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JOURNAL ONKOLOGIE – STUDIE
PHITT

Paediatric Hepatic International Tumour Trial

Rekrutierend

NCT-Nummer:
NCT03017326

Studienbeginn:
August 2017

Letztes Update:
09.09.2022

Wirkstoff:
Cisplatin, Doxorubicin, Carboplatin, 5Fluorouracil, Vincristine, Etoposide, Irinotecan, Gemcitabine, Oxaliplatin, Sorafenib

Indikation (Clinical Trials):
Carcinoma, Hepatocellular, Hepatoblastoma

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
Phase 3

Sponsor:
University of Birmingham

Collaborator:
Fundació Institut Germans Trias i Pujol, University Hospital Munich, University Hospital, Bonn, University of Kiel, University Hospital Tuebingen, University of Padova, Ludwig-Maximilians - University of Munich, Medical University of Gdansk, Cliniques universitai

Studienleiter

Madhumita Dandapani, MD PhD
Principal Investigator
University of Nottingham
Marc Ansari, MD
Principal Investigator
University of Geneva

Kontakt

Studienlocations
(3 von 31)

Ludwig-Maximillians-University Munich
80337 Munich Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Rebecca Maxwell
Phone: 015254889395
E-Mail: rebecca.maxwell@med-uni-muenchen.de» Ansprechpartner anzeigen
Royal Aberdeen Children's Hospital
AB25 2ZG Aberdeen
United KingdomRekrutierend» Google-Maps
Royal Belfast Hospital for Sick Children
BT12 6BE Belfast
United KingdomRekrutierend» Google-Maps
Birmingham Children's Hospital
B4 6NH Birmingham
United KingdomRekrutierend» Google-Maps
Bristol Royal Hospital for Children
BS2 8BJ Bristol
United KingdomRekrutierend» Google-Maps
Addenbrooke's Hospital
CB2 0QQ Cambridge
United KingdomRekrutierend» Google-Maps
Noah's Ark Children's Hospital for Wales
CF14 4XW Cardiff
United KingdomRekrutierend» Google-Maps
Royal Hospital for Children
EH9 1LW Edinburgh
United KingdomRekrutierend» Google-Maps
Royal Hospital for Children
G51 4TF Glasgow
United KingdomRekrutierend» Google-Maps
Leeds General Infirmary
LS1 3EX Leeds
United KingdomRekrutierend» Google-Maps
Leicester Royal Infirmary
LE1 5WW Leicester
United KingdomRekrutierend» Google-Maps
Alder Hey Children's Hospital
L12 2AP Liverpool
United KingdomRekrutierend» Google-Maps
Great Ormond Street Hospital
WC1N 3JH London
United KingdomRekrutierend» Google-Maps
Royal Manchester Children's Hospital
M13 9WL Manchester
United KingdomRekrutierend» Google-Maps
Great North Children's Hospital
NE1 4LP Newcastle Upon Tyne
United KingdomRekrutierend» Google-Maps
Nottingham Children's Hospital
NG7 2UH Nottingham
United KingdomRekrutierend» Google-Maps
Oxford Children's Hospital
OX3 9DU Oxford
United KingdomRekrutierend» Google-Maps
Sheffield Children's Hospital
S10 2TH Sheffield
United KingdomRekrutierend» Google-Maps
University Hospital Southampton
SO16 6YD Southampton
United KingdomRekrutierend» Google-Maps
The Royal Marsden Hospital
SM2 5PT Sutton
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

The trial will evaluate whether reducing treatment for low risk HB patients maintains their

excellent event free survival (EFS) and decreases acute and long-term toxicity.

Intensification of therapy with the use of novel agents will be evaluated in the high risk

group. The trial will also compare three different regimens in intermediate risk HB.

Patients with HCC will be divided into groups based on whether the tumour is resectable or

unresectable and/or metastatic.

Evaluation of the biology of HB and HCC, using the identification/validation of novel and

already reported prognostic biomarkers as well as toxicity biomarkers is a key strand of this

trial, so patients in all risk groups can be registered. The trial is also designed to

optimise the collection of clinically annotated biologic specimens and establish the world's

largest repository of blood and tissue samples from paediatric patients with HB and HCC.

