Stereotactic body radiation therapy pre-operatively for borderline resectable pancreatic cancer

ISRCTN	ISRCTN14138956
DOI	https://doi.org/10.1186/ISRCTN14138956
ClinicalTrials.gov number	NCT02308722
Secondary identifying numbers	OCTO_054; 18496

Submission date: 18/03/2015
Registration date: 19/03/2015
Last edited: 02/03/2022

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

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-stereotactic-body-radiotherapy-before-surgery-for-pancreatic-cancer-sparc

Study website

Contact information

Mrs Elizabeth Ward
Scientific

Department of Oncology
Oncology Clinical Trials Office (OCTO)
University of Oxford
Old Road Campus Research Building
Roosevelt Drive
Oxford
OX3 7DQ
United Kingdom

Ms Stephanie Levy
Public

Oncology Clinical Trials Office (OCTO)
Department of Oncology
University of Oxford
Old Road Campus
Roosevelt Drive
Oxford
OX3 7DQ
United Kingdom

Phone	+44 (0)1865 617084
Email	stephanie.levy@oncology.ox.ac.uk

Study information

Study design	Non-randomised; Interventional; Design type: Treatment
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details to request a patient information sheet
Scientific title	A phase I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer
Study acronym	SPARC: SBRT pre-operatively for pancreatic cancer
Study objectives	This study aims to test the safety and efficacy of pre-operative stereotactic body radiation therapy (SBRT), and to establish the maximum tolerated dose (MTD) of margin-intensive SBRT delivered pre-operatively in the surgical management of pancreatic cancer.
Ethics approval(s)	NRES Committee South Central Oxford B, ref: 15/SC/0059
Health condition(s) or problem(s) studied	Topic: Cancer; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Pancreas
Intervention	Current interventions as of 10/05/2018: This is a single-arm prospective phase I dose escalation radiation study investigating 5-fraction stereotactic radiotherapy prior to planned surgical resection in borderline resectable or resectable pancreatic cancer. If we achieve the MTD then we will recruit up to 24 patients from 5 UK centres (Oxford, Leeds, Glasgow, Nottingham and Newcastle). Eligible patients will receive 5 fractions of stereotactic radiotherapy over 5-8 days, and surgery, if appropriate, will take place 5-6 weeks after radiotherapy. Patients will be on the study for approximately 36 weeks from registration on the study to the end of treatment visit (last protocol visit). Previous interventions: This is a single-arm prospective phase I dose escalation radiation study investigating 5-fraction stereotactic radiotherapy prior to planned surgical resection in borderline resectable pancreatic cancer. If we achieve the MTD then we will recruit up to 24 patients from 3 UK centres (Oxford, Leeds and Glasgow). Eligible patients will receive 5 fractions of stereotactic radiotherapy over 5-8 days, and surgery will take place 5-6 weeks after radiotherapy. Patients will be on the study for approximately 36 weeks from registration on the study to the end of treatment visit (last protocol visit).
Intervention type	Other
Primary outcome measure	Current primary outcome measure as of 10/05/2018: Maximum Tolerated Dose (MTD); Timepoint(s): 30 days post-surgery for patients proceeding to surgery or 3 months post SBRT for patients not proceeding to surgery. Previous primary outcome measure: Maximum Tolerated Dose (MTD); Timepoint(s): 30 days post-surgery
Secondary outcome measures	Current secondary outcome measures as of 10/05/2018: 1. Resection rates: Definitive resection rate. Timepoint(s) of evaluation of this end point - surgery 2. Resection margin status: R0/R1/R2 resection margin rates. Timepoint(s) of evaluation of this end point - pathological specimen evaluated at surgery 3. Response rates: Rate of pathological complete response. Timepoint(s) of evaluation of this end point - pathological specimen evaluation post operation 4. Late SBRT toxicity (>1 month to 6 months post-surgery or to 6 months post SBRT for patients not proceeding to surgery): Any Late GI AE/other AE > grade 2 CTCAE v4.03. Timepoint(s) of evaluation of this end point - post-surgery visits >1 month, 3 months and 6 months or 3 and 6 months post-SBRT for patients not proceeding to surgery 5. Efficacy and long term safety of SBRT delivered pre-operatively in the management of pancreatic cancer: Overall survival and progression free survival at 12 and 24 months post D1 SBRT. Timepoint(s) of evaluation of this end point -12 and 24m FU 6. To investigate if a relationship between imaging and pathology can be established: Differences between R0 as predicted by CT + MRI + PET pre-SBRT, post-SBRT and pathology findings. Timepoint(s) of evaluation of this end point - post-surgery 7. To explore possible immune-related responses to SBRT in pancreatic cancer: Changes in levels of interferon-related RNA and cytological markers of the innate and adaptive immune response before and during SBRT in pancreatic cancer. Timepoint(s) of evaluation of this end point - before, during and after SBRT Previous secondary outcome measures: 1. Resection rates: Definitive resection rate. Timepoint(s) of evaluation of this end point - surgery 2. Resection margin status: R0/R1/R2 resection margin rates. Timepoint(s) of evaluation of this end point - pathological specimen evaluated at surgery 3. Response rates: Rate of pathological complete response. Timepoint(s) of evaluation of this end point - pathological specimen evaluation post operation 4. Late SBRT toxicity (>1 month to 6 months post-surgery): Any Late GI AE/other AE > grade 2 CTCAE v4.03. Timepoint(s) of evaluation of this end point - post-surgery visits >1 month, 3 months and 6 months 5. Efficacy and long term safety of SBRT delivered pre-operatively in the management of pancreatic cancer: Overall survival and progression free survival at 12 and 24 months post D1 SBRT. Timepoint(s) of evaluation of this end point -12 and 24m FU 6. To investigate if a relationship between imaging and pathology can be established: Differences between R0 as predicted by CT + MRI + PET pre-SBRT, post-SBRT and pathology findings. Timepoint(s) of evaluation of this end point - post-surgery 7. To explore possible immune-related responses to SBRT in pancreatic cancer: Changes in levels of interferon-related RNA and cytological markers of the innate and adaptive immune response before and during SBRT in pancreatic cancer. Timepoint(s) of evaluation of this end point - before, during and after SBRT
Overall study start date	01/11/2014
Completion date	01/03/2019

