Informations générales (source: ClinicalTrials.gov)
European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART)
Interventional
Phase 1/Phase 2
Gustave Roussy, Cancer Campus, Grand Paris (Voir sur ClinicalTrials)
août 2016
août 2027
29 juin 2024
This proof-of-concept platform trial is designed to cover the targeting of several
survival pathways in oncogenesis that are currently not adequately employed for pediatric
patients in Europe (Geoerger 2017; Geoerger 2019).
The aims of the trial are:
1. To determine the recommended phase II dose (RP2D) of a specific anticancer agent
and/or a relevant combination in a pediatric population, to document its
tolerability and
2. To explore first signals of activity in a molecularly enriched study population.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/12/2024 12:44:25 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Birgit GEOERGER | 10/06/2024 08:04:03 | Contacter | ||
Critères
Tous
Inclusion Criteria:
1. Patients must be diagnosed with a haematologic or solid tumor malignancy that has
progressed despite standard therapy, or for which no effective standard therapy
exists.
2. Age < 18 years at inclusion; patients 18 years and older may be included after
discussion with the sponsor if they have a pediatric recurrent/refractory
malignancy.
3. Patient must have had advanced molecular profiling (i.e. WES/WGS +/- RNAseq) of
their recurrent or refractory tumor i.e. at the time of disease progression/relapse;
exceptionally patients with advanced molecular profiling at diagnosis may be
allowed.
4. Evaluable or measurable disease as defined by standard imaging criteria for the
patient's tumor type (RECIST v1.1, RANO criteria for patients with HGG, INRC
criteria for patients with NB, Leukemia criteria, etc.).
5. Patients with relapsed or refractory leukemia are eligible for this study.
6. Performance status: Karnofsky performance status (for patients >12 years of age) or
Lansky Play score (for patients ≤12 years of age) ≥ 70%. Patients who are unable to
walk because of paralysis or stable neurological disability, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the
performance score.
7. Life expectancy ≥ 3 months
8. Adequate organ function:
Hematologic criteria (Leukemia patients are excluded from hematological criteria):
- Peripheral absolute neutrophil count (ANC) ≥ 1000/μL(unsupported)
- Platelet count ≥ 100,000/μL (unsupported)
- Hemoglobin ≥ 8.0 g/dL (transfusion is allowed)
Cardiac function:
- Shortening fraction (SF) >29% (>35% for children < 3 years) and left
ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by
echocardiography (mandatory only for patients who have received cardiotoxic
therapy).
- Absence of QTc prolongation (QTc > 450 msec on baseline ECG, using the
Fridericia correction [QTcF formula]) or other clinically significant
ventricular or atrial arrhythmia.
Renal and hepatic function:
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age
- Total bilirubin ≤ 1.5 x ULN
- Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 2,5
x ULN; aspartate aminotransferase (AST)/serum glutamic oxaloacetic
transaminase/SGOT ≤ 2,5 x ULN except in patients with documented tumor
involvement of the liver who must have AST/SGOT and ALT/SGPT ≤ 5 x ULN.
9. Able to comply with scheduled follow-up and with management of toxicity.
10. Females of childbearing potential must have a negative serum or urine pregnancy test
within 72 hours prior to initiation of treatment. Sexually active women of
childbearing potential must agree to use acceptable and appropriate contraception
during the study and for at least 6 months after the last study treatment
administration. Sexually active males patients must agree to use condom during the
study and for at least 6 months (7 months for arm J) after the last study treatment
administration. Acceptable contraception are defined in CTFG Guidelines
"Recommendations related to contraception and pregnancy testing in clinical trials"
11. For all oral medications patients must be able to comfortably swallow capsules
(except for those for which an oral solution is available); nasogastric or
gastrostomy feeding tube administration is allowed only if indicated.
12. Written informed consent from parents/legal representative, patient, and
age-appropriate assent before any study-specific screening procedures are conducted
according to local, regional or national guidelines.
13. Patient affiliated to a social security regimen or beneficiary of the same according
to local requirements.
1. Patients must be diagnosed with a haematologic or solid tumor malignancy that has
progressed despite standard therapy, or for which no effective standard therapy
exists.
2. Age < 18 years at inclusion; patients 18 years and older may be included after
discussion with the sponsor if they have a pediatric recurrent/refractory
malignancy.
3. Patient must have had advanced molecular profiling (i.e. WES/WGS +/- RNAseq) of
their recurrent or refractory tumor i.e. at the time of disease progression/relapse;
exceptionally patients with advanced molecular profiling at diagnosis may be
allowed.
4. Evaluable or measurable disease as defined by standard imaging criteria for the
patient's tumor type (RECIST v1.1, RANO criteria for patients with HGG, INRC
criteria for patients with NB, Leukemia criteria, etc.).