The trial includes 4 randomised comparisons addressing therapeutic questions. For low risk HB

patients, outcome with a total of 4 cycles of treatment is not inferior to those receiving a

total of 6 cycles of treatment.

For intermediate risk patients, 3 regimens will be compared for outcome and toxicity.

For high risk patients, 2 post induction regimens will be compared for outcome. For resected

HCC patients, the addition of GEMOX to PLADO regimen will be compared.

In addition the following will be assessed:

- To validate a new global risk stratification, defined by Children's Hepatic Tumours

International Collaboration (CHIC)

- To evaluate clinically relevant factors, including the following:

- Provide a comprehensive and highly-validated panel of diagnostic and prognostic

biomarkers

- Determine if paediatric HCC is a biologically different entity to adult HCC

- Develop genomic and/or biomarker analysis to predict children who may have an

increased risk of developing toxicity with chemotherapy.

- To establish a collection of clinically and pathologically-annotated biological samples.

- Evaluate a surgical planning tool for an impact on decision making processes in

POST-TEXT III and IV HB

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Clinical diagnosis of HB* and histologically defined diagnosis of HB or HCC.

*Histological confirmation of HB is required except in emergency situations where:

- a) the patient meets all other eligibility criteria, but is too ill to undergo a

biopsy safely, the patient may be enrolled without a biopsy.

- b) there is anatomic or mechanical compromise of critical organ function by

tumour (e.g., respiratory distress/failure, abdominal compartment syndrome,

urinary obstruction, etc.)

- c) Uncorrectable coagulopathy

- Age ≤30 years

- Written informed consent for trial entry

Exclusion Criteria:

- Any previous chemotherapy or currently receiving anti-cancer agents

- Recurrent disease

- Previously received a solid organ transplant; other than orthotopic liver

transplantation (OLT).

- Uncontrolled infection

- Unable to follow or comply with the protocol for any reason

- Second malignancy

- Pregnant or breastfeeding women

Studien-Rationale

Primary outcome:

1. Event-free survival (EFS) (Time Frame - From date of randomisation (or registration into the trial for non-randomised patients), until date of first failure event, assessed up to 6 years.):
Event-free survival (EFS) is defined as the time from randomisation (or registration into the trial for non-randomised patients) to first failure event. Patients who have not had an event will be censored at their last follow-up date. Failure events are: progression of existing disease or occurrence of disease at new sites, death from any cause prior to disease progression, diagnosis of a second malignant neoplasm.

2. Response in HCC is defined as complete (CR) or partial (PR) response according to RECIST version 1.1 criteria (Time Frame - From date of screening assessment until date of first response assessment, up to 63 days in Group F):
Response in HCC is defined as complete (CR) or partial (PR) response according to RECIST version 1.1 criteria. The assessment will be performed after 3 cycles of PLADO, or 4 cycles of PLADO+S/GEMOX+S in Group F. Patients who are not assessable for response - e.g. because of early stopping of treatment or death - will be assumed to be non-responders.

Secondary outcome:

1. Failure-free survival (FFS) (Time Frame - From date of randomisation (or registration into the trial for non-randomised patients) until date of first failure event, or date of last follow up assessment, assessed up to 6 years.):
Failure-free survival (FFS) is defined as the time from randomisation (or registration into the trial for non-randomised patients) to first failure event. Patients who have not had an event will be censored at their last follow-up date. Failure events are: progression of existing disease or occurrence of disease at new sites, death from any cause prior to disease progression, diagnosis of a second malignant neoplasm. failure to go to resection.

2. Overall survival (OS) (Time Frame - From date of randomisation (or registration for non-randomised patients) until date of death from any cause, or date of last follow up assessment, assessed up to 6 years.):
Overall survival (OS) is defined as the time from randomisation (or registration for non-randomised patients) to death from any cause. Patients who have not died will be censored at their last follow-up date.

