Cancer Research in HKUMed
12.Paediatric

12.0 Paediatric

12.1 Clinical Trial

12.1.1.1 Central Nervous System (Neuroblastoma)

Specific Selection Criteria: MYCN amplification

Second-line treatment: Phase 2

Immunotherapy (Anti- Gd2 IGG3 Antibody)

Study Title

Main Inclusion/Exclusion

Investigational Product

Principal Investigator

Department

Email

Contact number

A Pivotal Phase 2 Trial of Antibody naxitamab (hu3F8) and Granulocyte-Macrophage Colony Stimulating Factor (GM- CSF) in High-Risk Neuroblastoma Patients with Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow.

Key Inclusion criteria:

1. Documented diagnosis of NB as defined per INRC as:

    

    

   Or

    

   derived (MYCN) amplification, or c. MIBG-avid lesion(s).

    

2. High-risk NB patients with either primary refractory disease or incomplete response to salvage treatment (in both cases including SD, MR and PR) evaluable in bone and/or BM as defined in section 6.7. If disease is only present in bone the patient must have evaluable disease outside the radiation areas for being eligible in the trial, please see section 7.2.1. If disease is only present in the BM the involvement must be >5%.

• Histopathology of tumor biopsy,

• BM aspirate or biopsy indicative of NB by histology, plus high blood or urine catecholamine metabolite levels or Myelocytomatosis Viral-Related Oncogene, Neuroblastoma

Key Exclusion criteria:

1. Any systemic anti-cancer therapy, including chemotherapy or immunotherapy, within 3 weeks of 1st dose of GM-CSF.

    

2. Evaluable NB outside bone and BM defined as follows:

    

• MIBG-avid tumor: Definite MIBG uptake in tumor tissues outside bone and BM.

   

• MIBG nonavid tumor: Definite uptake in tumor tissues outside bone and BM on FDG-PET.

   

1. Actively progressing disease at trial entry according to Park criteria (Park et al. 2017).

Naxitamab (Anti- Gd2 IGG3 Monoclonal Antibody)

Professor Godfrey Chi-Fung Chan

Department of Paediatrics & Adolescent Medicine

gcfchan@hku.hk

2255 4481

12.1.1.2 Central Nervous System (Neuroblastoma)

Specific Selection Criteria: MYCN amplification

Second-line treatment: Phase 2

Immunotherapy (Anti- Gd2 IGG3 Antibody), Granulocyte-Macrophage Colony Stimulating Factor, Chemotherapy

An International, Single-Arm, Multicenter Phase 2 Trial. Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor in Combination with Irinotecan and temozolomide in Patients with High-Risk Neuroblastoma with Primary Refractory Disease or in First Relapse.

Key Inclusion criteria:

1. Documented neuroblastoma at time of initial diagnosis defined as:

    

    

2. Documented high-risk disease at time of initial diagnosis defined as:

    

    

    

3. Patient should have received standard of care frontline induction/ consolidation therapy (surgery, chemotherapy, autologous stem cell transplant, MIBG, radiotherapy, immunotherapy, or retinoids).

    

4. Patients must have active disease despite previous aggressive multi-drug chemotherapy (≥ 2 agents, including an alkylating agent and a platinum containing compound) defined as one of the following:

• Histopathological verification of neuroblastoma or ganglioneuroblastoma nodular, or Bone Marrow aspirate or biopsy indicative of neuroblastoma (according to International Neuroblastoma Response Criteria and high blood or urine catecholamine metabolite levels (> 2 x upper limit of normal).

• MYCN-amplified any stage (according to International Neuroblastoma Risk Group) of any age,.

   

  Or

• MYCN-nonamplified with stage M (according to International Neuroblastoma Risk Group) and diagnosed at ≥18 months of age or MYCN-nonamplified with INRG stage L2, diagnosed at ≥ 18 months and with unfavorable histology.

   

• MYCN-nonamplified INRG stage M, diagnosed at 12 to < 18 months and with unfavorable histology or DNA index=1.

• Verified first progression during multi-drug frontline treatment.

   

  Or

   

• Verified first episode of relapse, defined as recurrence after response to frontline treatment.

