Refractory Solid TumorPhase 1/2NCT05468359

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

A Phase 1/2 study testing Atezolizumab, Sorafenib and Bevacizumab in people with Refractory Solid Tumor and Hepatocellular Carcinoma, run by St. Jude Children's Research Hospital at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial 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… Read more about this study

Who is it for?: Ages Up to 30 years
Conditions the study is for: Refractory Solid Tumor, Hepatocellular Carcinoma, Malignant Solid Tumor
What is being tested?: Atezolizumab, Sorafenib and Bevacizumab
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 64 participants
Where: 2 sitesUnited States
Study dates: 7 Nov 2022to Jun 2037
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 Up to 30 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Age: Patients must be < 30 years at the time of enrollment on study.
Willingness to enroll on the St. Jude Molecular Analysis of Solid Tumors (MAST) study.
Diagnosis
Part 1: Patients with refractory or recurrent (relapsed) solid tumors accessible by biopsy for which there is no standard therapy are eligible.
Part 2: Patients with one of the following diagnoses:
Biopsy accessible refractory or recurrent (relapsed) hepatocellular carcinoma

Show all 31Show fewer

Biopsy accessible refractory or recurrent (relapsed)or FL-HCC, DSRCT or non-CNS MRT.
Performance level: Karnofsky > 50 for patients > 16 years of age and Lansky > 50 for patients < 16 years of age (See Appendix III). Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Disease status: Patients must tumors that are unresectable and have either measurable or evaluable disease that is accessible by biopsy
Organ function: Must have adequate organ and bone marrow function as defined by the following parameters:
Patients with solid tumor not metastatic to bone marrow:
Peripheral absolute neutrophil count (ANC) >1,000/mm3
Platelet count > 75,000/mm3 (no transfusion within 7 days of enrollment)
Hemoglobin > 8 g/dL (with or without support)
Patients with solid tumor metastatic to bone marrow will be eligible for study but not evaluable for hematologic toxicity. These patients must not be known to be refractory to red cell or platelet transfusions. At least 2 of every cohort of 3 patients must be evaluable for hematologic toxicity. If dose limiting hematologic toxicity is observed at any dose level, all subsequent patients enrolled must be evaluable for hematologic toxicity.
Adequate renal function defined as serum creatinine based on age as shown in Table 1, or creatinine clearance or radioisotope GFR 50 ml/min/1.73m2 (GFR 40 ml/min/1.73m2 if < 2 years of age).
Adequate hepatic function defined as total bilirubin < 5x upper limit of normal (ULN) and AST/ALT < 3 x ULN for age.
Adequate cardiac function defined as shortening fraction > 28% OR ejection fraction of ≥ 47% by echocardiogram.
Adequate blood clotting defined as PT/PTT < 1.2 x ULN without factor replacement products for 7 days
Females of childbearing potential and males able to father a child must be willing to practice acceptable methods of birth control to prevent pregnancy during the study and for at least 5 months after last dose of therapy.
Patients must have fully recovered from the acute toxic effects of chemotherapy, immunotherapy, surgery, or radiotherapy prior to entering this study:
Myelosuppressive chemotherapy: Patient has not received myelosuppressive chemotherapy within 1 weeks of enrollment onto this study (within 2 weeks of estimated therapy start date) (4 weeks if prior nitrosourea).
Hematopoietic growth factors: At least 7 days must have elapsed since the completion of therapy with a growth factor. At least 14 days must have elapsed after receiving pegfilgrastim.
Biologic (anti-neoplastic agent): At least 7 days must have elapsed since completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur.
Monoclonal antibodies: At least 14 days (at least 21 days from therapy start date) must have elapsed since the completion of therapy with a monoclonal antibody.
Radiotherapy: At least 1 week (2 weeks from estimated therapy start date) must have elapsed since any irradiation; at least 5 weeks (at least 6 weeks from estimated therapy start date) must have elapsed since craniospinal RT or substantial bone marrow irradiation.
Chemoembolization: at least 21 days (28 days from estimated therapy start date) must have elapsed since the completion of chemoembolization
Radioembolization: at least 21 days (28 days from estimated therapy start date) must have elapsed since the completion of radioembolization
Cardiac disease or hypertension: Patients must not have a history of myocardial - infarction, severe or unstable angina, or severe peripheral vascular disease. Hypertension must be well controlled on stable doses of medication for at least two weeks.
Female participant who is post-monarchal must have a negative urine or serum pregnancy test.
Life expectancy of at least 8 weeks

