Spartalizumab and Low-dose PAzopanib in Refractory or Relapsed Solid TumOrs of Pediatric and Adults

NCT05210413 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: CHUBX 2020/31
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 13

Brief 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. 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.

Conditions

Refractory or Recurrent Solid Tumor

Keywords

refractory or recurrent solid tumor; immunotherapy; modulators of angiogenesis

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  6 months after inclusion ( treatment initiation)

Secondary Outcomes (23)

• Dose-limiting toxicity (DLT) in the pediatric cohort

  2 months after inclusion ( treatment initiation)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] in pediatric and adult cohorts

  1 month after inclusion ( treatment initiation)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts

  2 months after inclusion ( treatment initiation)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts

  3 months after inclusion ( treatment initiation)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]in pediatric and adult cohorts

  4 months after inclusion ( treatment initiation)

Study Arms (2)

Pediatric cohort

EXPERIMENTAL

Multicentre, open-label, non-randomized, phase I clinical study, with dose-finding and expansion phases.

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).

Drug: Spartalizumab in Adult cohort; Drug: Low-dose Pazopanib in Adult Cohort

Interventions

Spartalizumab in Pediatric cohort DRUG

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).

Pediatric cohort

Low-dose Pazopanib in Pediatric Cohort DRUG

Oral pazopanib treatment at a fixed dose of 225mg/m²/day

Pediatric cohort

Spartalizumab in Adult cohort DRUG

Infusion of 400 mg of spartalizumab on Day1 of each cycle.

Adult cohort

Low-dose Pazopanib in Adult Cohort DRUG

Oral pazopanib treatment with a fixed dose of 400 mg/day

Adult cohort

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• For pediatric and adult patients (Cohorts 1 and 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).
• 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.
• 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.

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• National Cancer Institute, France: collaborator
• Fondation ARC: collaborator
• Novartis: collaborator

Study Sites (13)

CHU d'Angers - Unité d'Hématologie et d'Oncologie pédiatrique

Angers, France

Location

CHU de Bordeaux - Unité d'Hématologie et d'Oncologie pédiatrique

Bordeaux, 33076, France

Location

Institut Bergonié - Oncologie Médicale

Bordeaux, 33076, France

Location

Centre Oscar Lambret - Oncologie pédiatrie

Lille, 59020, France

Location

Oscar Lambret Center

Lille, France

Location

Centre Léon Bérard - Oncologie Médicale

Lyon, 69373, France

Location

Institut d'Hématologie et d'Oncologie Pédiatrique (IHOP) - Oncologie pédiatrique

Lyon, 69373, France

Location

APHM Hôpital des Enfants La Timone - Hématologie Oncologie Pédiatrique

Marseille, 13385, France

Location

Nantes University Hospital

Nantes, France

Location

Institut Curie - Centre D'Oncologie SIREDO

Paris, 75005, France

Location

Curie Institute

Paris, France

Location

Strasbourg University Hospital

Strasbourg, France

Location

Gustave Roussy - Oncologie pédiatrique

Villejuif, 94805, France

Location

MeSH Terms

Interventions

spartalizumab; pazopanib

Study Officials

• Stéphane DUCASSOU, MD, PhD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: January 27, 2022
• Study Start: May 17, 2022
• Primary Completion: August 26, 2025
• Study Completion (Estimated): November 17, 2027
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (13)