   

  Or

   

• Verified first designation of refractory disease, defined as persistent metastatic disease (SD or minor response by International Neuroblastoma Response Criteria and MIBG curie score ≥3) detected at conclusion of at least 4 cycles of multi-drug induction chemotherapy on or according to a high-risk NB treatment protocol.

Key Exclusion criteria:

1. Any systemic anti-cancer therapy, including chemotherapy, or immunotherapy, within 3 weeks prior to enrollment.

    

2. Autologous Stem Cell Transplantation or stem cell infusion within 6 weeks prior to enrollment.

    

3. Therapeutic 131I-MIBG within 6 weeks prior to enrollment.

    

4. Radiation therapy within 4 weeks prior to enrollment at the site of any lesion that will be identified as a target lesion to measure tumor response. Lesions that have been previously radiated cannot be used as target lesions unless there is radiographic evidence of progression at the site following radiation or a biopsy done following radiation shows viable neuroblastoma. There are no time restrictions following prior radio therapy for non-target lesions or for palliative radiation to sites that will not be used for response assessment.

    

5. Prior treatment with anti-GD2 therapy if the patient experienced progressive disease while on anti-GD2 treatment.

Naxitamab (Anti- Gd2 IGG3 Monoclonal Antibody) + Granulocyte-Macrophage Colony Stimulating Factor

+ Irinotecan (Chemo/ Topoisomerase I inhibitors) + temozolomide (Chemo)

Professor Godfrey Chi-Fung Chan

Department of Paediatrics & Adolescent Medicine

gcfchan@hku.hk

2255 4481

12.1 Clinical Trial

12.1.3 Bone: Osteosarcoma

Second-line or Third-line treatment: Phase 2

Targeted Therapy (Multiple Kinase Inhibitor), Chemotherapy

Study Title

Main Inclusion/Exclusion

Investigational Product

Principal Investigator

Department

Email

Contact number

A Multicenter, Open-label, Randomized Phase 2 Study to Compare the Efficacy and Safety of Lenvatinib in Combination With Ifosfamide and Etoposide Versus Ifosfamide and Etoposide in Children, Adolescents and Young Adults With Relapsed or Refractory Osteosarcoma (OLIE).

Key Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of high-grade osteosarcoma.

    

2. Refractory or relapsed osteosarcoma after 1 to 2 prior lines of systemic treatments.

    

3. Measurable or evaluable disease per RECIST 1.1 that meets the following criteria:

    

   • Measurable disease is defined as a lesion with a minimum size (by long axis) of 10 mm using computed tomography/magnetic resonance imaging (CT/MRI) (lymph nodes must be accurately measurable with a minimum size [by short axis] of 15 mm).

      

   • Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must have subsequently grown unequivocally to be deemed a target lesion.

    

   • Any other non-measurable lesions will be considered evaluable disease.

    

4. Aged 2 years to ≤25 years at the time of informed consent.

    

5. Life expectancy of 12 weeks or more.

Key Exclusion Criteria:

1. Any active infection or infectious illness unless fully recovered prior to Cycle 1 Day 1 (i.e., no longer requiring systemic treatment).

    

2. Subjects with central nervous system metastases are not eligible, unless they have completed local therapy (e.g., whole brain radiation therapy, surgery, or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 2 weeks before Cycle 1 Day 1.

    

3. Active second malignancy within 2 years prior to enrollment ([in addition to osteosarcoma], but not including definitively treated superficial melanoma, carcinoma-in-situ, basal or squamous cell carcinoma of the skin).

    

4. Any medical or other condition that in the opinion of the investigator(s) would preclude the subject’s participation in a clinical study.

    

5. Has had major surgery within 3 weeks prior to Cycle 1 Day 1. Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility

Lenvatinib (Multiple Kinase Inhibitor) + ifosfamide and etoposide

Vs.

Ifosfamide and etoposide

Professor Godfrey Chi-Fung Chan

Department of Paediatrics & Adolescent Medicine

gcfchan@hku.hk

Professor Godfrey Chi-Fung Chan

2255 4481

12.1 Clinical Trial

12.1.4 Haematology (Lymphoblastic lymphoma)

First-line treatment: Phase 3

Chemotherapy

Study Title

Main Inclusion/Exclusion

Investigational Product

Principal Investigator

Department

Email

Contact number

A Phase 3 trial, International cooperative treatment protocol for children and adolescents with lymphoblastic lymphoma.

