Informations générales (source: ClinicalTrials.gov)
Spartalizumab and Low-dose PAzopanib in Refractory or Relapsed Solid TumOrs of Pediatric and Adults (SPARTO)
Interventional
Phase 1/Phase 2
University Hospital, Bordeaux (Voir sur ClinicalTrials)
mai 2022
novembre 2027
29 juin 2024
Immunotherapies have revolutionized medical oncology following the remarkable and, in
some cases, unprecedented outcomes observed in certain groups of patients with cancer.
However results in adults and mainly in pediatric cancer are still disappointing.
Modulators of angiogenesis, such as VEGF, have a broad range of diverse effects on the
immune system and the tumor micro-environment that are mainly immunosuppressive. In
patients with early-stage disease, anti-VEGF therapy can lead to antitumor effects by
modulating immune mechanisms - provided that therapy is maintained for an adequate length
and tumors are sufficiently immunogenic. Nevertheless, blocking angiogenic molecules
using a strategy based on a single therapeutic approach is likely insufficient to
generate a complete or robust immune response against cancer, especially in patients with
advanced-stage disease.
Based on the results of previous studies which evaluated the safety profile of
spartalizumab, of pazopanib and the combination of antiangiogenic agents with checkpoint
inhibitors, a study combining spartalizumab and low-dose pazopanib in refractory or
relapsed solid tumors of pediatric and adults is proposed. This study will include 2
separate cohorts:
- the pediatric cohort will consist of a phase I study (dose-finding and expansion
phases) combining pazopanib at a fixed dose of 225 mg/m2 and spartalizumab with four
potential candidate doses (2, 3, 4 and 6 mg/kg).
- the adult cohort will consist of a phase II study combining pazopanib at a fixed
dose of 400 mg and spartalizumab at the RP2D of 400 mg every 4 weeks.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/09/2024 13:49:39 | Contacter | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Pablo BERLANGA | 07/06/2024 08:53:08 | Contacter | ||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CHU d'Angers - Unité d'Hématologie et d'Oncologie pédiatrique - Angers - France | Emilie DE CARLI, Dr | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| APHM Hôpital des Enfants La Timone - Hématologie Oncologie Pédiatrique - 13385 - Marseille - France | Nicolas ANDRE, Pr | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - Oncologie Médicale - 69373 - Lyon - France | Mehdi BRAHMI, Dr | Contact (sur clinicalTrials) | |||
| Centre Oscar Lambret - Oncologie pédiatrie - 59020 - Lille - France | Anne-Sophie DEFACHELLES THOMASSIN, Dr | Contact (sur clinicalTrials) | |||
| CHU de Bordeaux - Unité d'Hématologie et d'Oncologie pédiatrique - 33076 - Bordeaux - France | Stéphane DUCASSOU, Pr. | Contact (sur clinicalTrials) | |||
| Institut Bergonié - Oncologie Médicale - 33076 - Bordeaux - France | Antoine ITALIANO, Pr | Contact (sur clinicalTrials) | |||
| Institut d'Hématologie et d'Oncologie Pédiatrique (IHOP) - Oncologie pédiatrique - 69373 - Lyon - France | Nadège CORRADINI, Dr | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
1. For pediatric patients (Cohort 1):
1. Patients should be without standard established therapeutic alternatives at the
time of enrollment suffering from the following conditions :
- refractory or recurrent solid tumor, proven histologically,
- any tumor with high mutational load (> 10 somatic mutations/ Mo) or a high
MSI status,
- tumor, whatever the histology, with proven PDL1 expression (≥1%) or
presence of mature tertiary lymphoid structure (TLS).
2. Age ≥5 and <18 years at inclusion, patients 18 years and older may be included
after discussion with the Sponsor if they have a pediatric
recurrent/refacractory malignancy.
3. Performance status: Karnofsky performance status (for patients >16 years of
age) or Lansky Play score (for patients ≤16 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.
