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Trial registered on ANZCTR


Registration number
ACTRN12619000288123
Ethics application status
Approved
Date submitted
24/01/2019
Date registered
26/02/2019
Date last updated
19/08/2019
Date data sharing statement initially provided
26/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Neoadjuvant Immune-Chemo-Radiotherapy in operable oEsophageal and gastro-oesophageal junction cancers with Carboplatin Paclitaxel Radiotherapy and Avelumab - a Trial assessing feasibility and preliminary Efficacy
Scientific title
Neoadjuvant Immune-Chemo-Radiotherapy in operable oEsophageal and gastro-oesophageal junction cancers with Carboplatin Paclitaxel Radiotherapy and Avelumab - a Trial assessing feasibility and preliminary Efficacy
Secondary ID [1] 297198 0
NIl
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Oesophageal cancer 311247 0
gastro-oesophageal junction cancer 311452 0
Condition category
Condition code
Cancer 309866 309866 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Addition of Avelumab to chemoradiotherapy prior to surgery.
Patients will receive 5 weeks of weekly carboplatin-paclitaxel-radiotherapy.
Avelumab will be given as intravenous infusion at the dose of 10mg/kg over 60 minutes in 250mL Sodium Chloride 0.9% every 2 weeks concurrently with chemoradiotherapy. A further two doses of 2 weekly Avelumab will then be given alone. Total of 5 cycles of Avelumab.
Intervention code [1] 313451 0
Treatment: Drugs
Comparator / control treatment
No Control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 318814 0
Assess safety of the chemo-radiotherapy- immunotherapy combination in patients with operable oesophageal and Gastroeosophageal Junction adenocarcinoma. Measured by looking at the rates of any grade 3 or 4 toxicities.
Some of the common adverse events seen using the interventions on this trial are fatigue, nausea, vomiting, rash, decrease in blood counts, diarrhoea, constipation, allergic reactions and immune related reactions (such as inflammation of tissues).
These will be assessed through physical examinations.
Timepoint [1] 318814 0
3 years post treatment.
Primary outcome [2] 318815 0
Assess efficacy in terms of pathological complete response (pCR) for the overall study.

This will be determined post surgery by the analysis of the specimen resected.
Timepoint [2] 318815 0
At time of surgery
Primary outcome [3] 318982 0
Assess feasibility of the chemo-RT- immunotherapy combination in patients with operable oesophageal and GOJ adenocarcinoma.
This will be measured through the treatment being delivered per protocol
Timepoint [3] 318982 0
3 years post treatment
Secondary outcome [1] 366132 0
To assess the safety and tolerability profile of neo-adjuvant CRT-Av in patients with potentially operable oesophageal and GOJ adenocarcinoma as per CTCAE version 4.
This will be an ongoing review of safety data and any dose limiting toxicities observed,
Timepoint [1] 366132 0
The first timepoint is 10 patients completing chemoradiotherapy and avelumab with or without surgery.
The second timepoint will be when a further 5 patients reached surgery.
A final analysis will occur when all data is received for all patients, expected to be 3 years post last patient undergoing surgery

Eligibility
Key inclusion criteria
1. Male/female patients aged 18 years or older
2. Histologically confirmed gastro-oesophageal junction or oesophageal adenocarcinoma. Oesophageal and gastroesophageal junction tumours should be TNM7 stage T1-3 and N0-N1, with no evidence of distant metastases (M0) where the MDT believes that an R0 resection can be achieved at the outset. T4 or N2 cancers are excluded as per the CROSS trial eligibility and due to the possible variable need to prolong pre-operative chemotherapy or alternate chemotherapy regimen in CRT to reduce margin involvement and improve resectability.
3. Absence of distant metastases on CT scan and PET scan and staging laparoscopy (where indicated) prior to study entry.
4. No prior therapy for oesophageal or GOJ adenocarcinoma
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any contraindication or known hypersensitivity reaction to any of the study drugs, or components of carboplatin or paclitaxel.
2. Known severe hypersensitivity reactions to monoclonal antibodies (Grade equal to or greater than 3 NCI CTCAE v4.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of partially controlled asthma).
3. Patients who have received immunotherapy for a previous malignancy.
4. Any previous malignancy, with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
5. Any other histology apart from adenocarcinoma are excluded
6. Any previous malignancy where patient has had less than or equal to 5 years of a disease free period. If patient has had greater than or equal to 5 years disease free period and where patient is deemed cured, patient may be eligible subject to Chief principle investigator decision.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA

Funding & Sponsors
Funding source category [1] 301749 0
Commercial sector/Industry
Name [1] 301749 0
Merck Serono
Address [1] 301749 0
Merck KGaA, Frankfurter Str. 250, 64293 Darmstadt, Germany
Country [1] 301749 0
Germany
Primary sponsor type
Government body
Name
Southern Adelaide Local Health Network Inc
Address
Flinders Medical Centre
Flinders Drive
Bedford Park
SA 5042
Country
Australia
Secondary sponsor category [1] 301495 0
None
Name [1] 301495 0
Address [1] 301495 0
Country [1] 301495 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302474 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 302474 0
CALHN Research Office
Level 3 Roma Mitchell House
136 North Terrace Adelaide SA 500
Ethics committee country [1] 302474 0
Australia
Date submitted for ethics approval [1] 302474 0
14/11/2018
Approval date [1] 302474 0
06/05/2019
Ethics approval number [1] 302474 0

Summary
Brief summary
This study aims to evaluate the safety and preliminary efficacy of a drug called Avelumab in combination with chemotherapy plus radiotherapy (CRT) in patients with resectable oesophageal/ gastro-oesophageal junction (GOJ) adenocarcinoma.
Who is it for?
You may be eligible to join this study if you are aged 18 years or more, and have a confirmed diagnosis of early or local gastro-oesophageal junction or oesophageal adenocarcinoma.

Study details
All participants in this study will receive the drug Avelumab in addition to chemoradiotherapy (CRT). Patients will receive 5 weeks of carboplatin-paclitaxel-Radiotherapy. Avelumab will be given as intravenous infusion at the dose of 10mg/kg over 60 minutes in 250mL Sodium Chloride 0.9% every 2 weeks concurrently with CRT and then for 2 more cycles (total 5 cycles of Avelumab; 3 concurrently and 2 cycles as single agent) pre surgery. Surgery will be carried out 6-8 weeks post completion of the CRT component.

After surgery patients will then be followed up every 3 months for 2 years then 6 monthly for one year. Standard of care imaging results will be collected as well as blood tests.

It is hoped that this research will show support for improved patient outcomes by using an immunotherapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90338 0
Dr Amitesh Roy
Address 90338 0
Flinders Medical Centre
Flinders Drive
Bedford Park
SA 5042
Country 90338 0
Australia
Phone 90338 0
+61 8 82048997
Fax 90338 0
Email 90338 0
amitesh.roy@sa.gov.au
Contact person for public queries
Name 90339 0
Miss Kelly Mead
Address 90339 0
Flinders Medical Centre
Flinders Drive
Bedford Park
SA 5042
Country 90339 0
Australia
Phone 90339 0
+61 8 8204 6151
Fax 90339 0
Email 90339 0
kelly.mead@sa.gov.au
Contact person for scientific queries
Name 90340 0
Miss Kelly Mead
Address 90340 0
Flinders Medical Centre
Flinders Drive
Bedford Park
SA 5042
Country 90340 0
Australia
Phone 90340 0
+61 8 8204 6151
Fax 90340 0
Email 90340 0
kelly.mead@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No part of Ethical submission
What supporting documents are/will be available?
No other documents available
Summary results
No Results