Who cannot join

Pregnant or breastfeeding.
Currently receiving other investigational drugs.
Unwilling or unable to comply with the safety monitoring requirements of this protocol.
Tumor not safely accessible by biopsy
Inability or unwillingness of research participant or legal guardian / representative to give written informed consent.
Surgical procedures and serious or non-healing wounds: patients with a documented, chronic non-healing wound, ulcer, or bone fracture or history of a major surgical procedure or significant traumatic injury within 28 days prior to beginning therapy are excluded due to preclinical evidence supporting the potential for delayed wound healing.
Minor surgical procedures for minimally invasive biopsies will be allowed. For minor surgeries, the wound must be healed, and 7 days elapsed since surgery. For procedures such as the placement of an indwelling IV catheter, it is recommended that bevacizumab be postponed for at least 24 hours after the procedure.
Thrombosis: Patients must not have a deep venous or arterial thrombosis (including pulmonary embolism) within the last three months prior to study entry and must not have a known thrombophilic condition (i.e., protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome).

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Jessica Gartrell, MD contact

888-226-4343

referralino@stjude.org

United States2 sites, 1 recruiting

Methodist Le Bonheur Healthcare
Germantown, Tennessee, 38138
Withdrawn
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Jessica Gartrell, MD, 888-226-4343, referralino@stjude.org
Jessica Gartrell, MD
Recruiting

Other trials in United States

About this study

Official title: ANGIO-A: Safety and Tolerability of Oral Cyclophosphamide and Sorafenib With Intravenous Bevacizumab With the Addition of Atezolizumab in Pediatric Solid Tumor Patients

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

Read the detailed description

Exploratory Objectives (Parts 1 \& 2)

To determine the number of HCC and FLC xenografts that can be successfully established from children with relapsed or refractory disease (enrollment on MAST with biopsy for fresh tissue required)
To evaluate the immune cell infiltrates in children with relapsed or refractory solid tumors before and after two cycles of cyclophosphamide, sorafenib, bevacizumab and atezolizumab
To evaluate the number, type, specificity, repertoire, and activity of intratumoral T cells after two cycles of therapy, compared to baseline
To characterize changes in tumor associated macrophages (polarization) between baseline and after two cycles of cyclophosphamide, sorafenib, bevacizumab and atezolizumab
To measure changes in tumor mutational burden and mutation heterogeneity
To explore associations between T stem cell epigenetic signatures and response to treatment
To explore the association between baseline CD45RO+/CD8+ T-cell infiltration and PD-L1 expression and response to treatment
To characterize tumor heterogeneity and microenvironment using single-cell/nuclear RNA sequencing pre- and post-treatment
To longitudinally assess and quantify numerous metrics of quality of life (QoL), family distress and functional impairment for patients enrolled on ANGIOA and their primary caretakers
To qualitatively assess patient and family physical, emotional and psychosocial experiences prior to and after receipt of therapy on ANGIOA through semi-structured interviews
To assess the acceptability and feasibility of capturing patient/caregiver interview data at the time of enrollment and discontinuation on ANGIOA
To assess the feasibility of performing quantitative multiparametric mapping sequences in patients already undergoing MRI for staging purposes and explore the correlation between quantitative enhancement and other parameters and clinical response

Part 1 (safety/tolerability): Children with relapsed or refractory solid tumors with biopsy accessible and evaluable disease will be treated with two courses of oral PK-guided sorafenib (starting area under the curve (AUC) target: 20-55 ug/ml/hr), oral cyclophosphamide (50 mg/m2/dose, daily (qd) x 21 days), IV bevacizumab (15 mg/kg/dose, every (q) 21 days) and IV atezolizumab (15 mg/kg [max dose 1200 mg] q 21 days). Tumor biopsies are required before starting treatment and after course two (Section 4.1). Biopsied tissue will be used for enrollment on MAST and to evaluate changes in T-cell infiltration. Sorafenib PK will be obtained and dose adjusted to target an AUC between 20 and 55 hr·µg/mL by Day 21 of C1. Tolerability will be defined after completion of Course 1. Part 2 will begin once the recommended phase 2 dose (RP2D) is determined.

