Condition category
Cancer
Date applied
15/04/2015
Date assigned
15/04/2015
Last edited
22/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Dr Elizabeth Ward

ORCID ID

Contact details

Oncology Clinical Trials Office
University of Oxford
Old Road Campus Research Building
Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom
+44 (0)1865 617078
octo-scalop-2@oncology.ox.ac.uk

Type

Scientific

Additional contact

Dr Somnath Mukherjee

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

2013-004968-56

ClinicalTrials.gov number

NCT02024009

Protocol/serial number

18700

Study information

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

Acronym

SCALOP-2

Study hypothesis

Current 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

First MREC approval date 30/04/2015, ref: 15/SC/0103

Study design

Randomised; Interventional; Design type: Treatment

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 contact details to request a participant information sheet

Condition

Topic: Cancer; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Pancreas

Intervention

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

Phase

Phase II

Drug names

Gemcitabine, Nab-paclitaxel (Abraxane), Capecitebine, Nelfinavir

Primary outcome measures

Current 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

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 trial start date

31/10/2015

Overall trial end date

01/08/2020

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 27; UK Sample Size: 27

Participant 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 six 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 three 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 six 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)

Recruitment start date

08/03/2016

Recruitment end date

30/11/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Churchill Hospital
Oxford
OX3 7LE
United Kingdom

Trial participating centre

St. James University Hospital
Leeds
LS9 7TF
United Kingdom

Trial participating centre

Bristol Haematology & Oncology Centre
Bristol
BS2 8ED
United Kingdom

Trial participating centre

University College London
London
NW1 2BU
United Kingdom

Trial participating centre

Castle Hill Cancer Centre
Yorkshire
HU16 5JQ
United Kingdom

Trial participating centre

Hammersmith Hospital
London
W12 0HS
United Kingdom

Trial participating centre

Addenbrookes Hospital
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Royal Free Hospital
London
NW3 2QG
United Kingdom

Trial participating centre

Velindre Hospital
Cardiff
CF14 2TL
United Kingdom

Trial participating centre

Royal Surrey County Hospital
Surrey
GU2 7XX
United Kingdom

Trial participating centre

University Hospital Coventry
Coventry
CV2 2DX
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Clinical Trials and Research Governance (CTRG)
Joint Research Office
Block 60
Churchill Hospital
Headington
Oxford
OX3 7LE
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.admin.ox.ac.uk/researchsupport/ctrg/

Funders

Funder type

Charity

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Celgene Limited (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Publication summary

Publication citations

Additional files

Editorial Notes

22/04/2016: Plain English summary link added. On 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.