Refractory or Recurrent Solid TumorPhase 1/2SPARTONCT05210413
Spartalizumab and Low-dose PAzopanib in Refractory or Relapsed Solid TumOrs of Pediatric and Adults
A Phase 1/2 study testing Spartalizumab in Pediatric cohort, Low-dose Pazopanib in Pediatric Cohort and Spartalizumab in Adult cohort in people with Refractory or Recurrent Solid Tumor, run by University Hospital, Bordeaux at 13 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Refractory or Recurrent Solid Tumor
- What is being tested?
- Spartalizumab in Pediatric cohort, Low-dose Pazopanib in Pediatric Cohort and Spartalizumab in Adult cohort
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 13 sitesFrance
- Study dates
- 17 May 2022to 17 Nov 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- For pediatric patients (Cohort 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).
- 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.
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- 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.
- Able to swallow tablets.
- Evaluable or measurable disease as defined by standard imaging criteria for the patient's tumor type (RECIST v1.1…).
- Life expectancy ≥ 3 months.
- 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.
- Able to comply with scheduled follow-up and with management of toxicity.
- 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.
- 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.
- Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
- For adults patients:
- Pre-screening phase:
- 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.
- 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.
- Evaluable or measurable disease as defined by standard imaging criteria for the patient's tumor type (RECIST v1.1…).
- Written informed consent from patient before any study-specific screening procedures are conducted according to local, regional or national guidelines.
- Screening phase (Cohort 2):
- 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
- Age ≥ 18 years at inclusion
- 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.
- Evaluable or measurable disease as defined by standard imaging criteria for the patient's tumor type (RECIST v1.1…).
- Life expectancy ≥ 3 months
- 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.
- 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.
- Written informed consent from patient before any study-specific screening procedures are conducted according to local, regional or national guidelines.
- Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
Who cannot join
- For pediatric and adult patients (Cohorts 1 and 2):
- 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).
- 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).
- 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).
- Uncontrolled hypertension
- Active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
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- Presence of any ≥ CTCAE grade 2 treatment-related toxicity with the exception of alopecia, ototoxicity or peripheral neuropathy.
- Systemic anticancer therapy within 21 days of the first study dose or 5 times its half-life, whichever is less.
- Previous myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks of the first study drug dose
- 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.
- Radiotherapy (non-palliative) within 21 days prior to the first dose of drug (or within 6 weeks for therapeutic doses of MIBG)
- 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.
- Currently taking medications with a known risk of prolonging the QT interval or inducing Torsades de Pointes
- High dose chemotherapy followed by peripheral stem cell transplantation within less than 6 months.
- 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.
- Diagnosis of prior or active autoimmune disease.
- Evidence of interstitial lung disease.
- 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.
- Known hypersensitivity to any study drug or component of the formulation.
- 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)
- Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study drug.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
France13 sites
CHU d'Angers - Unité d'Hématologie et d'Oncologie pédiatrique
Angers
CHU de Bordeaux - Unité d'Hématologie et d'Oncologie pédiatrique
Bordeaux, 33076
Institut Bergonié - Oncologie Médicale
Bordeaux, 33076
Centre Oscar Lambret - Oncologie pédiatrie
Lille, 59020
Oscar Lambret Center
Lille
Centre Léon Bérard - Oncologie Médicale
Lyon, 69373
Institut d'Hématologie et d'Oncologie Pédiatrique (IHOP) - Oncologie pédiatrique
Lyon, 69373
APHM Hôpital des Enfants La Timone - Hématologie Oncologie Pédiatrique
Marseille, 13385
Nantes University Hospital
Nantes
Institut Curie - Centre D'Oncologie SIREDO
Paris, 75005
Curie Institute
Paris
Strasbourg University Hospital
Strasbourg
Gustave Roussy - Oncologie pédiatrique
Villejuif, 94805
About this study
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.
Read more
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.