4. Able to swallow tablets.
5. Evaluable or measurable disease as defined by standard imaging criteria for the
patient's tumor type (RECIST v1.1...).
6. Life expectancy ≥ 3 months.
7. Adequate organ function:
- Hematologic 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.
8. Able to comply with scheduled follow-up and with management of toxicity.
9. Females of childbearing potential (WOCBP) 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 a highly effective
contraception during the study and for at least 6 months after the last study
treatment administration. Sexually active male patients must agree to use
condoms during the study and for at least 6 months after the last study
treatment administration.
10. Written informed consent from parents/legal representative and age-appropriate
assent before any study-specific screening procedures are conducted according
to local, regional or national guidelines.
11. Patient affiliated to a social security regimen or beneficiary of the same
according to local requirements.
2. For adults patients:
- Pre-screening phase:
1. adults (≥ 18 years old) with refractory or recurrent solid tumor (include
rhabdomyosarcoma, Ewing's sarcoma, osteosarcoma and other) and/or tumor
with High mutation rate (>10 somatic mutations/Mb) and/or suffering of
Mismatch repair-deficient syndrome.
2. Adult patients with an ECOG score of 0/1. 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.
3. Evaluable or measurable disease as defined by standard imaging criteria
for the patient's tumor type (RECIST v1.1...).
4. Written informed consent from patient before any study-specific screening
procedures are conducted according to local, regional or national
guidelines.
- Screening phase (Cohort 2):
1. adults without standard established therapeutic alternatives at the time
of enrollment suffering from refractory or recurrent advanced solid tumor
characterized by the presence of mature TLS
2. Age ≥ 18 years at inclusion
3. Adult patients with an ECOG score of 0/1. 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.
4. Evaluable or measurable disease as defined by standard imaging criteria
for the patient's tumor type (RECIST v1.1...).
5. Life expectancy ≥ 3 months
6. Adequate organ function:
- Hematologic 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% 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.
g. Able to comply with scheduled follow-up and with management of toxicity. h.
Females of childbearing potential (WOCBP) 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 a highly effective
contraception during the study and for at least 6 months after the last study
treatment administration. Sexually active male patients must agree to use
condoms during the study and for at least 6 months after the last study
treatment administration.
i. Written informed consent from patient before any study-specific screening
procedures are conducted according to local, regional or national guidelines.
j. Patient affiliated to a social security regimen or beneficiary of the same
according to local requirements.
1. For pediatric patients (Cohort 1):
1. Patients should be without standard established therapeutic alternatives at the
time of enrollment suffering from the following conditions :
- refractory or recurrent solid tumor, proven histologically,
- any tumor with high mutational load (> 10 somatic mutations/ Mo) or a high
MSI status,
- tumor, whatever the histology, with proven PDL1 expression (≥1%) or
presence of mature tertiary lymphoid structure (TLS).
2. Age ≥5 and <18 years at inclusion, patients 18 years and older may be included
after discussion with the Sponsor if they have a pediatric
recurrent/refacractory malignancy.
3. Performance status: Karnofsky performance status (for patients >16 years of
age) or Lansky Play score (for patients ≤16 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.
4. Able to swallow tablets.
5. Evaluable or measurable disease as defined by standard imaging criteria for the
patient's tumor type (RECIST v1.1...).
6. Life expectancy ≥ 3 months.
7. Adequate organ function:
- Hematologic 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.
8. Able to comply with scheduled follow-up and with management of toxicity.
9. Females of childbearing potential (WOCBP) 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 a highly effective
contraception during the study and for at least 6 months after the last study
treatment administration. Sexually active male patients must agree to use
condoms during the study and for at least 6 months after the last study
treatment administration.
10. Written informed consent from parents/legal representative and age-appropriate
assent before any study-specific screening procedures are conducted according
to local, regional or national guidelines.
11. Patient affiliated to a social security regimen or beneficiary of the same
according to local requirements.
