Systemic Therapy and Chemoradiation in Advanced Localised Pancreatic Cancer - 2

NCT02024009 | Completed Phase 1 DMC

• 1 other identifier: OCTO_063
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 23

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, initially to one of the four options, but as of 26Feb2020, to one of two options, as 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 aimed to find the right dose of nelfinavir to combine with CRT, requiring 27 participants of whom up to 18 will receive nelfinavir together with CRT. The Maximum Tolerated Dose of nelfinavir for Stage 2 has been established as 1250mg bd based on the data of 4 patients in the Stage 1, 1250mg cohort. 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 168 participants and allocate 96 to 1 of the 4 following treatment arms (As from 26Feb2020, randomisation will continue into one of two arms): Arm A: Nelfinavir together with CRT (arm A closed on 26Feb2020) Arm B: CRT (without nelfinavir) Arm C: Nelfinavir together with CRT (but using a higher than conventional dose of radiotherapy) (arm C closed on 26Feb2020) Arm D: CRT without nelfinavir (but using a higher than conventional dose of radiotherapy) Participants allocated to any of the two arms, following closure of Arms A \& C on 26Feb2020, will receive one further cycle of chemotherapy prior to starting chemoradiotherapy (without nelfinavir). This is to allow time for radiotherapy planning. Participants who are ineligible or refuse randomisation will be treated as per local standard but will remain in the study for follow up every 12 weeks. Their data will contribute to an Overall Survival (OS) analysis.

Conditions

Pancreatic Neoplasms (Locally Advanced Non-metastatic)

Keywords

chemoradiotherapy; nelfinavir; abraxane; gemcitabine; radiotherapy; capecitabine

Outcome Measures

Primary Outcomes (2)

• Progression free survival

  Concurrent biological question (± Nelfinavir): Progression Free Survival (PFS) (time from registration to event (progression or death if death occurred without progression). Patients who are not assessed to have disease progression and are not observed to die during the course of the trial will be censored at the last known progression free follow-up date).

  From date of registration until date of first documented progression or death ( if death occurred without progression), assessed up until last patient last visit (43 months).

• Overall survival in LANPC

  RT dose question (50.4Gy v 60Gy): Overall survival (OS) (time from registration to event (death by any cause); patients who are not observed to die during the course of the trial will be censored at the last known date alive prior to end of trial date)

  From date of registration until date of first documented (death by any cause), assessed up until Last Patient Last Visit (43 months)

Secondary Outcomes (12)

• Concurrent biological question: Toxicity (Serious Adverse Events scored by using NCI CTCAE v4.03),

  12 months from date of registration

• Concurrent biological question: treatment compliance measured using patient diary cards

  12 months from date of registration

• Concurrent biological question: overall survival

  12 months from date of registration

• Concurrent biological question: resection rates

  12 months from date of registration

• RT dose question: PFS

  12 months from date of registration

Study Arms (4)

Arm A

EXPERIMENTAL

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# (arm A closed on 26Feb2020 due to lack of efficacy of nelfinavir) \*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; Radiation: 50.4Gy in 28#; Drug: Nelfinavir; Drug: Capecitabine; Drug: Gemcitabine

Arm B

EXPERIMENTAL

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; Radiation: 50.4Gy in 28#; Drug: Capecitabine; Drug: Gemcitabine

Arm C

EXPERIMENTAL

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# (arm C closed on 26Feb2020 due to lack of efficacy of nelfinavir) \*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; Radiation: 60Gy in 30#; Drug: Nelfinavir; Drug: Gemcitabine

Arm D

EXPERIMENTAL

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; Radiation: 60Gy in 30#; Drug: Gemcitabine

Interventions

nab-paclitaxel DRUG

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

Also known as: Abraxane

Arm A; Arm B; Arm C; Arm D

60Gy in 30# RADIATION

Arm C; Arm D

50.4Gy in 28# RADIATION

Arm A; Arm B

Nelfinavir DRUG

VIRACEPT® (nelfinavir mesylate) is an inhibitor of the human immunodeficiency virus (HIV) protease.

