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Systemic Therapy and Chemoradiation in Advanced Localised Pancreatic Cancer - 2 (SCALOP-2)

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ClinicalTrials.gov Identifier: NCT02024009
Recruitment Status : Recruiting
First Posted : December 31, 2013
Last Update Posted : October 16, 2018
Sponsor:
Collaborators:
Celgene
Cancer Research UK
Information provided by (Responsible Party):
University of Oxford

Brief Summary:

This study will evaluate the role of increasing radiotherapy dose and addition of nelfinavir to chemoradiotherapy (CRT) in patients with inoperable pancreatic cancer that has not spread beyond the pancreas.

Currently in the United Kingdom (UK), either chemotherapy alone or chemotherapy followed by CRT can be used in the management of inoperable pancreatic cancer that has not spread. CRT consists of 25-30 radiotherapy treatments in combination with chemotherapy. Although this treatment is effective in controlling local symptoms and slowing down the pace of cancer, in most cases it is unable to shrink it enough to make it operable. Some of the reasons for this could be the lack of oxygen and lack of blood flow within the tumour making it resistant to the effects of CRT. This study will investigate whether increasing the dose of radiotherapy, or increasing the oxygen and blood supply to the tumour by giving nelfinavir, or a combination of both, can improve outcomes. We also want to know what the additional toxicities from such intensive approaches are.

All participants will initially receive 12 weeks of chemotherapy, and those with stable or responding disease will receive further study treatment. The treatment allocation to 1 of the 5 options outlined below will be done at random by computer and neither the doctor nor the patient can choose the treatment option. The process of randomisation ensures that all treatment arms are equally balanced in terms of patient and tumour characteristics, and to reduce the possibility of bias.

The study will consist of 2 stages. In the 1st stage we aim to find the right dose of nelfinavir to combine with CRT, and this will require around 27 participants of whom up to 18 will receive nelfinavir together with CRT. In the 2nd stage, we want to find out the benefits of this approach over and above standard treatments and therefore we will recruit the order of 262 participants and allocate 170 to 1 of the 5 following treatment arms:

Arm A: Nelfinavir together with CRT Arm B: CRT (without nelfinavir) Arm C: Nelfinavir together with CRT (but using a higher than conventional dose of radiotherapy) Arm D: CRT without nelfinavir (but using a higher than conventional dose of radiotherapy) Arm E: Chemotherapy alone (without radiotherapy) Participants who are ineligible or refuse randomisation will be treated as per local standard but will remain in the study for follow up at 26, 39 and 52 weeks. Their data will contribute to an Overall Survival (OS) analysis.


Condition or disease Intervention/treatment Phase
Pancreatic Neoplasms (Locally Advanced Non-metastatic) Drug: nab-paclitaxel Radiation: 60Gy in 30# Radiation: 50.4Gy in 28# Drug: Nelfinavir Drug: Capecitabine Drug: Gemcitabine Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 289 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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 Start Date : March 2016
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A

12 weeks (3 cycles) of induction Gemcitabine and Nab-paclitaxel (GEMABX) chemotherapy then 1 cycle of GEMABX* whilst radiotherapy (RT) planned then capecitabine (830mg/m2 oral bd) + Nelfinavir** + 50.4 Grays (Gy) in 28#

*1 cycle GEMABX = 28 day cycle of intravenous Abraxane 125mg/m2 followed by gemcitabine 1000mg/m2 on day 1, 8 and 15.

Drug: nab-paclitaxel
Abraxane is a proprietary solvent-free, protein-stabilized formulation of paclitaxel comprised of paclitaxel and human albumin in a noncrystalline amorphous state
Other Name: Abraxane

Radiation: 50.4Gy in 28#
Drug: Nelfinavir
VIRACEPT® (nelfinavir mesylate) is an inhibitor of the human immunodeficiency virus (HIV) protease.
Other Name: Viracept

Drug: Capecitabine
Given in combination with gemcitabine, known as GemCap.

Drug: Gemcitabine
Gemcitabine is indicated for treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas. It is administered as an infusion
Other Name: GEMZAR

Experimental: Arm B

12 weeks (3 cycles) of induction GEMABX chemotherapy then 1 cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + 50.4Gy in 28#

*1 cycle GEMABX = 28 day cycle of intravenous Abraxane 125mg/m2 followed by gemcitabine 1000mg/m2 on day 1, 8 and 15.

Drug: nab-paclitaxel
Abraxane is a proprietary solvent-free, protein-stabilized formulation of paclitaxel comprised of paclitaxel and human albumin in a noncrystalline amorphous state
Other Name: Abraxane

Radiation: 50.4Gy in 28#
Drug: Capecitabine
Given in combination with gemcitabine, known as GemCap.

Drug: Gemcitabine
Gemcitabine is indicated for treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas. It is administered as an infusion
Other Name: GEMZAR

Experimental: Arm C

12 weeks (3 cycles) of induction GEMABX chemotherapy then

1 cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + Nelfinavir** + 60Gy in 30#

*1 cycle GEMABX = 28 day cycle of intravenous Abraxane 125mg/m2 followed by gemcitabine 1000mg/m2 on day 1, 8 and 15

Drug: nab-paclitaxel
Abraxane is a proprietary solvent-free, protein-stabilized formulation of paclitaxel comprised of paclitaxel and human albumin in a noncrystalline amorphous state
Other Name: Abraxane

Radiation: 60Gy in 30#
Drug: Nelfinavir
VIRACEPT® (nelfinavir mesylate) is an inhibitor of the human immunodeficiency virus (HIV) protease.
Other Name: Viracept

Drug: Gemcitabine
Gemcitabine is indicated for treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas. It is administered as an infusion
Other Name: GEMZAR

Experimental: Arm D

12 weeks (3 cycles) of induction GEMABX chemotherapy then

1 cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + 60Gy in 30#

*1 cycle GEMABX = 28 day cycle of intravenous Abraxane 125mg/m2 followed by gemcitabine 1000mg/m2 on day 1, 8 and 15.