Key Inclusion Criteria:

1. Children and adolescents under 18 year of age with a newly diagnosed lymphoblastic lymphoma.

    

2. Willingness of patients and the investigator/pathologist to provide adequate slides/blocks for reference (molecular) pathology and international pathology panel and/or fresh or fresh frozen samples for genetic risk group stratification if these samples are available after standard diagnostic procedures.

Key Exclusion criteria:

1. Lymphoblastic lymphoma as secondary malignancy.

Multiple treatment agents: Cyclophosphamide,

Cytarabine,

Dexamethasone,

Daunorubicin,

Doxorubicin,

Ifosfamide,

6-Mercaptopurine,

Methotrexate,

PEG asparaginase,

Prednisone,

Prednisolone,

Thioguanine,

Vincristine,

Vindesine.

Dr Alan Kwok-shing Chiang

Department of Paediatrics & Adolescent Medicine

chiangak@hku.hk

2255 4482

12.1 Clinical Trial

12.1.5 Hepatobiliary (Hepatic Malignancies)

First-line treatment: Phase 3

Chemotherapy

Study Title

Main Inclusion/Exclusion

Investigational Product

Principal Investigator

Department

Email

Contact number

A Phase 3 trial, Pediatric Hepatic Tumor International Therapeutic Trial (PHITT).

Key Inclusion Criteria:

1. Patients must be newly diagnosed with histologically-proven primary pediatric hepatic malignancies including hepatoblastoma or hepatocellular carcinoma.

    

2. Patients may have had surgical resection of the hepatic malignancy prior to enrollment.

Key Exclusion Criteria:

1. Prior chemotherapy.

    

2. Performance status below 50%.

    

3. Renal failure.

Multiple treatment agents:

Carboplatin,

Cisplatin,

Doxorubicin,

Etoposide,

Fluorouracil,

Gemcitabine,

Irinotecan,

Oxaliplatin,

Sorafenib,

Vincristine Sulfate.

Dr Alan Kwok-shing Chiang

Department of Paediatrics & Adolescent Medicine

chiangak@hku.hk

2255 4482

12.1 Clinical Trial

12.1.6 Tumour-Agnostic

Advanced or Metastatic, Unresectable

Specific Selection Criteria: Multiple Oncogenic Genomic Alterations

First-line or Second-line treatment: Phase 2

Immunotherapy / Targeted Therapy

Study Title

Main Inclusion/Exclusion

Investigational Product

Principal Investigator

Department

Email

Contact number

Tumor-Agnostic Precision Immuno-Oncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial

Key Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of advanced and unresectable or metastatic solid malignancy.

    

2. Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment.

Key Exclusion Criteria:

1. Patients who meet any of the following criteria will be ineligible for NGS biomarker eligibility testing (if required) and excluded from study entry in any cohort:

    

   • Current participation or enrollment in another therapeutic clinical trial.

    

   • Any anti-cancer treatment within 2 weeks or 5 half-lives (whichever is longer) prior to start of study treatment.

    

   • Whole brain radiotherapy within 14 days prior to start of study treatment.

    

   • Stereotactic radiosurgery within 7 days prior to start of study treatment.

    

   • Pregnant or breastfeeding, or intending to become pregnant during the study.

      

2. History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study.

Entrectinib,

Alectinib,

Atezolizumab,

Ipatasertib,

Trastuzumab emtansine,

Idasanutlin,

Inavolisib,

Belvarafenib,

Pralsetinib,

GDC-6036,

Camonsertib.

