Condition category
Cancer
Date applied
19/04/2017
Date assigned
24/04/2017
Last edited
14/05/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

www.birmingham.ac.uk/research/activity/mds/trials/crctu/trials/phitt

Contact information

Type

Public

Primary contact

Mr Steve Baker

ORCID ID

Contact details

PHITT Study Office
Cancer Research UK Clinical Trials Unit
Institute of Cancer and Genomic Sciences
The University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 121 415 1061
phitt@trials.bham.ac.uk

Additional identifiers

EudraCT number

2016-002828-85

ClinicalTrials.gov number

Protocol/serial number

33836

Study information

Scientific title

Paediatric Hepatic International Tumour Trial (PHITT)

Acronym

PHITT

Study hypothesis

This study aims to:
1. Reduce treatment for very low and low risk group patients, while maintaining the excellent event-free survival (EFS) in these groups to reduce side effects of treatment.
2. Intensify therapy in the high risk group to improve the surgery options available and the event free survival, while testing the use of new drugs in a clinical trial setting.
3. Compare different regimens to improve surgical options in intermediate risk HB
4. Evaluate the biology and genetics of HB and HCC to identify prognostic and toxicity biomarkers.

Ethics approval

West Midlands REC – Edgbaston, 10/04/2017, ref: 17/WM/0110

Study design

Randomised; Both; Design type: Treatment, Drug, Cross-sectional

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Children's Cancer and Leukaemia; UKCRC code/ Disease: Cancer/ Malignant neoplasms of digestive organs

Intervention

The patient will be approached with the option of joining the trial early in the diagnosis. The patient will be asked to confirm their consent to participate in the trial and for a sample of their tumour to be sent for research purposes. An assessment will be made to categorise the level of disease (called PRETEXT staging) using the age, AFP level, presence of metastases and tumour location. The level of disease will be categorised according to analysis by Children's Hepatic tumour International Collaboration (CHIC) - Hepatoblastoma Stratification. If appropriate, the patient will be asked to consent to receive treatment.

The patient will be allocated to one of six different treatment groups, depending on their disease:

Group A: Very Low Risk Hepatoblastoma (HB)
The results from the Central Pathology review of the patient's tumour tissue will be used to determine if the patient should receive cisplatin treatment or no treatment. If the tumour shows "WDF" histology, the patient receives no treatment and is seen at routine visits for follow up assessment only. If the tumour shows "non-WDF" histology, the patient receives a dose of cisplatin on Day 1 of two 21 day cycles.

Group B: Low Risk Hepatoblastoma
These patients will receive a dose of Cisplatin on Day 1 of two 14 day cycles.
The patient is then assessed for surgery to remove the tumour by the Consultant working on the study. If surgery is carried out, the patient is randomised to one of the following two arms:
1. Patient receives cycle 3 and cycle 4 of Cisplatin treatment or
2. Patient receives cycles 4-6 of Cisplatin treatment.
If surgery is not feasible after cycle 1 and cycle 2, the patient receives cycles 3 and 4 of Cisplatin treatment and is re-assessed for surgery. If surgery is still not feasible, the patient receives cycles 5 and 6 of Cisplatin treatment.

Group C: Intermediate Risk Hepatoblastoma
These patients will be randomised to receive one of the following three treatments.
1. SIOPEL3HR: A cardiology assessment to check the patient's heart function will be done prior to receiving treatment. Patients will receive Cisplatin on Day 1, Carboplatin on Day 15 and Doxorubicin on Days 15 & 16 in five 28 day cycles.
2. C5VD: A cardiology assessment will be done prior to receiving treatment. Patients will receive Cisplatin and Doxorubicin on Days 1 & 2; Doxorubicin, 5-Fluorouracil and Vincristine on Day 2; and Vincristine on Days 9 & 16. Each cycle of treatment is repeated after 21 days, and six cycles in total are given.
3. CDDP monotherapy: Patients will receive Cisplatin on Day 1 in six 14 day cycles.
Patients will have a CT/MRI scan after the 2nd and 4th cycles of treatment to assess their disease, and have their tumour removed by surgery at an appropriate point in the treatment, depending on the scan results and the decision by their doctor. Following surgery, patients will have further cycles of treatment, until all cycles have been given.

Group D: High Risk Hepatoblastoma
These patients will first undergo induction therapy before undergoing surgery and further treatment.
During induction treatment, patients will receive Cisplatin on Day 1, Cisplatin and Doxorubicin on Day 8, Doxorubicin on Day 9 and Cisplatin again on Day 15 in three 15 day cycles.
If disease metastases are present after receiving the induction treatment, the patient will be randomised to receive one of the two following treatments:
1. CD/CE: Patients will receive Carboplatin and Doxorubicin (CD) on Day 1, followed by another dose of Doxorubicin on Day 2. Each cycle is 21 days. The patient will receive Carboplatin and Etoposide (CE) on Days 1-4 of Cycle 2. Cycle 1 (CD) and Cycle 2 (CE) will alternate until a total of 6 cycles are given.
2. CD/VI: Patients will receive Carboplatin and Doxorubicin (CD) on Day 1, followed by another dose of Doxorubicin on Day 2. Each cycle is 21 days. The patient will receive Vincristine and Irinotecan (VI) on Day 1 of Cycle 2, followed by more doses of Irinotecan on Days 2-5 of Cycle 2. Cycle 1 (CD) and Cycle 2 (VI) will alternate until a total of 6 cycles are given.
If disease metastases are not present following the induction treatment and surgery, the patient receives Carboplatin and Doxorubicin (CD) as described above.

