Contact information
Type
Scientific
Primary contact
Mr Lee Webber
ORCID ID
Contact details
Cancer Research UK & UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom
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L.Webber@CTC.UCL.AC.UK
Additional identifiers
EudraCT number
2009-017171-13
ClinicalTrials.gov number
NCT01196741
Protocol/serial number
8430
Study information
Scientific title
A randomised placebo-controlled trial of saracatinib (AZD0530) plus weekly paclitaxel in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer
Acronym
SaPPrOC
Study hypothesis
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
Coventry & Warwickshire Research Ethics Committee, 04/08/2010, ref: 10/H1211/26
Study design
Multicentre randomised interventional treatment trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Phase
Phase II/III
Drug names
Saracatinib (AZD0530), paclitaxel
Primary outcome measures
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 trial start date
01/11/2010
Overall trial end date
01/05/2012
Reason abandoned
Eligibility
Participant 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)
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
Planned sample size: 102; UK sample size: 102
Participant 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
Recruitment start date
01/11/2010
Recruitment end date
01/05/2012
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Cancer Research UK & UCL Cancer Trials Centre
London
W1T 4TJ
United Kingdom
Sponsor information
Organisation
University College London (UCL) (UK)
Sponsor details
Gower Street
London
WC1E 6BT
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Industry
Funder name
AstraZeneca
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United Kingdom
Funder name
Cancer Research UK- Clinical Trials Advisory and Awards Committee (CTAAC) grant (ref: C9423/A11569)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
See https://clinicaltrials.gov/ct2/show/results/NCT01196741
Publication summary
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25070546
Publication citations
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Results
McNeish IA, Ledermann JA, Webber L, James L, Kaye SB, Hall M, Hall G, Clamp A, Earl H, Banerjee S, Kristeleit R, Raja F, Feeney A, Lawrence C, Dawson-Athey L, Persic M, Khan I, A randomised placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer., Ann. Oncol., 2014, doi: 10.1093/annonc/mdu363.