Professor Godfrey Chi-Fung Chan

Department of Paediatrics & Adolescent Medicine

gcfchan@hku.hk

2255 4481

12.0 Paediatric

12.2 Supportive Cancer Care

Study Title

Main Inclusion/Exclusion

Principal Investigator

Department

Email

Contact number

Individualized Neurofeedback treatment for paediatric brain tumour survivors with attentional deficits, a randomized-controlled trial (RCT)

Key Inclusion Criteria:

1. Previously diagnosed with Paediatric Brain Tumour with history of cranial irradiation.

    

2. Age between 3 to 18.

Key Exclusion Criteria:

1. Diagnosis of cerebral palsy/ history of structural brain abnormalities on CT/ MRI or grade III or IV IVH on either side of the brain; genetic/ syndromic disorders.

    

2. A history of seizure or prior electroencephalogram abnormalities related to epilepsy, the use of any psychotropic medications before the study.

Dr. Winnie Wan-Yee Tso

Department of Paediatrics & Adolescent Medicine

wytso@hku.hk

2255 4269

12.0 Paediatric

12.3.1 Translational Research

Study Title

Principal Investigator

Department

Email

Contact number

HMRF - Longitudinal analysis of Epstein-Barr virus-specific T cells and NK cell responses in paediatric patients with infectious mononucleosis and post-transplant lymphoproliferative disorder - Laboratory research study on longitudinal patients' blood and plasma samples

Dr Alan Kwok-shing Chiang

Department of Paediatrics & Adolescent Medicine

chiangak@hku.hk

2255 4482

12.3.2 Translational Research

HMRF - Analysis of Epstein-Barr virus (EBV) genomic variations in EBV-associated lymphoproliferative diseases - Laboratory research study on next generation sequencing of viral genomes harbored in blood, saliva and plasma samples of patients

Dr Alan Kwok-shing Chiang

Department of Paediatrics & Adolescent Medicine

chiangak@hku.hk

2255 4482

12.3.3 Translational Research

HMRF - Characterisation of pathogenetic mechanisms of Epstein-Barr virus-associated T and natural killer cell lymphoproliferative diseases in children - Laboratory research study on immunology and genomics of patients' blood and plasma samples

Dr Alan Kwok-shing Chiang

Department of Paediatrics & Adolescent Medicine

chiangak@hku.hk

2255 4482

12.0 Paediatric

12.4.1 Basic Research (Brain Tumor)

Study Title

Main Inclusion/Exclusion

Principal Investigator

Department

Email

Contact number

Exploring Neuro-electrophysiological Markers of Neurocognitive Outcomes in Paediatric Brain Tumour Survivors

Key Inclusion Criteria:

1. Previously diagnosed with Paediatric Brain Tumour with history of cranial irradiation.

    

2. Age between 3 to 18.

Key Exclusion Criteria:

1. Diagnosis of cerebral palsy/ history of structural brain abnormalities on CT/ MRI or grade III or IV IVH on either side of the brain; genetic/ syndromic disorders.

    

2. A history of seizure or prior electroencephalogram abnormalities related to epilepsy, the use of any psychotropic medications before the study.

Dr. Winnie Wan-Yee Tso

Department of Paediatrics & Adolescent Medicine

wytso@hku.hk

2255 4269

12.4.2 Basic Research (Brain Tumor and extra-CNS solid tumors)

Multi-omic profiling of tumor tissue and liquid biome of pediatric tumors

Key Inclusion Criteria:

1. Pediatric patients with newly diagnosed or recurrent brain and extra-CNS solid tumors.

Dr Anthony Pak-yin Liu

Department of Paediatrics & Adolescent Medicine

apyliu@hku.hk

2255 4806

12.4.3 Basic Research (Nasopharyngeal Carcinoma)

RGC - Targeting Epstein-Barr Virus in Nasopharyngeal Carcinoma: From Mechanistic Study to Novel Therapeutic Development - Multi-institutional basic science study.

Dr Alan Kwok-shing Chiang

Department of Paediatrics & Adolescent Medicine

chiangak@hku.hk

2255 4482

12.4.4 Basic Research

HMRF - Effects on induction of viral lytic cycle in Epstein-Barr virus-associated epithelial malignancies by combining histone deacetylase inhibitor and a novel organic compound grant - Laboratory research study on cell lines and animal models.

Dr Alan Kwok-shing Chiang

Department of Paediatrics & Adolescent Medicine

chiangak@hku.hk

2255 4482