures

Progression-free survival (PFS) based on combined RECIST v1.1/GCIG CA125 criteria

Secondary outcome measures

1. Response (based on RECIST 1.1 and GCIG CA125 criteria)
2. Overall survival
3. Safety and tolerability
4. Quality of life (QoL)
5. Resource use for health economic assessment

Overall trial start date

30/10/2015

Overall trial end date

30/10/2019

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

140

Participant 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

Recruitment start date

30/10/2015

Recruitment end date

27/02/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

The Beatson West of Scotland Cancer Centre
Glasgow
G12 0YN
United Kingdom

Trial participating centre

Belfast City Hospital
Belfast
BT9 7AB
United Kingdom

Trial participating centre

Dorset Cancer Centre
Poole
BH15 2JB
United Kingdom

Trial participating centre

Briston Oncology & Haematology Centre
Bristol
BS2 8ED
United Kingdom

Trial participating centre

Royal Preston Hospital
Preston
PR2 9HT
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Sussex
BN2 1ES
United Kingdom

Trial participating centre

Birmingham City Hospital
Birmingham
B18 7QH
United Kingdom

Trial participating centre

Musgrove Park Hospital
Taunton
TA1 5DA
United Kingdom

Trial participating centre

Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

St James University Hospital
Leeds
LS7 9TF
United Kingdom

Trial participating centre

Hammersmith Hospital
London
W12 0HS
United Kingdom

Trial participating centre

Weston Park Hospital
Sheffield
S10 2SJ
United Kingdom

Trial participating centre

Ninewells Hospital
Dundee
DD1 9SY
United Kingdom

Trial participating centre

Northampton General Hospital
Northampton
NN1 5BD
United Kingdom

Trial participating centre

Mount Vernon Hospital
Middlesex
HA6 2RN
United Kingdom

Trial participating centre

United College London Hospital
London
NW1 2BU
United Kingdom

Trial participating centre

The Royal Marsden Hospital
Surrey
SM2 5PT
United Kingdom

Trial participating centre

The Royal Marsden Hospital
London
SW3 6JJ
United Kingdom

Trial participating centre

Queen Elizabeth The Queen Mother
Kent
CT9 4AN
United Kingdom

Trial participating centre

Royal United Hospitals Bath NHS Foundation Trust
Bath
BA1 3NG
United Kingdom

Trial participating centre

Western General Hospital
Edinburgh
EH4 2XU
United Kingdom

Trial participating centre

Addenbrookes Hospital
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Clatterbridge Centre for Oncology
Bebington
CH63 4JY
United Kingdom

Trial participating centre

Guys and St Thomas's NHS Foundation Trust
London
SE1 9RT
United Kingdom

Trial participating centre

Churchill Hospital
Oxford
OX3 7LE
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow and Clyde

Sponsor details

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

Sponsor type

Hospital/treatment centre

Website

Organisation

The University of Glasgow

Sponsor details

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

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

Astra Zeneca

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

20/04/2016: Cancer Help UK lay summary link added.