Group E: Resectable Hepatocellular Carcinoma (HCC)
The type of HCC tumour removed during surgery will determine if the patient should receive PLADO (Cisplatin & Doxorubicin) treatment or no treatment. If the tumour is deemed Fibrolamellar, the patient receives no treatment and is seen at routine visits for follow up assessment only. If the tumour is deemed de novo HCC, the patient should receive a dose of Cisplatin and Doxorubicin on Day 1, and Doxorubicin on Day 2 of four 21 day cycles.

Group F: Unresectable/metastatic Hepatocellular Carcinoma
These patients will be randomised to receive one of the following two treatments:
1. PLADO + Sorafenib: Patients will receive Cisplatin and Doxorubicin on Day 1, Doxorubicin on Day 2 (PLADO) and Sorafenib on Days 3-21 of three 21 day cycles.
2. PLADO + Sorafenib/GEMOX + Sorafenib: Patients will receive Cisplatin and Doxorubicin on Day 1, Doxorubicin on Day 2 (PLADO) and Sorafenib on Days 3-14. Each cycle is 14 days. The patient will receive Gemcitabine, Oxaliplatin and Sorafenib on Day 1, and Sorafenib on Days 2-14 of Cycle 2. Cycle 1 (PLADO+Sorafenib) and Cycle 2 (PLADO+Sorafenib/GEMOX) will alternate until a total of 4 cycles are given.

At the end of the treatment patients will be seen at routine visits once every 3 months for the next 2 years for follow up assessment, including a physical examination, a CT/MRI scan and a blood test for disease indicator Alphafetoprotein levels.

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measures

1. Event-free survival (EFS) is measured as the time from randomisation (or registration into the trial for non-randomised patients) to first failure event or last follow-up date
2. Response in HCC is measured using RECIST version 1.1 criteria, after 3 cycles of PLADO, or 4 cycles of PLADO+S/GEMOX+S in Group F
3. Best Response is measured using RECIST version 1.1 criteria and AFP decline at end of treatment for Groups A, B, C, D and E

Secondary outcome measures

1. Overall survival (OS) is measured as the time from randomisation (or registration for non-randomised patients) to death from any cause
2. Toxicity is measured using Common Terminology Criteria for Adverse Events (CTCAE), at the end of each cycle of treatment
3. Hearing loss is measured using SIOP Boston Scale for oto-toxicity at end of treatment and follow up
4. Surgical resectability is measured using surgical outcome during treatment after surgery
5. Adherence to surgical guidelines is measured using the current SIOPEL surgical guidelines and the local clinician’s surgical decision to resect after surgical assessment

Overall trial start date

01/01/2016

Overall trial end date

31/12/2022

Reason abandoned

Eligibility

Participant inclusion criteria

1. Clinical diagnosis of HB and histologically defined diagnosis of HB or HCC.
2. Aged 0-30 years
3. Written informed consent for trial entry

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

Planned Sample Size: 300; UK Sample Size: 80

Participant exclusion criteria

1. Any previous chemotherapy or currently receiving anti-cancer agents
2. Recurrent disease
3. Previously received a solid organ transplant
4. Uncontrolled infection
5. Unable to follow the protocol for any reason
6. Second malignancy
7. Pregnant or breastfeeding women

Recruitment start date

01/05/2017

Recruitment end date

30/07/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Aberdeen Royal Infirmary
Foresterhill
Aberdeen
AB25 2ZN
United Kingdom

Trial participating centre

Royal Belfast Hospital for Sick Children
180 Falls Road
Belfast
BT12 6BE
United Kingdom

Trial participating centre

Birmingham Children's Hospital
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom

Trial participating centre

Bristol Royal Hospital for Children
Uhbristol Education Centre
Bristol
BS2 8AE
United Kingdom

Trial participating centre

Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Our Lady's Children's Hospital
Crumlin
Dublin
Dublin 12
Ireland

Trial participating centre

Royal Hospital for Sick Children Edinburgh
9 Sciennes Road
Edinburgh
EH9 1LF
United Kingdom

Trial participating centre

Royal Hospital for Children
1345 Govan Road
Glasgow
G51 4TF
United Kingdom

Trial participating centre

Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Alder Hey Children's Hospital
Eaton Road
Liverpool
L12 2AP
United Kingdom

Trial participating centre

Great Ormond Street Hospital for Children
Great Ormond Street
London
WC1N 3JH
United Kingdom

Trial participating centre

Royal Manchester Childrens Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom

Trial participating centre

Nottingham City Hospital
City Hospital Campus
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

John Radcliffe Hospital
Headley Way
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Sheffield Children's Hospital
Western Bank
Sheffield
S10 2TH
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Royal Marsden Hospital Sutton
Downs Road
Sutton
SM2 5PT
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 121 4158011
s.jennings@bham.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

European Commission

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Results of this trial will be submitted for publication in peer reviewed journals.

IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/07/2023

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

14/05/2018: Internal review. 16/01/2018: Internal review. 16/10/2017: Internal review.