| 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 11.4-14.7 36-46 80-96 11.9-14.6 150-350 4.5-13.5
12- <18 years male 12.4-16.4 40-51 80-96 11.9-13.7 150-350 4.5-13.5
> 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 < 2 or Karnofsky performance ≳ 50. < 16 years, Lansky performance score > 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 time must be < 1.5 × ULN; activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless undergoing anticoagulation therapy.
11. Laboratory values (Liver): Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 × ULN; Bilirubin ≤ 2 × ULN or ≤ 5 × ULN for all patients.
12. Cardiovascular values (Heart): Patients will be ineligible if they have medical history of an arterial thrombotic event, stroke, or transient ischemic attack within the past 12 months; medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or a cardiac arrhythmia that required treatment within the past 12 months; medical history of myocardial infarction or unstable angina within 6 months before Cycle 1 Day 1; QTcF prolongation to > 470 ms in women and > 450 ms in men based on a 12-lead electrocardiogram (ECG) in triplicate using the Fridericia formula: QTc = QT / RR1/3.
13. Pulmonary values (Lungs): No evidence of acute respiratory failure (PaO2 <65 mmHg on room air, or PaCO2 ≥ 50 or pH<7.35), chronic bronchitis (FEV1 ≤ 60% predicted or FVC ≤ 60%), acute bronchitis (increase in cough, sputum production, and sputum color within prior 5 days).
Neuroendocrine Prostate Cancer (NEPC) inclusion criteria:
14. Neuroendocrine Prostate Cancer (NEPC)
15. Histologically or cytologically documented findings consistent with NEPC not amenable to curative surgery, radiation, or other therapy.
16. Prior treatment (for advanced, metastatic or [neo]adjuvant) should have included a taxane and/or anthracycline-based therapy, androgen receptor inhibitor, androgen deprivation therapy and, where appropriate, an approved checkpoint inhibitor.
17. MYCN positivity by histology (+, ++, +++)
Small Cell Lung Cancer (SCLC) inclusion criteria:
23. Histologically or cytologically documented findings consistent with small cell lung cancer not amenable to curative surgery, radiation, or other therapy.
24. Failed the standard-of-care treatment for SCLC : Cisplatin or Carboplatin, etoposide , atezolizumab, durvalumab, Tarlatamab
MYCN positivity by histology (+, ++, +++)
Glioblastoma Multiforme (GBM) inclusion criteria:
28. Histologically or cytologically documented findings consistent with glioblastoma multiforme not amenable to curative surgery, radiation, or other therapy.
29. Failed radiation and chemotherapy including temozolomide and bevacizumab.
30. MYCN positivity by histology (+, ++, +++)
High grade serous ovarian cancer inclusion criteria:
31. Histologically or cytologically documented findings consistent with ovarian cancer not amenable to curative surgery, radiation, or other therapy.
32. Failed platinum-based chemotherapy, such as cisplatin or carboplatin and in combination with a taxane (paclitaxel/docetaxel)
33. MYCN positivity by histology (+, ++, +++)
T-Cell Acute Lymphoblastic Leukaemia inclusion criteria:
Histological diagnosis of ALL
Past history or not of radiation therapy
Past history of chemotherapy (methotrexate, vincristine, dexamethasone)
Past history of antibody drug conjugate treatment
MYCN (+, ++, +++)
Basal Cell Carcinoma
Histological diagnosis of Basal Cell Carcinoma
Past history or not of radiation therapy, phototherapy)
Past history of chemotherapy (5-Fluorouracil, imiquimod)
Past history of antibody drug conjugate treatment
MYCN (+, ++, +++)
Spinal Ependymoma
Histological diagnosis of Spinal ependymoma
Past history or not of radiation therapy
Past history of chemotherapy (temozolomide, lapatinib)
Past history of antibody drug conjugate treatment
MYCN (+, ++, +++)
Sarcomas
Histological diagnosis of Sarcomas
Past history or not of radiation therapy
Past history of chemotherapy (Doxorubicin, ifosfamide, epirubicin, gemicitabine,docetaxel, dacarbazine
Pazopanib, imatinib, sorafenib)
Past history of antibody drug conjugate treatment
MYCN (+, ++, +++)
Triple Negative Breast Cancer (TNBC)
1. Triple negative breast cancer status confirmed on histology (HER2-, PR-, ER-)
2. Histologically or cytologically documented findings consistent with TNBC not amenable to curative surgery, radiation, or other therapy.
3. Prior treatment (for advanced, metastatic or [neo]adjuvant) should have included a taxane and/or anthracycline-based therapy and, where appropriate, an approved checkpoint inhibitor.
4. MYCN positivity by histology (+, ++, +++)
5. Presence or absence of PD-L1 by histology
|
Exclusion criteria
1 Abnormal cardiac function: left ventricular ejection fraction (LVEF) < 55%, fractional shortening fraction (FS) < 28%.
2 Uncontrolled cardiac arrhythmia.
3 QTc prolongation on ECG.
4 Abnormal neurologic function: In patients ≳ 16 years, ECOG/WHO performance status > 2 or Karnofsky performance < 50. In patients < 16 years, Lansky performance score < 50%.
5 History of cerebrovascular accident.
6 Evidence of brain metastasis.
7 History of coagulopathy or platelet disorders.
7 History of autoimmune disorder.
9 Pregnant or breastfeeding.
10 Trying to conceive/refusing contraceptive use during the study period (in sexually active patients).
Exclusion Criteria for Adults:
1. Previous mRNA drug treatment or currently being treated with other investigational agents.
2. Liver dysfunction or failure, renal failure, or severe cardio-respiratory disease.
3. Baseline reticulocytosis or monocytosis (>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.
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80 and over: 80+ Year,Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Child: 6 Year-12 Year,Infant: 1 Month(s)-12 Month(s),Infant: 13 Month(s)-24 Month(s),Middle Aged: 45 Year(s)-64 Year(s),New born: 0 Day-1 Month,Preschool Child: 2 Year-5 Year |
6 Month(s) |
100 Year(s) |
Both |