Saracatinib (AZD0530) plus weekly paclitaxel in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer

ISRCTN	ISRCTN32163062
DOI	https://doi.org/10.1186/ISRCTN32163062
EudraCT/CTIS number	2009-017171-13
ClinicalTrials.gov number	NCT01196741
Secondary identifying numbers	8430

Submission date: 29/10/2010
Registration date: 29/10/2010
Last edited: 31/03/2022

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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-paclitaxel-saracatinib-ovarian-cancer-fallopian-tube-cancer-primary-peritoneal-cancer-sapproc

Study website

Contact information

Mr Lee Webber
Scientific

Cancer Research UK & UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom

Email	L.Webber@CTC.UCL.AC.UK

Study information

Study design	Multicentre randomised interventional treatment 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 the contact details below to request a patient information sheet
Scientific title	A randomised placebo-controlled trial of saracatinib (AZD0530) plus weekly paclitaxel in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer
Study acronym	SaPPrOC
Study objectives	This is a randomised, placebo-controlled double-blind trial. The overall aim is to investigate whether the addition of the Src inhibitor saracatinib (AZD0530) to weekly paclitaxel improves efficacy, compared with paclitaxel plus placebo, in patients with relapsed platinum-resistant ovarian cancer. The trial will also determine toxicity and ascertain whether the combination of paclitaxel plus saracatinib should proceed to a phase III trial.
Ethics approval(s)	Coventry & Warwickshire Research Ethics Committee, 04/08/2010, ref: 10/H1211/26
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: Gynaecological Cancer; Disease: Ovary
Intervention	Paclitaxel 80 mg/m2 (IV) to be given in 'cycles'. Each cycle will be 8 weeks of treatment, consisting of six weekly administrations of paclitaxel 80 mg/m2 followed by 2 weeks rest. Patients will receive four cycles to begin with. If there is evidence of ongoing response after four cycles, three further cycles will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after four cycles, treatment should be discontinued but may continue at the discretion of the Investigator. The maximum chemotherapy treatment period will be 56 weeks. Saracatinib (AZD0530). Patients will receive 175 mg/matched placebo daily. Administration will begin 1 week prior to commencement of paclitaxel chemotherapy, and will continue until the patient's disease progresses/relapses. Combined with chemotherapy, the maximum treatment period of saracatinib/placebo will be 57 weeks. Patients who progress/relapse during trial treatment will be taken off study and not followed up. Patients who do not relapse/progress during trial treatment will be followed up and offered saracatinib/placebo monotherapy. These patients will be followed up 6 weekly for 2 years or until progression, whichever is the sooner.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II/III
Drug / device / biological / vaccine name(s)	Saracatinib (AZD0530), paclitaxel
Primary outcome measure	Six-month progression-free survival (PFS), based on combined RECIST v1.1/GCIG CA125 criteria
Secondary outcome measures	1. Duration of response 2. Health Economics and Quality of Life outcomes based on FACT-O and EQ5D 3. Investigator Assessed PFS based on RECIST v1.1 4. Investigator Assessed Time to Progression 5. Objective Response Rate based on Investigator assessment using GCIG CA125 criteria and RECIST v1.1 6. Overall survival rate at 2 years 7. Safety and tolerability (toxicity) 8. Time to Progression based on RECIST v1.1
Overall study start date	01/11/2010
Completion date	01/05/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target number of participants	Planned sample size: 102; UK sample size: 102
Total final enrolment	107
Key inclusion criteria	1. Confirmed relapsed ovarian, fallopian tube or primary peritoneal cancer AND patients who have relapsed in the platinum-resistant (progression must not be based on CA125 alone) time-frame, i.e. have progressed within 6 months of platinum therapy 2. All patients must have formalin-fixed paraffin-embedded (FFPE) tissue available for translational research: this tissue may be tissue taken at original diagnosis 3. Patients need not have received prior taxane; if patients have received prior taxane, the interval since treatment must be known. Patients will be stratified as less than 6 months OR at least 6 months taxane interval/no prior taxane. 4. Patients will generally have received at least two lines of prior chemotherapy, but may enter if they have relapsed within 6 months of first-line therapy. Patients may have received prior liposomal doxorubicin, although this is NOT a requirement. The treatment immediately prior to study entry need not be platinum-based. 5. Measurable or evaluable disease (if not measurable by Response Evaluation Criteria in Solid Tumours version 1.1 [RECIST v1.1] criteria, must be evaluable by CA125 [GCIG criteria]) 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 - 2 7. Adequate haematological and biochemical function as follows: 7.1. Granulocyte count greater than 1.5 x 10^9/l 7.2. Platelet count greater than 100 x 10^9/l 7.3. Haemoglobin (Hb) greater than 9.0 g/dl 7.4. Serum creatinine less than 1.5 x upper limit of normal (ULN) 7.5. Bilirubin less than 1.5 x ULN. In cases of known Gilbert's syndrome, bilirubin less than 2 x ULN is allowed 7.6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) less than 2.5 x ULN 7.7. Alkaline phosphatase (ALP) less than 5 x ULN 7.8. Prothrombin and activated partial thromboplastin times less than 1.5 x ULN 8. Willingness to consent to take part in Level 1 of the translational sub-study, as per section 19.0 of the protocol (this is NOT optional)
Key exclusion criteria	1. Prior administration of weekly paclitaxel 2. Tumours of malignant mixed mesodermal (MMMT) or mucinous types 3. Unresolved bowel obstruction 4. Chemotherapy within the preceding 3 weeks 5. Radiotherapy within the preceding 3 weeks 6. Treatment with any investigational agent within the preceding 4 weeks or within 5 half-lives of the investigational agent, whichever is longer 7. Known leptomeningeal involvement or intracranial disease 8. Evidence of interstitial lung disease (bilateral, diffuse, parenchymal lung disease) 9. Resting electrocardiogram (ECG) with measurable QTc interval of greater than 480 msec at two or more time points within a 24-hour period 10. Pregnant or lactating females 11. Fertile women of childbearing potential not willing to use adequate contraception for the duration of trial treatment and for at least 30 days after the last administration of saracatinib +/- paclitaxel 12. Inability or unwillingness to give informed consent 13. Ongoing active infection or a documented history of human immunodeficiency virus (HIV) infection, hepatitis B or C 14. Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease 15. Concurrent autoimmune disorder, e.g. systemic lupus or any demyelinating disease 16. Use of immunosuppressive therapy or corticosteroids taken within the 4 weeks prior to study entry and during the treatment period
Date of first enrolment	01/11/2010
Date of final enrolment	01/05/2012

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Cancer Research UK & UCL Cancer Trials Centre

London
W1T 4TJ
United Kingdom

Sponsor information

University College London (UCL) (UK)
University/education

Gower Street
London
WC1E 6BT
England
United Kingdom

Website	http://www.ucl.ac.uk/
"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Industry

AstraZeneca
Government organisation / For-profit companies (industry)

Alternative name(s): AstraZeneca PLC, Pearl Therapeutics
Location: United Kingdom

Cancer Research UK- Clinical Trials Advisory and Awards Committee (CTAAC) grant (ref: C9423/A11569)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results				No	No
Results article	results	01/10/2014		Yes	No
Plain English results			31/03/2022	No	Yes
HRA research summary			28/06/2023	No	No

Editorial Notes

31/03/2022: Plain English results and total final enrolment added.
24/03/2016: added link to results - basic reporting.