5. Patients with relapsed or refractory leukemia are eligible for this study.
6. Performance status: Karnofsky performance status (for patients >12 years of age) or
Lansky Play score (for patients ≤12 years of age) ≥ 70%. Patients who are unable to
walk because of paralysis or stable neurological disability, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the
performance score.
7. Life expectancy ≥ 3 months
8. Adequate organ function:
Hematologic criteria (Leukemia patients are excluded from hematological criteria):
- Peripheral absolute neutrophil count (ANC) ≥ 1000/μL(unsupported)
- Platelet count ≥ 100,000/μL (unsupported)
- Hemoglobin ≥ 8.0 g/dL (transfusion is allowed)
Cardiac function:
- Shortening fraction (SF) >29% (>35% for children < 3 years) and left
ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by
echocardiography (mandatory only for patients who have received cardiotoxic
therapy).
- Absence of QTc prolongation (QTc > 450 msec on baseline ECG, using the
Fridericia correction [QTcF formula]) or other clinically significant
ventricular or atrial arrhythmia.
Renal and hepatic function:
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age
- Total bilirubin ≤ 1.5 x ULN
- Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 2,5
x ULN; aspartate aminotransferase (AST)/serum glutamic oxaloacetic
transaminase/SGOT ≤ 2,5 x ULN except in patients with documented tumor
involvement of the liver who must have AST/SGOT and ALT/SGPT ≤ 5 x ULN.
9. Able to comply with scheduled follow-up and with management of toxicity.
10. Females of childbearing potential must have a negative serum or urine pregnancy test
within 72 hours prior to initiation of treatment. Sexually active women of
childbearing potential must agree to use acceptable and appropriate contraception
during the study and for at least 6 months after the last study treatment
administration. Sexually active males patients must agree to use condom during the
study and for at least 6 months (7 months for arm J) after the last study treatment
administration. Acceptable contraception are defined in CTFG Guidelines
"Recommendations related to contraception and pregnancy testing in clinical trials"
11. For all oral medications patients must be able to comfortably swallow capsules
(except for those for which an oral solution is available); nasogastric or
gastrostomy feeding tube administration is allowed only if indicated.
12. Written informed consent from parents/legal representative, patient, and
age-appropriate assent before any study-specific screening procedures are conducted
according to local, regional or national guidelines.
13. Patient affiliated to a social security regimen or beneficiary of the same according
to local requirements.
1. Patients with symptomatic central nervous system (CNS) metastases who are
neurologically unstable or require increasing doses of corticosteroids or local
CNS-directed therapy to control their CNS disease. Patients on stable doses of
corticosteroids for at least 7 days prior to receiving study drug may be included.
2. Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, or malabsorption syndrome).
3. Clinically significant, uncontrolled heart disease (including history of any cardiac
arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction
abnormality, unstable ischemia,congestive heart failure within 12 months of
screening)
4. Active viral hepatitis or known human immunodeficiency virus (HIV) infection or any
other uncontrolled infection.
5. Presence of any ≥ CTCAE grade 2 treatment-related toxicity with the exception of
alopecia, ototoxicity or peripheral neuropathy.
6. Systemic anticancer therapy within 21 days of the first study dose or 5 times its
half-life, whichever is less.
7. Previous myeloablative therapy with autologous hematopoietic stem cell rescue within
8 weeks of the first study drug dose
8. Allogeneic stem cell transplant within 3 months prior to the first study drug dose.
Patients receiving any agent to treat or prevent graft-versus host disease (GVHD)
post bone marrow transplant are not eligible for this trial.
9. Radiotherapy (non-palliative) within 21 days prior to the first dose of drug (or
within 6 weeks for therapeutic doses of MIBG or craniospinal irradiation).
10. Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal
shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous
access devices are not considered major surgery, but for these procedures, a 48 hour
interval must be maintained before the first dose of the investigational drug is
administered.
11. Currently taking medications with a known risk of prolonging the QT interval or
inducing Torsades de Pointes (Refer to Appendix 8).
12. Currently taking medications that are mainly metabolized by CYP3A4/5, CYP2C8,
CYP2C9, CYP2C19, CYP2D6 or the drug transporters Pgp (MDR1), BCRP, OATP1B1, OATP1B3,
OCT1 and OCT2 and have a low therapeutic index that cannot be discontinued at least
7 days or 5 x reported elimination half-life prior to start of treatment with any of
the investigational drugs and for the duration of the study (Refer to Appendix 9).
13. Known hypersensitivity to any study drug or component of the formulation.
14. Pregnant or nursing (lactating) females.
15. Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study
drug.