Systemic therapy and chemoradiation in advanced localised pancreatic cancer (SCALOP2)
| ISRCTN | ISRCTN50083238 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN50083238 |
| EudraCT/CTIS number | 2013-004968-56 |
| ClinicalTrials.gov number | NCT02024009 |
| Secondary identifying numbers | CPMS 18700 |
- Submission date
- 15/04/2015
- Registration date
- 15/04/2015
- Last edited
- 29/07/2024
- 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
Contact information
Dr Rachel Shaw
Public
Public
Oncology Clinical Trials Office (OCTO)
University of Oxford
Old Road Campus Research Building
Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom
| Phone | +44 (0)1865 617078 |
|---|---|
| octo-scalop-2@oncology.ox.ac.uk |
Prof Somnath Mukherjee
Scientific
Scientific
Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology
University of Oxford
Old Road Campus Research Building
Off Roosevelt Drive
Oxford
OX3 7DQ
United Kingdom
Study information
| Study design | Randomized; Interventional; Design type: Treatment |
|---|---|
| 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 contact details to request a participant information sheet |
| Scientific title | A multi-centre randomised study of induction chemotherapy followed by capecitabine (+/-nelfinavir) with high or standard dose radiotherapy for locally advanced non-metastatic pancreatic cancer |
| Study acronym | SCALOP-2 |
| Study objectives | Current hypothesis as of 06/02/2020: Stage 1: To determine the Maximum Tolerated Dose (MTD) of nelfinavir to be administered alongside chemoradiotherapy and therefore to establish the dose of nelfinavir to be taken forward into Stage 2. Stage 2: 2.1. Does increasing radiotherapy dose schedule from 50.4Gy (in 28 fractions) to 60Gy (in 30 fractions) improve overall survival (OS) in LANPC? 2.2. Does the addition of nelfinavir to CRT improve progression free survival (PFS) in LANPC? _____ Previous hypothesis as of 22/10/2015: Stage 1: To determine the Maximum Tolerated Dose (MTD) of nelfinavir to be administered alongside chemoradiotherapy and therefore to establish the dose of nelfinavir to be taken forward into Stage 2. Stage 2: 2.1. Does increasing radiotherapy dose schedule from 50.4Gy (in 28 fractions) to 60Gy (in 30 fractions) improve the 12 month overall survival (OS) rate? 2.2. Does the addition of nelfinavir to CRT improve the progression free survival (PFS) in LANPC? _____ Previous hypothesis: Stage 1: To determine a safe and tolerable dose of nelfinavir to be administered alongside chemo-radiotherapy and therefore to establish the dose of nelfinavir to be taken forward into Stage 2. Stage 2: 2.1. Does increasing radiotherapy dose schedule from 50.4Gy (in 28 fractions) to 60Gy (in 30 fractions) improve the 12 month overall survival (OS) rate? 2.2. Does the addition of nelfinavir to CRT improve the progression free survival (PFS) in LANPC? |
| Ethics approval(s) | First MREC approval date 30/04/2015, ref: 15/SC/0103 |
| Health condition(s) or problem(s) studied | Pancreatic cancer |
| Intervention | Current interventions as of 06/02/2020: 1. Arm A: One cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + nelfinavir** + 50.4Gy in 28# 2. Arm B: One cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + 50.4Gy in 28# 3. Arm C: One cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + nelfinavir** + 60Gy in 30# 4. Arm D: One cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + 60Gy in 30# *One cycle GEMABX = 28 day cycle of intravenous nab-paclitaxel 125mg/m2 followed by gemcitabine 1000mg/m2 on day 1, 8 and 15. **Participants on nelfinavir arms will commence nelfinavir 7 days before start of chemoradiation and take nelfinavir 7 days per week during radiotherapy. _____ Previous interventions: 1. Arm A: One cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + nelfinavir** + 50.4Gy in 28# 2. Arm B: One cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + 50.4Gy in 28# 3. Arm C: One cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + nelfinavir** + 60Gy in 30# 4. Arm D: One cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + 60Gy in 30# 5. Arm E: Three cycles of GEMABX* *One cycle GEMABX = 28 day cycle of intravenous nab-paclitaxel 125mg/m2 followed by gemcitabine 1000mg/m2 on day 1, 8 and 15. **Participants on nelfinavir arms will commence nelfinavir 7 days before start of chemoradiation and take nelfinavir 7 days per week during radiotherapy. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Gemcitabine, nab-paclitaxel (abraxane), capecitabine, nelfinavir |
