Sponsor: University of Oxford
ClinicalTrials.gov Number: NCT02024009
EudraCT number: 2013-004968-56
Systemic therapy and Chemoradiation in Advanced LOcalised Pancreatic cancer – 2
Full 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
Stage 1: Rolling six dose finding safety run-in that will determine the Maximum Tolerated Dose (MTD) of nelfinavir in combination with capecitabine and 50.4Gy in 28 fractions of RT and to establish the dose to take forward to Stage 2.
Stage 2: Open label, randomised clinical trial with 2 x 2 factorial + chemotherapy-only arm + observation cohort. This will commence following successful completion of Stage 1 (safety run-in). The final dose of nelfinavir used in the randomised phase will be determined in the safety run‐in.
Patients with locally advanced, non-metastatic, inoperable pancreatic cancer
Stage 1 open to recruitment
- Stage 1: 27 patients enrolled (up to 18 treated with nelfinavir)
- Stage 2: 262 patients enrolled (170 randomised)
Stage 1 current recruitment: 1 patient (May 2016)
Stage 1 sites in recruitment:
- Churchill Hospital, Oxford University Hospitals Trust
- Bristol Haematology and Oncology Centre, Bristol University Hospitals Bristol NHS Foundation Trust
- Velindre Cancer Centre, Cardiff, Velindre NHS Trust
Stage 1 sites in set-up:
Castle Hill Cancer Centre, Hull
Hammersmith Hospital, London
Royal Free Hospital, London
Royal Surrey County, Guildford
St James University Hospital, Leeds
University College London, London
University Hospital, Coventry
Participants meeting the following criteria may be included in the trial:
- Aged 18 years or over
- Histologically or cytologically proven carcinoma of the pancreas
- Locally advanced, non-metastatic inoperable disease as per NCCN criteria. The following types of interventions are allowed:
- Palliative bypass procedure
- Common bile duct stenting
- Primary pancreatic lesion 6 cm or less in diameter (taken from scan results)
- Wolrd Health Organisation Performance Status 0-1
- Adequate haematological function: neutrophils ≥1.5 x 109/L, platelets ≥100 x 109/L and haemoglobin ≥100g/L
- Adequate liver function tests:
- Serum bilirubin ≤1.5 x ULN. In participants who have had a recent biliary drain and whose bilirubin is improving, a value of ≤3 x ULN is acceptable, however treatment should not start unless Bilirubin is ≤1.5 x ULN.
- AST and/or ALT ≤3 x ULN.
- Adequate renal function (GFR ≥ 50ml/min (Cockcroft & Gault)
- Written informed consent obtained
- 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) which must be continued for 6 months after completion of all treatment.
- 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.
If any of the following criteria apply, patients cannot be included in the trial:
- Primary resectable cancer of the pancreas.
- Distant metastases
- Pregnant or breast-feeding patients.
- 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 co-morbidities or any other considerations that the PI judges might impact on patient safety or protocol compliance and achievement of the study aims.
- Previous malignancies in the preceding 3 years except for:
- In situ cancer of the uterine cervix
- Adequately treated basal cell skin carcinoma
- Adequately treated early stage non-pancreatic malignancy in complete remission for at least 3 years
- 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.
- Previous RT to upper abdomen
- Recurrent cancer following definitive pancreatic surgery
- Lymphoma or neuroendocrine tumours of the pancreas
- Known haemophilia A and B, chronic hepatitis type B or C.
- Other experimental treatment 6 weeks or less prior to registration into this study (including chemotherapy and immunotherapy).
- Known hypersensitivity to any of the IMPs or any of their excipients.
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
- Known galactose intolerance, Lapp-lactose deficiency or glucose-galactose malabsorption
- History of severe unexpected reaction to fluoropyrimidine therapies
- If the following concomitant medications cannot be discontinued temporarily during the CRT phase then the patients cannot enter the trial:
- Sorivudineand analogues e.g. brivudine
- Allopurinol and dipyridamole
- Known HIV positive disease (but routine screening for HIV is not required)
The objective of Stage 1 is 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.
Does increasing radiotherapy dose schedule from 50.4Gy (in 28 fractions) to 60Gy (in 30 fractions) improve the 12 month overall survival (OS) rate?
- Does the addition of nelfinavir to CRT improve the progression free survival (PFS) in LANPC?
Stage 2: Secondary objectives:
- To evaluate safety, overall survival and resection rates with the addition of nelfinavir to CRT
- To study the effect of increasing radiotherapy dose schedule on progression free survival and resection rates
- To evaluate safety and efficacy with the addition of CRT.
- To assess the resection rates and quality of life with the addition of CRT.
- To measure CA19-9 level, local control rate for each arm
- To assess the feasibility of RT planning protocol
- To determine objective disease response rate for each arm
Funding and Acknowledgements:
This work is supported by CRUK [grant number C28958/A17139 Application Title: CRUK/07/040: SCALOP-2]
Celgene are providing an educational grant and free nab-paclitaxel to support the study.
Radiotherapy Trials Quality Assurance provided by NCRI Radiotherapy Trials Quality Assurance Team (RTTQA)
Trial Management: Oncology Clinical Trials Office & Statistical Input: Centre for Statistics in Medicine both part of Oxford Clinical Trials Research Unit (OCTRU), a UKCRC and NCRI registered Clinical Trials.
SCALOP-2 Trial Office (OCTO)
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