Drug: nab-paclitaxel
Abraxane is a proprietary solvent-free, protein-stabilized formulation of paclitaxel comprised of paclitaxel and human albumin in a noncrystalline amorphous state
Other Name: Abraxane

Radiation: 60Gy in 30#
Drug: Gemcitabine
Gemcitabine is indicated for treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas. It is administered as an infusion
Other Name: GEMZAR

Experimental: Arm E

6 cycles of GEMABX*

*1 cycle GEMABX = 28 day cycle of intravenous Abraxane 125mg/m2 followed by gemcitabine 1000mg/m2 on day 1, 8 and 15.

Drug: nab-paclitaxel
Abraxane is a proprietary solvent-free, protein-stabilized formulation of paclitaxel comprised of paclitaxel and human albumin in a noncrystalline amorphous state
Other Name: Abraxane

Drug: Gemcitabine
Gemcitabine is indicated for treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas. It is administered as an infusion
Other Name: GEMZAR




Primary Outcome Measures :
  1. Overall survival [ Time Frame: 12 months ]
  2. Progression free survival [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Toxicity [ Time Frame: 12 months ]
    Common Toxicity Criteria for Adverse Effects (CTCAE) v 4.02

  2. Quality of life [ Time Frame: 12 months ]
    European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ) - C30 and PAN26 for pancreatic cancer.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. 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 (APPENDIX 2). The following types of interventions are allowed:

    1. Palliative bypass procedure
    2. Common bile duct stenting
  4. Primary pancreatic lesion 6 cm or less in diameter (taken from scan results)
  5. WHO PS 0-1 (APPENDIX 1)
  6. Adequate haematological function: neutrophils ≥1.5 x 109/L, platelets ≥100 x 109/L and haemoglobin ≥100g/L
  7. Adequate liver function tests:

    1. 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.
    2. AST and/or ALT ≤ 3 x ULN.
  8. Adequate renal function (GFR ≥ 50ml/min (Cockcroft & Gault - APPENDIX 3))
  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.

Exclusion criteria:

  1. Primary resectable cancer of the pancreas.
  2. Distant metastases
  3. Pregnant or breast-feeding 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 co-morbidities 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:

    1. In situ cancer of the uterine cervix
    2. Adequately treated basal cell skin carcinoma
    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 chemothera¬py 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, Lapp-lactose deficiency or glucose-galactose 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:

    1. Sorivudine and analogues e.g. brivudine
    2. Methotrexate.
    3. Allopurinol and dipyridamole
  17. Known HIV positive disease (but routine screening for HIV is not required)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02024009


Contacts
Contact: Rachel Shaw 01865 617078 octo-scalop-2@oncology.ox.ac.uk

Locations
United Kingdom
Oxford University Hospitals, Churchill Cancer Centre Recruiting
Headington, Oxfordshire, United Kingdom, OX3 7LE
Principal Investigator: Dr Somnath Mukherjee         
Bristol Haematoloy and Oncology Centre Recruiting
Bristol, United Kingdom, BS2 8ED
Principal Investigator: Dr Stephen Falk         
Addenbrookes Hospital Recruiting
Cambridge, United Kingdom, CB2 0QQ
Principal Investigator: Dr Thankamma Ajithkumar         
Velindre Cancer Centre Recruiting
Cardiff, United Kingdom, CF14 2TL
Principal Investigator: Dr Seema Arif, Dr         
Castle Hill Hospital Recruiting
Cottingham, United Kingdom, HU16 5JQ
Principal Investigator: Dr Rajarshi Roy         
University Hospital Recruiting
Coventry, United Kingdom, CV2 2DX
Principal Investigator: Dr Martin Scott-Brown         
Royal Surrey County Hospital Recruiting
Guildford, United Kingdom, GU2 7XX
Principal Investigator: Dr Sebastian Cummins         
St James' Hospital Recruiting
Leeds, United Kingdom
Principal Investigator: Dr Ganesh Radhakrishna         
University College London Hospital Not yet recruiting
London, United Kingdom, NW1 2BU
Principal Investigator: Dr John Bridgewater         
Royal Free Hospital Recruiting
London, United Kingdom, NW3 2PF
Principal Investigator: Dr Roopinder Gillmore         
Hammersmith Hospital Not yet recruiting
London, United Kingdom, W12 0HS
Principal Investigator: Dr Harpreet Wasan         
Sponsors and Collaborators
University of Oxford
Celgene
Cancer Research UK
Investigators
Principal Investigator: Somnath Mukherjee, MD, FRCP, FRCR somnath.mukherjee@oncology.ox.ac.uk

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT02024009     History of Changes
Other Study ID Numbers: OCTO_063
First Posted: December 31, 2013    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018

Keywords provided by University of Oxford:
chemoradiotherapy
nelfinavir
abraxane
gemcitabine
radiotherapy
capecitabine

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Gemcitabine
Albumin-Bound Paclitaxel
Capecitabine
Nelfinavir
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents