Phase I/II Evaluation of Sodium 2-Hydroxylinoleate in Pediatric Relapsed/Refractory Neuroblastoma and Solid Tumors, Alone and with Chemotherapy or Targeted Therapies
- Trial ID
- 2023-504246-64-00
- Protocol
- ETNA
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this phase I/II clinical trial is to define the **paediatric recommended phase 2 dose (RP2D)** of ABTL0812, both as a single agent and in combination with chemotherapy (irinotecan-temozolomide) or targeted therapies, in children with relapsed/refractory neuroblastoma and other solid tumors. Establishing the RP2D is clinically relevant as it determines the optimal dosing regimen that maximizes therapeutic efficacy while minimizing adverse effects, thereby guiding subsequent phases of clinical development.
Secondary objectives include evaluating the safety profile, antitumor activity, progression-free survival, overall survival, pharmacokinetics, and pharmacodynamics of ABTL0812 in the pediatric population. These assessments are crucial for understanding the broader clinical impact of ABTL0812, including its potential to improve patient outcomes and its mechanism of action in the context of pediatric oncology.
Participants
The clinical trial involves a study population comprising both **male** and **female** participants aged between 1 and 21 years, diagnosed with **relapsed/refractory neuroblastoma** and other solid tumors. The trial aims to define the pediatric recommended phase 2 dose of ABTL0812, both as a single agent and in combination with chemotherapy or targeted therapies. Participants were selected based on specific inclusion criteria, including the ability to swallow intact capsules and having a solid tumor that has progressed, relapsed, or is refractory to at least one standard therapy. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are required to have adequate performance status and haematological, hepatic, and renal function. Lifestyle considerations such as diet and physical activity are not specified. Key inclusion criteria include appropriate contraceptive methods for sexually active individuals and a negative pregnancy test for women of childbearing age. The absence of psychological, sociological, or geographical conditions that could hinder compliance with the study protocol is also required.
Plans and Procedures
The clinical trial is designed as a **phase I/II** study to evaluate the safety and efficacy of **sodium 2-hydroxylinoleate** in pediatric patients with relapsed or refractory **neuroblastoma** and other solid tumors. The trial employs a **randomized, double-blind, controlled** methodology to ensure unbiased results. The primary objective is to define the recommended phase 2 dose (RP2D) of the investigational drug, both as a single agent and in combination with chemotherapy or targeted therapies. The trial is expected to run until December 2028, with recruitment starting in December 2023.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as age, ability to swallow capsules, and adequate organ function. Following successful screening, participants will be enrolled and randomized into treatment cohorts. The study includes multiple follow-up visits to monitor safety, efficacy, and any dose-limiting toxicities, particularly during the first cycle of treatment. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted to evaluate the overall outcomes of the treatment.
The expected length of participant involvement varies depending on individual response and tolerance to the treatment, but it generally spans several months. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial is structured to ensure rigorous monitoring and adherence to ethical standards, with informed consent obtained from all participants or their legal guardians prior to any study-specific procedures.
Treatment
The clinical trial involves the experimental medication **ABTL0812**, which is a **sodium 2-hydroxylinoleate** compound. This investigational drug is formulated as a **capsule** and is intended for oral administration. The trial aims to determine the recommended phase 2 dose (RP2D) of ABTL0812 in pediatric patients. The medication is classified as an oncological agent and has been designated as an orphan drug under the designation number EU/3/15/1485. The pharmaceutical form of the drug is specifically designed for pediatric use, and it is produced by ABILITY PHARMACEUTICALS, S.L. The active substance, sodium 2-hydroxylinoleate, is of chemical origin.
In addition to the experimental treatment, the study may involve the use of standard-of-care therapies, including chemotherapy agents such as irinotecan and temozolomide, or other targeted therapies. These non-experimental treatments are used in combination with ABTL0812 to evaluate the efficacy and safety of the investigational drug in children with relapsed or refractory neuroblastoma and other solid tumors. The dosing schedule and participant compliance will be closely monitored throughout the trial to ensure accurate assessment of the treatment's effects.
Efficacy
Efficacy in the clinical trial of ABTL0812 for children with relapsed or refractory neuroblastoma and other solid tumors will be assessed primarily through the **incidence of dose-limiting toxicities**. This parameter will be evaluated during the first cycle of study treatment for cohorts A and B. The trial aims to define the pediatric recommended phase 2 dose (RP2D) of ABTL0812, both as a single agent and in combination with chemotherapy or targeted therapies. The assessment of dose-limiting toxicities will provide critical data on the safety and tolerability of the treatment, which are essential for determining the appropriate dosing regimen for further phases of the trial.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Yet Recruiting | 04 Dec 2023 | 48 |