| Primary outcome measure | Current primary outcome measures as of 06/02/2020: Stage 1: Maximum Tolerated Dose (MTD) and safety Stage 2: Co‐primary outcome measures: 1. Concurrent biological question (± Nelfinavir): Progression free Survival (PFS) (time from registration to event(progression)) 2. RT dose question (50.4Gy v 60Gy): Overall survival (OS) in LANPC _____ Previous primary outcome measures as of 22/10/2015: Stage 1: Maximum Tolerated Dose (MTD) and safety Stage 2: Co‐primary outcome measures: 1. Concurrent biological question (± Nelfinavir): Progression free Survival (PFS) (time from registration to event(progression)) 2. RT dose question (50.4Gy v 60Gy): 12 month overall survival (OS) rate _____ Previous primary outcome measures: Stage 1: A safe and tolerable dose of nelfinavir to be administered alongside chemoradiotherapy in Stage 2. Stage 2: Co-primary outcome measures: 1. Concurrent biological question (+/- Nelfinavir): Progression free Survival (PFS) (time from registration to event (progression)) 2. RT dose question (50.4Gy v 60Gy): 12 month overall survival (OS) rate |
| Secondary outcome measures | Current secondary outcome measures as of 06/02/2020: Stage 2: Secondary outcome measures: 1. Concurrent biological question: Toxicity, compliance, overall survival, resection rates 2. RT dose question: PFS, 12-month OS rate, resection rates, toxicity 3. Quality of Life 4. CA19-9 level, 1-year local control rate 5. Disease response _____ Previous secondary outcome measures: Stage 2: Secondary outcome measures: 1. Concurrent biological question: Toxicity, compliance, overall survival, resection rates 2. RT dose question: PFS, resection rates 3. CRT/no CRT question (Arms A+B+C+D v Arm E): PFS, Toxicity, compliance, overall survival, 4. Resection rate and QoL with the addition of CRT: Resection rates, QoL 5. CA19-9 level, local control rate 6. Concordance to RT planning protocol between 50Gy and 60Gy 7. Objective disease response |
| Overall study start date | 04/03/2016 |
| Completion date | 31/05/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 27; UK Sample Size: 27; Stage 2: 168 |
| Total final enrolment | 186 |
| Key inclusion criteria | Current inclusion criteria as of 06/02/2020: 1. Aged 18 years or over 2. Histologically or cytologically proven carcinoma of the pancreas 3. Locally advanced, non-metastatic inoperable disease as per NCCN criteria. The following types of interventions are allowed: 3.1. Palliative bypass procedure 3.2. Common bile duct stenting 4. Primary pancreatic lesion 6 cm or less in diameter (taken from scan results) 5. World Health Organisation PS 0-1 6. Adequate haematological function: neutrophils at least 1.5 x 109/L and platelets at least 100 x 109/L 7. Adequate liver function tests: 7.1. Serum bilirubin less than or equal to 1.5 x ULN. In participants who have had a recent biliary drain and whose bilirubin is improving, a value of less than or equal to 3 x ULN is acceptable, however treatment should not start unless Bilirubin is less than or equal to 1.5 x ULN. 7.2. AST and/or ALT less than or equal to 3 x ULN. 8. Adequate renal function (GFR at least 40ml/min) (using a validated creatinine clearance calculation (e.g. Cockcroft & -Gault , Wright formula, or as per local standard). 9. Written informed consent obtained 10. Women of child-bearing potential must have negative serum or urine pregnancy test within 14 days prior to registration and must agree to use an adequate contraception method (defined as barrier methods in conjunction with spermicide, approved contraceptive implants, long-term injectable contraception or intrauterine hormonal devices) during GEMABX treatment and for 6 months after the last administration of GEMABX, as well as during chemoradiotherapy and for 6 months after completion of all treatment. 11. Male patients must be surgically sterile or must agree to use a condom during GEMABX treatment and for 6 months after last administration of GEMABX, and to use a condom during chemoradiotherapy and for three months after completion of chemoradiotherapy or, whichever date comes last. _____ Previous inclusion criteria: 1. Aged 18 years or over 2. Histologically or cytologically proven carcinoma of the pancreas 3. Locally advanced, non-metastatic inoperable disease as per NCCN criteria. The following types of interventions are allowed: 3.1. Palliative bypass procedure 3.2. Common bile duct stenting 4. Primary pancreatic lesion 6 cm or less in diameter (taken from scan results) 5. WHO PS 0-1 6. Adequate haematological function: neutrophils at least 1.5 x 109/L, platelets at least 100 x 109/L and haemoglobin at least 100g/L 7. Adequate liver function tests: 7.1. Serum bilirubin less than or equal to 1.5 x ULN. In participants who have had a recent biliary drain and whose bilirubin is improving, a value of less than or equal to 3 x ULN is acceptable, however treatment should not start unless Bilirubin is less than or equal to 1.5 x ULN. 7.2. AST and/or ALT less than or equal to 3 x ULN. 8. Adequate renal function (GFR at least 50ml/min) 9. Written informed consent obtained 10. Women of child‐bearing potential must have negative serum or urine pregnancy test within 14 days prior to registration, must agree to use a highly effective contraception method during GEMABX treatment and for 30 days after last administration of GEMABX and to use an acceptable contraception method during chemoradiotherapy and for 6 months after completion of all treatment 11. Male patients must be surgically sterile or must agree to use a condom during GEMABX treatment and for 90 days after last administration of GEMABX, and to use a condom during chemoradiotherapy and for three months after completion of chemoradiotherapy |