2. For adults patients:
- Pre-screening phase:
1. adults (≥ 18 years old) with refractory or recurrent solid tumor (include
rhabdomyosarcoma, Ewing's sarcoma, osteosarcoma and other) and/or tumor
with High mutation rate (>10 somatic mutations/Mb) and/or suffering of
Mismatch repair-deficient syndrome.
2. Adult patients with an ECOG score of 0/1. 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.
3. Evaluable or measurable disease as defined by standard imaging criteria
for the patient's tumor type (RECIST v1.1...).
4. Written informed consent from patient before any study-specific screening
procedures are conducted according to local, regional or national
guidelines.
- Screening phase (Cohort 2):
1. adults without standard established therapeutic alternatives at the time
of enrollment suffering from refractory or recurrent advanced solid tumor
characterized by the presence of mature TLS
2. Age ≥ 18 years at inclusion
3. Adult patients with an ECOG score of 0/1. 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.
4. Evaluable or measurable disease as defined by standard imaging criteria
for the patient's tumor type (RECIST v1.1...).
5. Life expectancy ≥ 3 months
6. Adequate organ function:
- Hematologic 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% 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.
g. Able to comply with scheduled follow-up and with management of toxicity. h.
Females of childbearing potential (WOCBP) 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 a highly effective
contraception during the study and for at least 6 months after the last study
treatment administration. Sexually active male patients must agree to use
condoms during the study and for at least 6 months after the last study
treatment administration.
i. Written informed consent from patient before any study-specific screening
procedures are conducted according to local, regional or national guidelines.
j. Patient affiliated to a social security regimen or beneficiary of the same
according to local requirements.
For pediatric and adult patients (Cohorts 1 and 2):
1. Patients treated with anti-PD1 immunotherapy within 6 months prior to starting study
treatment; patients treated with anti-PD1 for more than 6 months remain eligible for
inclusion, provided that this treatment has brought the patient clinical benefit
(objective response or stable disease > 4 months).
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
arrhythmia, e.g. ventricular, supraventricular, nodal arrhythmias, or conduction
abnormality), unstable ischemia, congestive heart failure within 12 months of
screening).
4. Uncontrolled hypertension
5. Active viral hepatitis or known human immunodeficiency virus (HIV) infection or any
other uncontrolled infection.
6. Presence of any ≥ CTCAE grade 2 treatment-related toxicity with the exception of
alopecia, ototoxicity or peripheral neuropathy.
7. Systemic anticancer therapy within 21 days of the first study dose or 5 times its
half-life, whichever is less.
8. Previous myeloablative therapy with autologous hematopoietic stem cell rescue within
8 weeks of the first study drug dose
9. 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.
10. Radiotherapy (non-palliative) within 21 days prior to the first dose of drug (or
within 6 weeks for therapeutic doses of MIBG)
11. 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.
12. Currently taking medications with a known risk of prolonging the QT interval or
inducing Torsades de Pointes
13. High dose chemotherapy followed by peripheral stem cell transplantation within less
than 6 months.
14. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 14 days prior to the first dose of study
treatment. The use of physiologic doses of corticosteroids (up to 0.25 mg/kg daily
prednisone equivalent) may be approved after consultation with the Sponsor.
15. Diagnosis of prior or active autoimmune disease.
16. Evidence of interstitial lung disease.
17. Unable to taper steroids due to ongoing mass effect; a maximum dexamethasone dose of
0.05 mg/kg/day is allowed, but preferably have been discontinued.
18. Known hypersensitivity to any study drug or component of the formulation.
19. Persons referred to in Articles L. 1121-5, L. 1121-6, L. 1121-8 and L. 11221-1-2 of
the Public Health Code (pregnant women, parturient and nursing mothers; persons
deprived of their liberty by a judicial or administrative decision, persons
hospitalized without consent and persons admitted to a health or social
establishment for purposes other than that of research; adults subject to a legal
protection measure or incapacitated express consent; people in emergency situations
who cannot give prior consent)
20. Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study
drug.