Cancer Paediatrics
Conditions
Interventions
3UTRMYCN M14
Sponsors
UTR Therapeutics Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria For Childhood and Adolescent Cancers 1 6months-12 years, male and female., 13-18yrs male & female. 2 Diagnosis of Rhabdomyosarcoma, Neuroblastoma, Retinoblastoma, Wilms tumor, Medulloblastoma, and Acute lymphoblastic leukaemia 3 Fresh Tumor tissues or slides or blocks must be available for retrospective analysis. 4 Tumor biomarkers: MYCN+ tumor confirmed by IHC and or qPCR MYOD1+/- tumor confirmed by IHC and or qPCR TP53 +/- tumor confirmed by IHC and or qPCR 8 Measurable disease by RECIST version 1.1 9 Must have received previous treatment with the following medications: Olaparib, actinomycin D, cisplatin, cyclophosphamide, bevacizumab, epirubicin and paclitaxel. 10 Adequate bone marrow function: HB (g/dl) HCT (%) MCV (fl) RDW (%) PLT (10^3ml) WBC (10^3/ml) 6 months-2 years 11-13.5 31-42 73-85 12.3-15.6 150-350 6-17 2-6 years 11-13.7 34-44 75-86 12-14.6 150-350 5-15.5 6-12 years 11.2-14.5 35-44 78-90 11.9-13.8 150-350 4.5-13.5 12- 18 years female 12-14 36-41 80-90 150-350 4.5-11 > 18 years male 13.5-15.5 41-47 80-90 150-350 4.5-11 11 Adequate cardiac function: left ventricular ejection fraction (LVEF) ? 55%, fractional shortening fraction (FS) ? 28% 12 Adequate neurologic function: In patients ? 16 years, ECOG/WHO performance status 50%. 13 No history of autoimmune disorder. 14 No history of coagulation or platelet disorders. 15 Able to receive medication intravenously. 16 Not pregnant or trying to conceive. 17 Not breastfeeding. Ability to give to informed consent or assent to consent. Rhabdomyosarcoma: Histological diagnosis of rhabdomyosarcoma (embryonal or alveolar) Past history or not of Surgery Past history or not of radiation therapy Past history of chemotherapy: Vincristine, Actinomycin D, Cyclophosphamide treatment Inclusion Criteria for Adults: 1. Adult patients (>18 years) 2. Biopsy-confirmed diagnosis of , neuroendocrine prostate cancer, Small Cell Lung Cancer, Glioblastoma multiforme, Spinal Ependymoma, T-cell acute lymphoblastic leukaemia, high grade serous ovarian cancer, basal cell carcinoma, Sarcomas, triple negative breast cancer (TNBC). 3. MYCN positivity (+, ++, +++) tested by histology at trial enrolment, or history of prior histologic diagnosis. 4. treatment for their cancer type with incurable advanced disease. 5. Performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) 6. Able to provide written informed consent at the time of study enrolment. 7. Participants who are physically able to become pregnant must use an effective form of birth control from 14 days prior to enrollment through 6 months following the last dose of 3’UTRMYCN M1-14. Participants who can father a child must use an effective form of birth control from Day 0 through 3 months following the last dose of 3’UTRMYCN M1-14. 8. Laboratory values (Hematology): Absolute neutrophil count = 1,000 cells/mm3; Platelet count = 75,000 cells/mm3; Hemoglobin = 8.0 g/dL. 9. Laboratory values (Renal): Serum creatinine < 1.5 × upper limit of normal (ULN) or creatinine clearance = 40 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation 10. Laboratory values (Coagulation): Prothrombin/International Normalized Ratio (PT/INR) or prothrombin ti
Exclusion criteria
Exclusion criteria: Exclusion criteria 1 Abnormal cardiac function: left ventricular ejection fraction (LVEF) 2 or Karnofsky performance 2xULN). 4. Significant medical illnesses that in the investigator’s opinion cannot be adequately controlled or would compromise the patient’s ability to tolerate therapy (e.g., history of allergic reactions attributed to compounds of similar chemical or biologic composition to 3’UTRMYCN M1-14). 5. Any history of other malignancies, unless in complete remission and off all therapy for that disease for a minimum of 3 years. 6. History of thromboembolic disorder or deep vein thrombosis, unless resolved and off therapeutic anticoagulation. 7. Presence of abnormal hematological or biochemical parameters as defined in this protocol (e.g., anemia, thrombocytopenia). 