| Key exclusion criteria | Current exclusion criteria as of 06/02/2020: 1. Primary resectable cancer of the pancreas. 2. Distant metastases 3. Pregnant or breastfeeding patients. 4. Any evidence of severe uncontrolled systemic diseases including uncontrolled coronary artery disease, myocardial infarction or stroke within the last 6 months, any major systemic or psychiatric comorbidities or any other considerations that the PI judges might impact on patient safety or protocol compliance and achievement of the study aims. 5. Previous malignancies in the preceding 3 years except for: 5.1. In situ cancer of the uterine cervix 5.2. Adequately treated basal cell skin carcinoma 5.3. Adequately treated early-stage non-pancreatic malignancy in complete remission for at least three years 6. Renal abnormalities including adult polycystic kidney disease or hydronephrosis or ipsilateral single kidney (i.e. functioning right kidney for head tumours; left kidney for tail tumours) that may preclude upper abdominal radiotherapy without damaging functional kidneys. 7. Previous RT to upper abdomen 8. Recurrent cancer following definitive pancreatic surgery 9. Lymphoma or neuroendocrine tumours of the pancreas 10. Known haemophilia A and B, chronic hepatitis type B or C. 11. Other experimental treatment 6 weeks or less prior to registration into this study (including chemotherapy and immunotherapy). 12. Known hypersensitivity to any of the IMPs or any of their excipients. 13. Known dihydropyrimidine dehydrogenase (DPD) deficiency 14. Known galactose intolerance, Lapplactose deficiency or glucosegalactose malabsorption 15. History of severe unexpected reaction to fluoropyrimidine therapies 16. If the following concomitant medications cannot be discontinued temporarily during the CRT phase then the patients cannot enter the trial, as they interact with capecitabine: 16.1. Sorivudine and analogues e.g. brivudine 16.2. Methotrexate. 16.3. Allopurinol and dipyridamole 17. Use of prohibited concomitant medications listed in section 7.3.4. (Note that temporary discontinuation during nelfinavir treatment is not acceptable) these cannot be temporarily discontinued. Please refer to the following website for full information: http://www.viivhealthcare.com/our-medicines/viracept.aspx 18. Known HIV-positive disease (but routine screening for HIV is not required) _____ Previous exclusion criteria: 1. Primary resectable cancer of the pancreas. 2. Distant metastases 3. Pregnant or breastfeeding patients. 4. Any evidence of severe uncontrolled systemic diseases including uncontrolled coronary artery disease, myocardial infarction or stroke within the last 6 months, any major systemic or psychiatric comorbidities or any other considerations that the PI judges might impact on patient safety or protocol compliance and achievement of the study aims. 5. Previous malignancies in the preceding 3 years except for: 5.1. In situ cancer of the uterine cervix 5.2. Adequately treated basal cell skin carcinoma 5.3. Adequately treated early stage non-pancreatic malignancy in complete remission for at least 3 years 6. Renal abnormalities including adult polycystic kidney disease or hydronephrosis or ipsilateral single kidney (i.e. functioning right kidney for head tumours; left kidney for tail tumours) that may preclude upper abdominal radiotherapy without damaging functional kidneys. 7. Previous RT to upper abdomen 8. Recurrent cancer following definitive pancreatic surgery 9. Lymphoma or neuroendocrine tumours of the pancreas 10. Known haemophilia A and B, chronic hepatitis type B or C. 11. Other experimental treatment 6 weeks or less prior to registration into this study (including chemotherapy and immunotherapy). 12. Known hypersensitivity to any of the IMPs or any of their excipients. 13. Known dihydropyrimidine dehydrogenase (DPD) deficiency 14. Known galactose intolerance, Lapplactose deficiency or glucosegalactose malabsorption 15. History of severe unexpected reaction to fluoropyrimidine therapies 16. If the following concomitant medications cannot be discontinued temporarily during the CRT phase then the patients cannot enter the trial: 16.1. Sorivudine and analogues e.g. brivudine 16.2. Methotrexate 16.3. Allopurinol and dipyridamole 17. Known HIV positive disease (but routine screening for HIV is not required) |
| Date of first enrolment | 08/03/2016 |
| Date of final enrolment | 27/04/2020 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
OX3 7LE
United Kingdom
St. James University Hospital
Leeds
LS9 7TF
United Kingdom
LS9 7TF
United Kingdom
University College London
London
NW1 2BU
United Kingdom
NW1 2BU
United Kingdom
Addenbrookes Hospital
Cambridge
CB2 0QQ
United Kingdom
CB2 0QQ
United Kingdom
Velindre Hospital
Cardiff
CF14 2TL
United Kingdom
CF14 2TL
United Kingdom
Aberdeen Royal Infirmary
Aberdeen
AB25 2ZN
United Kingdom
AB25 2ZN
United Kingdom
Belfast City Hospital
51 Lisburn Road
Belfast
BT9 7AB
United Kingdom
Belfast
BT9 7AB
United Kingdom
Bristol Haematology and Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom
Bristol
BS2 8ED
United Kingdom
Queen’s Centre for Oncology and Haematology
Hull
HU16 5JQ
United Kingdom
HU16 5JQ
United Kingdom
Nottingham University Hospitals City Hospital Campus
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Clatterbridge Cancer Centre
Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom
Bebington
Wirral
CH63 4JY
United Kingdom
Colchester General Hospital
Colchester
CO4 5JL
United Kingdom
CO4 5JL
United Kingdom
Derriford Hospital
Plymouth
PL6 8DH
United Kingdom
PL6 8DH
United Kingdom
Hammersmith Hospital
London
W12 0HS
United Kingdom
W12 0HS
United Kingdom
Milton Keynes Hospital
Milton Keynes
MK6 5LD
United Kingdom
MK6 5LD
United Kingdom
Norfolk and Norwich University Hospital
Norwich
NR4 7UY
United Kingdom
NR4 7UY
United Kingdom
North Middlesex Hospital
London
N18 1QX
United Kingdom
N18 1QX
United Kingdom
Royal Free Hospital
London
NW3 2QG
United Kingdom
NW3 2QG
United Kingdom
Royal Surrey County Hospital
Surrey
GU2 7XX
United Kingdom
GU2 7XX
United Kingdom
The Christie Hospital
Manchester
M20 4BX
United Kingdom
M20 4BX
United Kingdom
United Lincolnshire Hospital
Lincoln
LN2 5QY
United Kingdom
LN2 5QY
United Kingdom
University Hospital Coventry
Coventry
CV2 2DX
United Kingdom
CV2 2DX
United Kingdom
Weston Park Hospital
Sheffield
S10 2SJ
United Kingdom
S10 2SJ
United Kingdom
Sponsor information
University of Oxford (UK)
Hospital/treatment centre
Hospital/treatment centre
Clinical Trials and Research Governance (CTRG)
Joint Research Office
Block 60, Churchill Hospital
Headington
Oxford
OX3 7LE
England
United Kingdom
| Website | http://www.admin.ox.ac.uk/researchsupport/ctrg/ |
|---|---|
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Charity
Cancer Research UK
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Celgene Limited (UK)
No information available
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 |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 04/02/2019 | 09/08/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 23/07/2024 | 29/07/2024 | Yes | No |
Editorial Notes
29/07/2024: Publication reference and total final enrolment added.
08/09/2023: CRUK link added to PES field.
10/06/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/05/2020 to 27/04/2020.
2. The overall end date was changed from 01/11/2021 to 31/05/2021.
3. Recruitment has now ended.
05/05/2020: Due to current public health guidance, recruitment for this study has been paused.
06/02/2020: The following changes were made to the trial record:
1. The trial website was added.
2. The public contact was updated.
3. The hypothesis was changed.
4. The interventions were changed.
5. The primary outcome measure was changed.
6. The secondary outcome measures were changed.
7. The overall start date was changed from 31/10/2015 to 04/03/2016.
8. The overall end date was changed from 01/08/2020 to 01/11/2021.
9. The inclusion criteria were changed.
10. The exclusion criteria were changed.
11. The recruitment end date was changed from 30/11/2019 to 31/05/2020.
12. The sponsor address was updated.
13. The trial participating centres Aberdeen Royal Infirmary, Belfast City Hospital, Nottingham City Hospital, Clatterbridge Cancer Centre, Colchester General Hospital, Derriford Hospital, Milton Keynes Hospital, Norfolk and Norwich University Hospital, North Middlesex Hospital, The Christie Hospital, United Lincolnshire Hospital, Weston Park Hospital were added.
14. The total target enrolment was changed from 27 to 195.
09/08/2019: Publication reference added.
03/04/2019: The condition has been changed from "Topic: Cancer; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Pancreas" to "Pancreatic cancer" following a request from the NIHR.
22/04/2016: Plain English summary link added.
09/03/2016: The recruitment start date was changed from 30/11/2015 to 08/03/2016.
22/10/2015: The following changes were made to the trial record:
1. The overall trial start date was changed from 01/05/2015 to 31/10/2015.
2. The overall trial end date was changed from 01/05/2019 to 01/08/2020.