Also known as: Viracept

Arm A; Arm C

Capecitabine DRUG

Given in combination with gemcitabine, known as GemCap.

Arm A; Arm B

Gemcitabine DRUG

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

Also known as: GEMZAR

Arm A; Arm B; Arm C; Arm D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Aged 18 years or over
• Histologically or cytologically proven carcinoma of the pancreas
• Locally advanced, non-metastatic inoperable disease as per NCCN criteria (APPENDIX 2). 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)
• World Health Organisation PS 0-1 (APPENDIX 1)
• Adequate haematological function: neutrophils ≥1.5 x 109/L, platelets ≥100 x 109/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 ≥ 40ml/min (Cockcroft \& Gault - APPENDIX 3))
• Written informed consent obtained
• Women of child-bearing potential (APPENDIX 6) 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 6 months after last administration of GEMABX and to use an acceptable contraception method during chemoradiotherapy and for 6 months after completion of all treatment. (For a definition of highly effective and acceptable contraceptive methods see section 10.8)
• 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.

You may not qualify if:

• 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 chemothera¬py and immunotherapy).
• Known hypersensitivity to any of the IMPs or any of their excipients.

Sponsors & Collaborators

• University of Oxford: lead
• Celgene: collaborator
• Cancer Research UK: collaborator

Study Sites (23)

Oxford University Hospitals, Churchill Cancer Centre

Headington, Oxfordshire, OX3 7LE, United Kingdom

Location

NHS Grampian, Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, CH63 4JY, United Kingdom

Location

Belfast Health and Social Care Trust, Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

University Hospitals Bristol NHS Foundation Trust, Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Velindre NHS Trust, Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

East Suffolk and North Essex NHS Foundation Trust, Colchester District General Hospital

Colchester, CO4 5JL, United Kingdom

Location

Hull and East Yorkshire Hospitals NHS Trust, Castle Hill Hospital

Cottingham, HU16 5JQ, United Kingdom

Location

University Hospitals Coventry and Warwickshire NHS Trust, University Hospital Coventry

Coventry, CV2 2DX, United Kingdom

Location

Royal Surrey County Hospital

Guildford, GU2 7XX, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust, St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

United Lincolnshire Hospitals NHS Trust, Lincoln County Hospital

Lincoln, LN2 5QY, United Kingdom

Location

North Middlesex University Hospital NHS Trust, North Middlesex Hospital

London, N18 1QX, United Kingdom

Location

University College London Hospitals NHS Foundation Trust, University College London Hospital

London, NW1 2PG, United Kingdom

Location

Royal Free Hampstead NHS Trust, Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

The Christie NHS Foundation Trust, The Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Milton Keynes University Hospital

Milton Keynes, MK6 5LD, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, NR4 7UY, United Kingdom

Location

Nottingham University Hospitals NHS Trust, City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Plymouth Hospitals NHS Trust, Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Sheffield Teaching Hospitals, Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

Location

Related Publications (1)

• Strauss VY, Shaw R, Virdee PS, Hurt CN, Ward E, Tranter B, Patel N, Bridgewater J, Parsons P, Radhakrishna G, O'Neill E, Sebag-Montefiore D, Hawkins M, Corrie PG, Maughan T, Mukherjee S. Study protocol: a multi-centre randomised study of induction chemotherapy followed by capecitabine +/- nelfinavir with high- or standard-dose radiotherapy for locally advanced pancreatic cancer (SCALOP-2). BMC Cancer. 2019 Feb 4;19(1):121. doi: 10.1186/s12885-019-5307-z.

  PMID: 30717707 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Nelfinavir; Capecitabine; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Somnath Mukherjee, MD, FRCP, FRCR

  somnath.mukherjee@oncology.ox.ac.uk

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2013
• First Posted: December 31, 2013
• Study Start: March 1, 2016
• Primary Completion: June 23, 2021
• Study Completion: June 23, 2021
• Last Updated: July 25, 2024

Record last verified: 2021-07

Locations

GB (23)