8. Active infection currently being treated with systemic antibiotics. 9. Pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 8.6.1 Primary Outcome Measures 8.6.1.1 Safety and Tolerability 1.Measure: I.Incidence, severity, and nature of treatment-emergent adverse events (TEAEs) and dose-limiting toxicities (DLTs). 2.Assessment Method: I.Adverse events (AEs) and serious adverse events (SAEs) will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). II.DLTs will be assessed during Cycle 1 (first 28 days) of treatment to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). III.Continuous monitoring of vital signs, laboratory parameters (hematology, liver/kidney function tests), electrocardiograms (ECG), and echocardiography. 3.Justification: I.Safety is the primary goal of a Phase 1 trial. II.The 3+3 dose-escalation design requires real-time assessment of DLTs to guide dose modifications and escalation. 8.6.1.2 Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) 1.Measure: I.Identification of the highest dose level at which =1 of 6 patients experiences a DLT. 2.Assessment Method: I.MTD will be determined through dose-escalation using the 3+3 design. II.RP2D will be selected based on MTD data, pharmacokinetics (PK), and additional safety/tolerability data from the dose-expansion phase. 3.Justification: I.Establishing the optimal dose is critical for advancing 3’UTRMYCN M1-14 to later-stage trials. 8.6.2 Secondary Outcome Measures 8.6.2.1 Preliminary Anti-Tumor Efficacy 1.Measure: I.Overall response rate (ORR) = (Complete Response [CR] + Partial Response [PR]) / Total efficacy-evaluable patients. II.Disease Control Rate (DCR) = (CR + PR + Stable Disease [SD]) / Total efficacy-evaluable patients. III.Progression-Free Survival (PFS): Time from treatment initiation to disease progression or death. IV.Overall Survival (OS): Time from treatment initiation to death from any cause. V.Duration of Response (DoR): Time from first response (CR/PR) to disease progression. 2.Assessment Method: I.Tumor response will be evaluated u | — |
Secondary
| Measure | Time frame |
|---|---|
| 8.6.2 Secondary Outcome Measures 8.6.2.1 Preliminary Anti-Tumor Efficacy 1. Measure: I. Overall response rate (ORR) = (Complete Response [CR] + Partial Response [PR]) / Total efficacy-evaluable patients. II. Disease Control Rate (DCR) = (CR + PR + Stable Disease [SD]) / Total efficacy-evaluable patients. III. Progression-Free Survival (PFS): Time from treatment initiation to disease progression or death. IV. Overall Survival (OS): Time from treatment initiation to death from any cause. V. Duration of Response (DoR): Time from first response (CR/PR) to disease progression. 2. Assessment Method: I. Tumor response will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). II. Imaging studies (MRI/CT scans) will be conducted at baseline, every 8 weeks, and upon disease progression. 3. Justification: I. Although a Phase 1 trial focuses primarily on safety, evaluating early efficacy signals helps determine whether further clinical development is warranted. 8.6.2.2 Pharmacokinetics (PK) Profile 1. Measure: I. Peak plasma concentration (Cmax). II. Time to peak concentration (Tmax). III. Area under the concentration-time curve (AUC). IV. Clearance (CL) and half-life (T½). 2. Assessment Method: I. Serial blood sampling at predefined time points post-dose. II. Drug concentration measured using liquid chromatography-mass spectrometry (LC-MS/MS). 3. Justification: I. PK analysis ensures the selected RP2D achieves therapeutic exposure while minimizing toxicity. 8.6.2.3 Pharmacodynamic (PD) Profile 1. Measure: I. MYCN mRNA degradation levels. II. MYCN protein downregulation. 2. Assessment Method: I. Tumor biopsy analysis (pre-treatment and on-treatment) using: a. Quantitative PCR (qPCR) for MYCN mRNA expression. b. Western blotting and immunohistochemistry (IHC) for MYCN protein reduction. 3. Justification: I. Confirming target engagement ensures that 3’UTRMYCN M1-14 is achieving its intended biological effect. 8.6.2.4 Imm | — |
Countries
Nigeria
Contacts
Public ContactDavid Asuzu
Chief Medical Officer
Outcome results
None listed