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target number of participants	Planned Sample Size: 24; UK Sample Size: 24
Total final enrolment	12
Key inclusion criteria	Current participant inclusion criteria as of 10/05/2018: 1. Borderline resectable localised tumour of the pancreatic head/uncinate process/body as per NCCN Guidelines (tumours of the tail of pancreas are not eligible for inclusion) or operable tumour in contact with or operable tumour in contact with, as defined by CT +/MRI +/PET criteria within 28+/7 days prior to trial entry de novo or following chemotherapy. 2. Histologically proven pancreatic ductal adenocarcinoma or cytological proven pancreatic malignancy 3. Able to undergo biliary drainage using a stent 4. Deemed fit and suitable for surgical resection 5. No overt metastases or uncertain status with investigations suspicious of possible metastatic disease (e.g. small equivocal pulmonary nodule(s)). 6. Male or female, Age = 16 years 7. Life expectancy of at least 6 months 7. ECOG performance status 0-1 8. The patient is willing and able to comply with the protocol for the duration of the study, and scheduled followup visits and examinations 9. Written (signed and dated) informed consent and be capable of cooperating with protocol 10. Haematological and biochemical indices within given ranges Previous participant inclusion criteria: 1. Borderline resectable localised tumour of the pancreatic head/uncinate process/body as per NCCN Guidelines (tumours of the tail of pancreas are not eligible for inclusion) as defined by CT +/MRI +/PET criteria within 28+/7 days prior to trial entry 2. Histologically proven pancreatic ductal adenocarcinoma or cytological proven pancreatic malignancy 3. Able to undergo biliary drainage using a stent 4. Deemed fit and suitable for surgical resection 5. Male or female, Age = 16 years 6. Life expectancy of at least 6 months 7. ECOG performance status 0-1 8. The patient is willing and able to comply with the protocol for the duration of the study, and scheduled followup visits and examinations 9. Written (signed and dated) informed consent and be capable of cooperating with protocol 10. Haematological and biochemical indices within given ranges
Key exclusion criteria	Current participant exclusion criteria as of 10/05/2018: 1. Definite metastatic disease or local disease that cannot be encompassed in the SBRT field 2. History of previous or concurrent malignancy diagnoses for which the expected prognosis is likely to be worse than that of the current diagnosis of pancreatic cancer (excludes for example: e.g. localised prostate cancer, early colorectal cancer, early breast cancer, curatively-treated basal cell carcinoma of skin, carcinoma in situ of cervix; curatively treated cancer of other sites who are recurrence free for >3 years) 3. Serious medical or psychological condition precluding trial intervention 4. Previous upper abdominal or chest wall radiotherapy 5. Pregnancy. Pregnant or breastfeeding women or women of childbearing potential unless effective methods of contraception are used. 6. Any other psychological, social or medical condition, physical examination finding or laboratory abnormality that the Investigator considers makes the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of the trial results. Previous participant exclusion criteria: 1. Distant metastatic disease or local disease that cannot be encompassed in the SBRT field 2. History of previous or concurrent malignancy diagnoses (except curatively-treated basal cell carcinoma of skin, carcinoma in situ of cervix; curatively treated cancer of other sites who are recurrence free for ≥ 3 years) 3. Serious medical or psychological condition precluding neoadjuvant treatment and surgical resection 4. Previous upper abdominal or chest wall radiotherapy 5. Pregnancy. Pregnant or breastfeeding women or women of childbearing potential unless effective methods of contraception are used 6. Any other psychological, social or medical condition, physical examination finding or laboratory abnormality that the Investigator considers makes the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of the trial results.
Date of first enrolment	17/04/2015
Date of final enrolment	22/03/2018

Locations

Countries of recruitment

England
Scotland
United Kingdom

Study participating centres

Churchill Hospital

Oxford
OX3 9DU
United Kingdom

The Beatson West of Scotland Cancer Centre

Glasgow
G12 0YN
United Kingdom

Leeds Cancer Centre

Leeds
LS9 7TF
United Kingdom

Nottingham University Hospitals

Nottingham
NG5 1PB
United Kingdom

Freeman Hospital

Newcastle
NE7 7DN
United Kingdom

Sponsor information

University of Oxford
University/education

c/o Ms Heather House
University of Oxford Clinical Trials and Research Governance Team
Joint Research Office Block 60
Churchill Hospital
Oxford
OX3 7LE
England
United Kingdom

Website	https://www.admin.ox.ac.uk/researchsupport/ctrg/
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Government

Cancer Research UK
Private sector organisation / Other non-profit organizations

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

Results and Publications

Intention to publish date	31/01/2019
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
Publication and dissemination plan	Data from all sites will be analysed together and published as soon as possible. Individual participating PIs may not publish data concerning their participants which are directly relevant to questions posed by the trial until the TMG has published its report. The TMG will form the basis of the writing committee and advise on the nature of publications, subject to the Sponsor’s requirements.
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	13/09/2016		Yes	No
Abstract results	abstract	01/02/2018		No	No
Results article	results	01/02/2021	29/09/2021	Yes	No
Plain English results		01/03/2022	02/03/2022	No	Yes
HRA research summary			28/06/2023	No	No

Editorial Notes

02/03/2022: The Cancer Research UK lay results summary has been added.
04/10/2021: The following changes have been made:
1. The trial website has been updated.
2. The participant level data has been changed from 'Not provided at time of registration' to 'Not expected to be available'.
29/09/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
07/06/2019: Publication reference added.
10/05/2018: The following changes have been made:
1. Stephanie Levy has been added as the primary contact.
2. The scientific title has been changed from "A phase I trial of pre-operative, margin intensive, stereotactic body radiation therapy for previously untreated borderline resectable pancreatic cancer" to "A phase I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer".
3. The acronym has been changed from "SPARC: SBRT pre-operatively for borderline resectable pancreatic cancer" to "SPARC: SBRT pre-operatively for pancreatic cancer".
4. The interventions have been changed.
5. The primary outcome measure has been changed.
6. The secondary outcome measures have been changed.
7. The overall trial end date has been changed from 31/01/2018 to 01/03/2019.
8. The participant inclusion criteria have been changed.
9. The participant exclusion criteria have been changed.
10. The recruitment end date has been changed from 31/03/2017 to 22/03/2018.
11. Nottingham University Hospitals and Freeman Hospital have been added as trial centres.
14/09/2016: Publication reference added.