Read the detailed description
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. One hypothesis is that the tumor micro-environment (TME) - characterized by hypoxia, a low pH, and a high interstitial fluid pressure - can reduce the effectiveness of virtually all types of anticancer therapies, including immunotherapy. In adults, combination with other therapeutic modalities, including anti-angiogenic agents, is one of the many strategies currently under investigation to improve the response rates and duration of immunotherapies.
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. Therefore, such anti-angiogenic agents will likely need to be used in combination with various immunotherapeutic strategies that boost adaptive immune responses, such as those described in the next sections. For these reasons, the investigators proposed to combine immunotherapy and low dose of pazopanib to enhance the efficacy of immunotherapy in some selected pediatric patients and adults.
PDR001 (also referred to as spartalizumab) is a humanized monoclonal antibody (mAb) directed against human programmed death-1 (PD-1) that blocks the interaction between PD-1 and its ligands (PD-L1 and PD-L2).
Pazopanib is a potent, selective, oral, ATP competitive multitargeted receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, -2, and -3, c-kit, and platelet-derived growth factor receptors. It is approved by the US Food and Drug Administration for the treatment of advanced renal cell carcinoma and soft tissue sarcoma (STS) in adults. 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.
- Conditions
- Refractory or Recurrent Solid Tumor
- Being tested
- Spartalizumab in Pediatric cohort, Low-dose Pazopanib in Pediatric Cohort, Spartalizumab in Adult cohort, Low-dose Pazopanib in Adult Cohort
- Keywords
- refractory or recurrent solid tumor, immunotherapy, modulators of angiogenesis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Spartalizumab in Pediatric cohortDrug
Infusion of spartalizumab at four dose escalation levels: 2, 3, 4 and 6 mg/kg in successive cohorts of 3 patients, depending on the number of patients with dose-limiting toxicity (DLT) to maximum tolerated dose (MTD).
Low-dose Pazopanib in Pediatric CohortDrug
Oral pazopanib treatment at a fixed dose of 225mg/m²/day
Spartalizumab in Adult cohortDrug
Infusion of 400 mg of spartalizumab on Day1 of each cycle.
Low-dose Pazopanib in Adult CohortDrug
Oral pazopanib treatment with a fixed dose of 400 mg/day
| Study group | Role | What they receive |
|---|---|---|
| Pediatric cohort | Experimental | Multicentre, open-label, non-randomized, phase I clinical study, with dose-finding and expansion phases. Receives: Drug: Spartalizumab in Pediatric cohort; Drug: Low-dose Pazopanib in Pediatric Cohort |
| Adult cohort | Experimental | Multicenter phase II single-arm open-label clinical trial, with a pre-screening phase to identify patients with mature tertiary lymphoid structure (TLS). Receives: Drug: Spartalizumab in Adult cohort; Drug: Low-dose Pazopanib in Adult Cohort |
What is being measured
The primary outcome is the main question the study is designed to answer.
The maximum tolerated dose (MTD) in the pediatric cohort
The maximum tolerated dose (MTD) in the pediatric cohort will be defined as the dose closest to the target toxicity level of 25% of DLTs (Dose Limiting Toxicity) up to cycle 2 (8 weeks of treatment).
All patients will be evaluable for toxicity from the time of their first dose of study drug. All patients will be evaluable for DLT if they receive >75% of the planned dose after 2 cycles or if they have treatment-related toxicity at any time during the two cycles.
Measured: 2 months after inclusion ( treatment initiation)
6-month disease control rate in the adult cohort
The 6-month disease control rate is defined as the proportion of participants in complete response (CR), partial response (PR) or stable disease (SD) 6 months after treatment initiation.
All evaluable patients will be included in the response rate calculation. The subjects that will be assigned a response category are all patients who have received at least one treatment dose and have had their disease reevaluated. Objective tumor response will be measured according to RECIST 1.1 (Eisenhauer 2009) for solid tumor.
