A phase I/II trial of ABTL0812 in children with relapsed/refractory neuroblastoma and other solid tumours

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2023-10-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Defining the paediatric recommended phase 2 dose (RP2D) of ABTL0812 as single agent and in combination with chemotherapy (irinotecan-temozolomide) or targeted
therapies.

Secondary objectives 1

1. Evaluating safety, antitumour activity, progression free survival, overall survival, pharmacokinetics and pharmacodynamics of ABTL0812 in children.

Conditions and MedDRA coding

Relapsed/refractory neuroblastoma and other solid tumours

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Signed informed consent of the patient, parents or legal representatives before any study-specific screening procedures are conducted, and age-appropriate assent. 2. Aged 1 to ≤21 years at time of signing informed consent. 3. BSA ≥0.5 m2 . 4. Patient must be able to swallow intact capsules. 5. Diagnosis of a solid tumour that has progressed, relapsed or is refractory to at least one standard therapy and/or for which there is not known curative option. Histologic confirmation of progression or relapse is recommended but not mandatory. 6. At least one evaluable or measurable radiological site of disease as defined by INRC, RECIST v1.1 or RAPNO criteria. 7. Adequate performance status: Patients 60%. Patients ≥16 years of age: Karnofsky >60%. 8. Adequate haematological, hepatic and renal function defined by the following laboratory results obtained within 7 days prior to initiation of study drug according to CTCAE v5.0: *Haematological function: - Haemoglobin ≥ 8 g/dL (transfusion allowed). - Peripheral ANC ≥1x109 /L. No G-CSF support for 72 hours prior to initiation of study treatment. Pegylated forms need a wash-out of 7 days. - Platelet count ≥75x109 /L, unsupported for 72 hours prior to initiation of study treatment. *Renal and liver function: - Normal serum creatinine based on age/gender. If serum creatinine is greater than maximum serum creatinine for age/gender, then creatinine clearance (or radioisotope glomerular filtration rate [GFR]) must be >70 mL/min/1.73m2 . - Total bilirubin ≤1.5 x ULN (≤3 x ULN if liver metastases). - AST or ALT ≤3 x ULN (≤5 x ULN if liver metastases). 9. Appropriate contraceptive methods for sexually active males and women of childbearing age. 10. A negative pregnancy test for women of childbearing age. 11. Absence of any psychological, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up Schedule

Exclusion criteria 1

1. 1. Symptomatic or bleeding CNS metastases that result in a neurologically unstable clinical state or require increasing doses of corticosteroids or local CNS-directed therapy to control. 2. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that in the opinion of the investigator might affect the absorption of ABTL0812 or temozolomide. 3. Any additional uncontrolled illness or known active infection, including HBV, HCV and HIV. 4. Presence of any grade >2 clinically significant toxicities related to prior treatments with the exception of alopecia, peripheral neuropathy or other long-term sequelae of cancer therapy, and parameters otherwise permitted in the inclusion criteria. 5. Any uncontrolled medical condition or other identified abnormality that precludes the patient's safe participation in and completion of the study, as judged by the investigator. 6. Systemic anticancer therapy within 21 days or 5 half-lives, whichever is shorter, prior to initiation of study treatment. Seven days for oral metronomic chemotherapy. 7. I-131 MIBG therapy within 6 weeks prior to initiation of study treatment. 8. Myeloablative therapy with autologous hematopoietic stem cell rescue within 60 days or allogeneic hematopoietic stem cell rescue within 120 days of study treatment initiation. 9. Active graft versus host disease requiring systemic therapy. 10. Radiotherapy (non-palliative) within 21 days prior to study treatment initiation. 11. Major surgical procedure within 21 days of study treatment initiation, or anticipated need for major surgical procedure during the course of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of dose limiting toxicities assessed during the first cycle of study treatment of ABTL0182 (cohorts A and B).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron

Sponsor organisation

Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron

Address

Passeig De La Vall D'hebron 119-129

City

Barcelona

Postcode

08035

Country

Spain

Scientific contact point

Organisation

Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron

Contact name

Angélica Valderrama Rodríguez

Public contact point

Organisation

Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron

Contact name

Angélica Valderrama Rodríguez

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications