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

Sponsor

University of Oxford (Other)

Overall Status

Unknown status

CT.gov ID

NCT02024009

Collaborator

Celgene (Industry), Cancer Research UK (Other)

289

Enrollment

Locations

Arms

Duration (Months)

26.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Anticipated 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 :

Mar 1, 2016

Anticipated Primary Completion Date :

Aug 1, 2020

Anticipated Study Completion Date :

Aug 1, 2020

Arms and Interventions

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 Names: Abraxane Radiation: 50.4Gy in 28# Drug: Nelfinavir VIRACEPT® (nelfinavir mesylate) is an inhibitor of the human immunodeficiency virus (HIV) protease. Other Names: 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 Names: 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 Names: 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 Names: 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 Names: Abraxane Radiation: 60Gy in 30# Drug: Nelfinavir VIRACEPT® (nelfinavir mesylate) is an inhibitor of the human immunodeficiency virus (HIV) protease. Other Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: GEMZAR

Outcome Measures

Primary Outcome Measures

Overall survival [12 months]
Progression free survival [12 months]

Secondary Outcome Measures

Toxicity [12 months]
Common Toxicity Criteria for Adverse Effects (CTCAE) v 4.02
Quality of life [12 months]
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ) - C30 and PAN26 for pancreatic cancer.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

1. 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)
WHO PS 0-1 (APPENDIX 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 - APPENDIX 3))
Written informed consent obtained
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.
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:

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.
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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oxford University Hospitals, Churchill Cancer Centre	Headington	Oxfordshire	United Kingdom	OX3 7LE
2	Bristol Haematoloy and Oncology Centre	Bristol		United Kingdom	BS2 8ED
3	Addenbrookes Hospital	Cambridge		United Kingdom	CB2 0QQ
4	Velindre Cancer Centre	Cardiff		United Kingdom	CF14 2TL
5	Castle Hill Hospital	Cottingham		United Kingdom	HU16 5JQ
6	University Hospital	Coventry		United Kingdom	CV2 2DX
7	Royal Surrey County Hospital	Guildford		United Kingdom	GU2 7XX
8	St James' Hospital	Leeds		United Kingdom
9	University College London Hospital	London		United Kingdom	NW1 2BU
10	Royal Free Hospital	London		United Kingdom	NW3 2PF
11	Hammersmith Hospital	London		United Kingdom	W12 0HS