3. Toxicity categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE) (Time Frame - From date of start of randomised treatment until date 30 days after last treatment.):
Toxicity will be recorded in relation to each cycle of randomised treatment and will be categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE)

4. Chemotherapy-related cardiac, nephro- and oto-toxicity using Common Terminology Criteria for Adverse Events (CTCAE) (Time Frame - From date of start of randomised treatment until date 30 days after last treatment.):
Chemotherapy-related cardiac, nephro- and oto-toxicity will be recorded in relation to each cycle of treatment and will be categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE)

5. Hearing loss according to the SIOP Boston Scale (Time Frame - From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.):
Hearing loss will be measured according to the SIOP Boston Scale for oto-toxicity. The assessment will be performed at end of treatment (EOT) and follow up

6. Best Response (Time Frame - From date of first treatment until the date of last treatment, or until the date of first documented progression or date of death, assessed up to 6 months.):
Best Response is defined as CR or PR and is based on radiological response (RECIST v1.1) and Alpha Fetoprotein (AFP) decline. Best Response will be measured throughout treatment period. Patients who are not assessable for response - e.g. because of early stopping of treatment or death - will be assumed to be non-responders.

7. Surgical resectability defined as complete resection, partial resection or transplant (Time Frame - From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.):
Surgical resectability is defined as complete resection, partial resection or transplant

8. Adherence to surgical guidelines (Time Frame - From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years.):
Adherence to surgical guidelines is defined as the local clinician's surgical decision to resect or not compared to the current SIOPEL surgical guidelines.

Studien-Arme

  • Other: Group A Very Low Risk HB
    Patients with well differentiated foetal histology will receive 2 cycles of Cisplatin (2x 100mg/m2). Patients will non-well differentiated histology will be followed up only (no intervention).
  • Active Comparator: Group B Low Risk HB
    Patients who are resected after 2 cycles of Cisplatin will be randomised to receive 4 or 6 cycles of Cisplatin overall (80mg/m2). Patients who are not resected will continue to receive up to 6 cycles of Cisplatin (80mg/m2) until resection.
  • Active Comparator: Group C Intermediate Risk HB
    Patients will be randomised to receive Cisplatin (80mg/m2), Carboplatin (500mg/m2) and Doxorubicin (60mg/m2) as SIOPEL-3HR (5 cycles), Cisplatin (100mg/m2), Doxorubicin (60mg/m2) 5-Fluorouracil (600mg/m2) and Vincristine (4.5mg/m2) as C5VD (6 cycles), or 6 cycles of high dose Cisplatin (100mg/m2)
  • Active Comparator: Group D High Risk HB
    Patients will receive SIOPEL-4 regimen (Cisplatin 70mg/m2, Doxorubicin 30mg/m2) then have surgery. Post surgery, patients with remaining metastases will be randomised to receive 6 cycles of either Carboplatin (500mg/m2) and Doxorubicin (40mg/m2) alternating with Carboplatin (800mg/m2) and Etoposide (400mg/m2), or Carboplatin (500mg/m2) and Doxorubicin (40mg/m2) alternating with Vincristine (3mg/m2) and Irinotecan (250mg/m2). Patients with no metastases will receive the standard treatment of 3 cycles of Carboplatin (500mg/m2) and Doxorubicin (40mg/m2).
  • Other: Group E Resected HCC
    Patients with an underlying predisposition to HCC through genetic, viral or metabolic conditions will be followed up (no intervention). De novo or fibrolamellar HCC patients will receive 4 cycles of PLADO regimen (Cisplatin (80mg/m2) and Doxorubicin (60mg/m2)) over 4 cycles.
  • Active Comparator: Group F Unresected HCC
    Patients will be randomised to receive up to 6 cycles of PLADO (Cisplatin 80mg/m2, Doxorubicin 60mg/m2) with Sorafenib (300mg/m2) or up to 8 cycles of PLADO with Sorafenib and GEMOX (Gemcitabine 1000mg/m2, Oxaliplatin 100mg/m2) with Sorafenib (300mg/m2)

Geprüfte Regime

  • Cisplatin:
    Arms A and B - cisplatin is used alone Arms C, D, E and F - cisplatin us used in combination
  • Doxorubicin:
    Arms C, D and E used in combination
  • Carboplatin:
    Arms C and D used in combination
  • 5Fluorouracil:
    Arm C used alone
  • Vincristine:
    Arms C and D used in combination
  • Etoposide:
    Arm D used in combination
  • Irinotecan:
    Arm D used in combination
  • Gemcitabine:
    Arm F used in combination
  • Oxaliplatin:
    Arm F used in combination
  • Sorafenib:
    Arm used in combination

Quelle: ClinicalTrials.gov


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