Safety and Efficacy of Cyclophosphamide, Sorafenib, Bevacizumab, and Atezolizumab in Pediatric Solid Tumor Patients
Status:
Recruiting
Trial end date:
2037-06-01
Target enrollment:
Participant gender:
Summary
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 hepatocellular carcinoma (HCC) 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
HCC 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 HCC 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
fibrolamellar carcinoma, 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 HCC, DSRCT, MRT, FL-HCC and other rare solid tumors