Spartalizumab and Low-dose PAzopanib in Refractory or Relapsed Solid TumOrs of Pediatric and Adults (NCT05210413) | Clinical Trial Compass
Active — Not RecruitingPhase 1/2
Spartalizumab and Low-dose PAzopanib in Refractory or Relapsed Solid TumOrs of Pediatric and Adults
France80 participantsStarted 2022-05-17
Plain-language 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.
Who can participate
Age range5 Years
SexALL
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Inclusion criteria
✓. For pediatric patients (Cohort 1):
✓. Patients should be without standard established therapeutic alternatives at the time of enrollment suffering from the following conditions :
✓. 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.
✓. 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:
Exclusion criteria
What they're measuring
1
The maximum tolerated dose (MTD) in the pediatric cohort
Timeframe: 2 months after inclusion ( treatment initiation)
2
6-month disease control rate in the adult cohort
Timeframe: 6 months after inclusion ( treatment initiation)
. 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.
✕. 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