Condition category
Cancer
Date applied
29/10/2010
Date assigned
29/10/2010
Last edited
24/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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
-
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

http://www.ucl.ac.uk/

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)

CRUK

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

  1. 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.

Additional files

Editorial Notes

24/03/2016: added link to results - basic reporting.