Measured: 6 months after inclusion ( treatment initiation)
Secondary outcomes (23)
Dose-limiting toxicity (DLT) in the pediatric cohort
A dose-limiting toxicity (DLT) is defined as a drug-related AE occurring in the first 8 weeks of study treatment.
DLT will be defined as follows:
- nausea, vomiting, alopecia, fever ≥ grade 3 lasting more than 72 hours
- fatigue ≥ grade 3 lasting more than one week
- other non-hematological toxicity ≥ grade 3
- laboratory abnormality ≥ grade 3 lasting > 10 days (except for hyperglycaemia and changes in serum electrolytes/enzymes without clinical impact)
- laboratory abnormality ≥ grade 4 (except for hyperglycaemia and changes in serum electrolytes/enzymes without clinical impact)
- febrile neutropenia (ANC<1000/mm3 with a single temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of >= 38degrees C (100.4 degrees F) for more than one hour)
- grade 4 neutropenia lasting ≥ 10 days
- grade 4 thrombocytopenia or grade 3 with bleeding requiring a platelet transfusion.
- amylase or lipase elevation grade 3 with symptom or sign on imagery of pancreatitis
Measured: 2 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 1 month after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 2 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 3 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 4 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 5 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 6 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 7 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 8 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 9 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 10 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 11 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Incidence of adverse events and serious adverse events, defined according to the NCI CTCAE v5.
Measured: 12 months after inclusion ( treatment initiation)
Overall Response Rate in pediatric and adult cohorts
The best overall response is the best response (CR or PR) recorded from the start of the treatment until patients get off-study or the cut-off date, whichever comes first.
Measured: 12 months after inclusion ( treatment initiation)
Progression-free survival in pediatric and adult cohorts
duration from start of the treatment to disease progression (clinically or radiologically) or death (regardless of cause of death), whichever comes first. Patients alive and free of progression at the cut-off date will be censored at the last assessment date.
Measured: 12 months after inclusion ( treatment initiation)
Overall survival in pediatric and adult cohorts
duration from start of the treatment to death (regardless of cause of death). Patients alive at the cut-off date will be censored at the last assessment date
Measured: 12 months after inclusion ( treatment initiation)
Response duration in pediatric and adult cohorts
Response duration will be measured from the time measurement criteria for CR/PR are first met until the first date that recurrent or progressive disease is objectively documented or death, whichever occurs earlier. Duration of response for patients free of progression at the cut-off date will be censored at the last imaging response-scan date.
Measured: 12 months after inclusion ( treatment initiation)
Response rate in pediatric and adult cohorts
The subjects that will be assigned a response category are all patients who have received at least one treatment dose and have had their disease reevaluated. Objective tumor response will be measured according to RECIST 1.1 (Eisenhauer 2009) for solid tumor.
Measured: 2 months after inclusion ( treatment initiation)
Response rate in pediatric and adult cohorts
The subjects that will be assigned a response category are all patients who have received at least one treatment dose and have had their disease reevaluated. Objective tumor response will be measured according to RECIST 1.1 (Eisenhauer 2009) for solid tumor.
Measured: 4 months after inclusion ( treatment initiation)
Response rate in pediatric and adult cohorts
The subjects that will be assigned a response category are all patients who have received at least one treatment dose and have had their disease reevaluated. Objective tumor response will be measured according to RECIST 1.1 (Eisenhauer 2009) for solid tumor.
Measured: 8 months after inclusion ( treatment initiation)
Response rate in pediatric and adult cohorts
The subjects that will be assigned a response category are all patients who have received at least one treatment dose and have had their disease reevaluated. Objective tumor response will be measured according to RECIST 1.1 (Eisenhauer 2009) for solid tumor.
Measured: 10 months after inclusion ( treatment initiation)
Response rate in pediatric and adult cohorts
The subjects that will be assigned a response category are all patients who have received at least one treatment dose and have had their disease reevaluated. Objective tumor response will be measured according to RECIST 1.1 (Eisenhauer 2009) for solid tumor.
