Safety and Efficacy of Cyclophosphamide, Sorafenib, Bevacizumab, and Atezolizumab in Pediatric Solid Tumor Patients

Conditions

• Fibrolamellar Carcinoma
• Hepatocellular Carcinoma
• Malignant Solid Tumor
• Pediatric Cancer
• Pediatric Solid Tumor
• Refractory Solid Tumor

Eligibility Criteria

Sex

ALL

Age

N/A - 30 Years

Healthy Volunteers

Not accepted

Interventions

• Atezolizumab — DRUG
  Atezolizumab intravenously, every 3 weeks, Day 1
• Sorafenib — DRUG
  Sorafenib by mouth every 12 hours, Days 1-21
• Bevacizumab — DRUG
  Bevacizumab intravenously, every 3 weeks, Day 1
• Cyclophosphamide — DRUG
  Low-dose cyclophosphamide by mouth once daily, Days 1-21

Study Details

This is a phase I/II study to evaluate the safety of combining intravenous (IV) atezolizumab and bevacizumab every three weeks, with daily oral cyclophosphamide and pharmacokinetic (PK)-guided sorafenib in children and adolescent and young adults (AYA) with relapsed or refractory solid malignancies (Part 1), and then evaluate the response rate of this combination in children, AYA with relapsed or refractory fibrolamellar carcinoma (FLC) and other rare solid malignancies (Part 2). Primary Objectives Part 1 * To establish the safety associated with the administration of the combination of cyclophosphamide, PK-guided sorafenib, bevacizumab and atezolizumab in children and AYA with relapsed or refractory solid tumors * To determine if sorafenib systemic exposure can be successfully targeted to an AUC between 20 and 55 hr·µg/mL by Day 21 of cycle 1 in 60% of evaluable patients, when given in combination with cyclophosphamide, bevacizumab, and atezolizumab in children and AYA with relapsed or refractory solid tumors Part 2 * To evaluate the response rate (CR+PR) of the combination of cyclophosphamide, PK-guided sorafenib, bevacizumab and atezolizumab in children and AYA with relapsed or refractory FLC following two cycles of therapy * To determine if the use of PK-guided sorafenib dosing to maintain a systemic exposure between 20 and 55 reduces the interpatient pharmacokinetic variability of sorafenib and the incidence of sorafenib- induced skin toxicities in children and AYA with relapsed or refractory FLC and other rare solid tumors Parts 1 \& 2 * To determine if the combination of cyclophosphamide, PK-guided sorafenib and atezolizumab will result in increased intratumoral T-cell infiltration of CD8+C45RO+ cells between baseline and following two courses of therapy in pediatric children and AYA with relapsed or refractory solid tumors following two cycles of therapy * To characterize the pharmacokinetics of atezolizumab in combination with cyclophosphamide, PK-guided sorafenib and bevacizumab in children and AYA with relapsed or refractory solid tumors * To assess the feasibility of performing contrast enhanced ultrasound and explore the correlation between quantitative CEUS parameters and clinical response. Secondary Objectives Part 1 • To describe the response rate (CR+PR) of the combination of cyclophosphamide, PK-guided sorafenib, bevacizumab and atezolizumab in children and AYA with relapsed or refractory solid tumors following two cycles of therapy Part 2 • To describe the response rate (CR+PR) of the combination of cyclophosphamide, PK-guided sorafenib, bevacizumab and atezolizumab in children and AYA with relapsed or refractory FLC, HCC, desmoplastic small round cell tumor, malignant rhabdoid tumor, and other rare solid tumors following two cycles of therapy Parts 1\&2 * To describe the number of children with liver tumors, initially judged unresectable at diagnosis, that can have their primary tumor resected after treatment with oral cyclophosphamide and sorafenib with intravenous bevacizumab and atezolizumab * To describe changes in immune cells in the peripheral blood at periodic times before and after treatment with this combination chemoimmunotherapy * To describe the PFS, EFS, and OS in patients treated with the combination of cyclophosphamide, PK-guided sorafenib, bevacizumab, and atezolizumab in patients with relapsed or refractory FLC, DSRCT, MRT, HCC and other rare solid tumors

Key Dates

Start date

Nov 7, 2022

Status verified

May 2026

Primary completion

Jun 30, 2032

Completion

Jun 30, 2037

Study Design

Enrollment

64 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Other: Treatment
  All participants will receive Atezolizumab, Bevacizumab,Sorafenib and cyclophosphamide until maximum tolerated dose is reached.Tolerability will be defined after completion of Course 1. Part 2 will begin once the recommended phase 2 dose (RP2D) is determined.

Primary Outcome Measure

Part 1: Recommended phase 2 doses (RP2Ds) [ Time Frame: At the end of cycle 2 (each cycle is 21 days)] ]

Central Contacts

• Jessica Gartrell, MD
  888-226-4343
  [email protected]

Locations (2)

Find similar trials in Germantown, TN

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