Measured: 12 months after inclusion ( treatment initiation)
Response rate in pediatric cohort
The subjects that will be assigned a response category are all patients who have received at least one treatment dose and have had their disease reevaluated. Objective tumor response will be measured according to RECIST 1.1 (Eisenhauer 2009) for solid tumor.
Measured: 6 months after inclusion ( treatment initiation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2022
- Study start17 May 2022
- Primary completion26 Aug 2025
- Study completion17 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory or Recurrent Solid TumorStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Pediatric cohort: Multicentre, open-label, non-randomized, phase I clinical study, with dose-finding and expansion phases. Adult cohort: Multicenter phase II single-arm open-label clinical trial, with a pre-screening phase to identify patients with mature tertiary lymphoid structure (TLS).
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute, France, Fondation ARC, Novartis
- Responsible party
- Sponsor
- Investigators
- Stéphane DUCASSOU, MD, PhD, Principal investigator, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05210413
- Sponsor's protocol ID
- CHUBX 2020/31
- Acronym
- SPARTO
- Status last verified
- Jan 2026
- First submitted
- 13 Jan 2022
- Last updated
- 15 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Spartalizumab and Low-dose PAzopanib in Refractory or Relapsed Solid TumOrs of Pediatric and Adults
- ClinicalTrials.gov ID
- NCT05210413
- Acronym / sponsor ID
- SPARTO / CHUBX 2020/31
- Conditions
- Refractory or Recurrent Solid Tumor
- Keywords
- refractory or recurrent solid tumor, immunotherapy, modulators of angiogenesis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Collaborators
- National Cancer Institute, France, Fondation ARC, Novartis
- Study start
- 17 May 2022 (actual)
- Primary completion
- 26 Aug 2025 (actual)
- Study completion
- 17 Nov 2027 (estimated)
- First posted
- 27 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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. One hypothesis is that the tumor micro-environment (TME) - characterized by hypoxia, a low pH, and a high interstitial fluid pressure - can reduce the effectiveness of virtually all types of anticancer therapies, including immunotherapy. In adults, combination with other therapeutic modalities, including anti-angiogenic agents, is one of the many strategies currently under investigation to improve the response rates and duration of immunotherapies.
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. Therefore, such anti-angiogenic agents will likely need to be used in combination with various immunotherapeutic strategies that boost adaptive immune responses, such as those described in the next sections. For these reasons, the investigators proposed to combine immunotherapy and low dose of pazopanib to enhance the efficacy of immunotherapy in some selected pediatric patients and adults.
PDR001 (also referred to as spartalizumab) is a humanized monoclonal antibody (mAb) directed against human programmed death-1 (PD-1) that blocks the interaction between PD-1 and its ligands (PD-L1 and PD-L2).
Pazopanib is a potent, selective, oral, ATP competitive multitargeted receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, -2, and -3, c-kit, and platelet-derived growth factor receptors. It is approved by the US Food and Drug Administration for the treatment of advanced renal cell carcinoma and soft tissue sarcoma (STS) in adults. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Pediatric cohort: Multicentre, open-label, non-randomized, phase I clinical study, with dose-finding and expansion phases. Adult cohort: Multicenter phase II single-arm open-label clinical trial, with a pre-screening phase to identify patients with mature tertiary lymphoid structure (TLS).
| Arm | Type | Receives |
|---|---|---|
| Pediatric cohort | Experimental | Drug: Spartalizumab in Pediatric cohort, Drug: Low-dose Pazopanib in Pediatric CohortMulticentre, open-label, non-randomized, phase I clinical study, with dose-finding and expansion phases. |
| Adult cohort | Experimental | Drug: Spartalizumab in Adult cohort, Drug: Low-dose Pazopanib in Adult CohortMulticenter phase II single-arm open-label clinical trial, with a pre-screening phase to identify patients with mature tertiary lymphoid structure (TLS). |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (37 listed)
- For pediatric patients (Cohort 1):
- For adults patients:
Key exclusion criteria (21 listed)
- 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).
- 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).
- 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).
- Uncontrolled hypertension
- Active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Spartalizumab in Pediatric cohortInfusion of spartalizumab at four dose escalation levels: 2, 3, 4 and 6 mg/kg in successive cohorts of 3 patients, depending on the number of patients with dose-limiting toxicity (DLT) to maximum tolerated dose (MTD). | Drug | Pediatric cohort |
| Low-dose Pazopanib in Pediatric CohortOral pazopanib treatment at a fixed dose of 225mg/m²/day | Drug | Pediatric cohort |
| Spartalizumab in Adult cohortInfusion of 400 mg of spartalizumab on Day1 of each cycle. | Drug | Adult cohort |
| Low-dose Pazopanib in Adult CohortOral pazopanib treatment with a fixed dose of 400 mg/day | Drug | Adult cohort |
Primary outcome
The maximum tolerated dose (MTD) in the pediatric cohort
Time frame: 2 months after inclusion ( treatment initiation)
The maximum tolerated dose (MTD) in the pediatric cohort will be defined as the dose closest to the target toxicity level of 25% of DLTs (Dose Limiting Toxicity) up to cycle 2 (8 weeks of treatment). All patients will be evaluable for toxicity from the time of their first dose of study drug. All patients will be evaluable for DLT if they receive >75% of the planned dose after 2 cycles or if they have treatment-related toxicity at any time during the two cycles.
6-month disease control rate in the adult cohort
Time frame: 6 months after inclusion ( treatment initiation)
The 6-month disease control rate is defined as the proportion of participants in complete response (CR), partial response (PR) or stable disease (SD) 6 months after treatment initiation. All evaluable patients will be included in the response rate calculation. The subjects that will be assigned a response category are all patients who have received at least one treatment dose and have had their disease reevaluated. Objective tumor response will be measured according to RECIST 1.1 (Eisenhauer 2009) for solid tumor.
23 secondary outcomes
Dose-limiting toxicity (DLT) in the pediatric cohort
Time frame: 2 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] in pediatric and adult cohorts
Time frame: 1 month after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Time frame: 2 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Time frame: 3 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Time frame: 4 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Time frame: 5 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Time frame: 6 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Time frame: 7 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Time frame: 8 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Time frame: 9 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Time frame: 10 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Time frame: 11 months after inclusion ( treatment initiation)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts
Time frame: 12 months after inclusion ( treatment initiation)
Overall Response Rate in pediatric and adult cohorts
Time frame: 12 months after inclusion ( treatment initiation)
Progression-free survival in pediatric and adult cohorts
Time frame: 12 months after inclusion ( treatment initiation)
Overall survival in pediatric and adult cohorts
Time frame: 12 months after inclusion ( treatment initiation)
Response duration in pediatric and adult cohorts
Time frame: 12 months after inclusion ( treatment initiation)
Response rate in pediatric and adult cohorts
Time frame: 2 months after inclusion ( treatment initiation)
Response rate in pediatric and adult cohorts
Time frame: 4 months after inclusion ( treatment initiation)
Response rate in pediatric and adult cohorts
Time frame: 8 months after inclusion ( treatment initiation)
Response rate in pediatric and adult cohorts
Time frame: 10 months after inclusion ( treatment initiation)
Response rate in pediatric and adult cohorts
Time frame: 12 months after inclusion ( treatment initiation)
Response rate in pediatric cohort
Time frame: 6 months after inclusion ( treatment initiation)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stéphane DUCASSOU, MD, PhD principal investigator
University Hospital, Bordeaux
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Spartalizumab in Pediatric cohort, Low-dose Pazopanib in Pediatric Cohort and Spartalizumab in Adult cohort in people with Refractory or Recurrent Solid Tumor, run by University Hospital, Bordeaux at 13 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 37 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The maximum tolerated dose (MTD) in the pediatric cohort (time frame: 2 months after inclusion ( treatment initiation)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2026.