Part 2 (efficacy): Children and AYA with relapsed or refractory FLC will be treated with two courses of oral cyclophosphamide and sorafenib with IV bevacizumab and atezolizumab based on the RP2D from Part 1. Tumor response will be assessed after two courses according to immunologic and imaging criteria (Section 4.1). Eligible patients with hepatocellular (HCC), desmoplastic small round cell tumor (DSRCT) or non-central nervous system (CNS) malignant rhabdoid tumors (MRT) will be enrolled on separate strata but target accrual will be determined by patients with FLC.

Conditions: Refractory Solid Tumor, Hepatocellular Carcinoma, Malignant Solid Tumor, Pediatric Cancer, Pediatric Solid Tumor, Fibrolamellar Carcinoma
Being tested: Atezolizumab, Sorafenib, Bevacizumab, Cyclophosphamide
Medical subject headings: Carcinoma, Hepatocellular, Neoplasms, Fibrolamellar hepatocellular carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AtezolizumabDrug
Also called TECENTRIQ®
Atezolizumab intravenously, every 3 weeks, Day 1
SorafenibDrug
Also called BAY-43-9006, Nexavar(R)
Sorafenib by mouth every 12 hours, Days 1-21
BevacizumabDrug
Also called rhuMab VEGF, Avastin(R)
Bevacizumab intravenously, every 3 weeks, Day 1
CyclophosphamideDrug
Also called Cytoxan(R)
Low-dose cyclophosphamide by mouth once daily, Days 1-21

Study groups in NCT05468359
Study group	Role	What they receive
Treatment	Other	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. Receives: Drug: Atezolizumab; Drug: Sorafenib; Drug: Bevacizumab; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1: Recommended phase 2 doses (RP2Ds)
The number of participants who develop a dose limiting toxicity within the first two cycles of therapy that are at least possibly, probably or definitely attributable to atezolizumab, bevacizumab, sorafenib or cyclophosphamide.
Measured: At the end of cycle 2 (each cycle is 21 days)]
PK measures of Sorafenib
The number of participants exhibiting a sorafenib exposure (steady-state AUC0-12h) between 20 and 55 hr·µg/mL by Day 21 of cycle 1.
Measured: At the end of cycle 1 (each cycle is 21 days)]
Part 2: Response rate
The number of participants with relapsed or refractory HCC whose tumors show a response (CR+PR) after 2 cycles of cyclophosphamide, PK-guided sorafenib, bevacizumab and atezolizumab
Measured: At the end of cycle 2 (each cycle is 21 days)]
PK measure of sorafenib
The number of participants who have a sorafenib systemic exposure between 20 and 55 who experience sorafenib-induced skin toxicity compared to the number of participants who have a systemic sorafenib exposure outside of the 20-55 range who experience sorafenib-induced skin toxicity.
Measured: At the end of cycle 1 (each cycle is 21 days)]
Parts 1 & 2: Intratumoral T-cell infiltration of CD8+C45RO+ cells
The number of participants whose tumors show an increase in the ratio of CD45RO+/CD3+ T cells of at least 27% OR who show an absolute increase in CD3+ cells from baseline to the end of cycle 2 (approximately 42 days from the start of therapy).
Measured: At the end of cycle 2 (each cycle is 21 days)]

Secondary outcomes (7)

Part 1:Response rate of relapsed or refractory solid tumors
The number of participants with relapsed or refractory solid tumors whose tumors have a response (CR or PR) after two cycles of the combination of cyclophosphamide, PK-guided sorafenib, bevacizumab and atezolizumab.
Measured: At the end of cycle 2 (each cycle is 21 days)]
Part 2: Response rate of relapsed or refractory fibrolamellar carcinoma, desmoplastic small round cell tumor, malignant rhabdoid tumor
The number of participants with relapsed or refractory fibrolamellar carcinoma, desmoplastic small round cell tumor, malignant rhabdoid tumor, and other rare solid tumors whose tumors have a response (CR or PR) after two cycles of the combination of cyclophosphamide, PK-guided sorafenib, bevacizumab and atezolizumab.
Measured: At the end of cycle 2 (each cycle is 21 days)]
Resection rate of liver tumors
The number of participants with liver tumors, initially judged relapsed or refractory at diagnosis, that can have their primary tumor resected after treatment with oral cyclophosphamide and sorafenib with intravenous bevacizumab and atezolizumab.
Measured: At the end of cycle 1 (each cycle is 21 days)]
Progression Free Survival
The PFS of 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.
Measured: At the end of cycle 2 (each cycle is 21 days
Event Free Survival
The EFS of 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.
Measured: At the end of cycle 2 (each cycle is 21 days
Overall Survival
The EFS of 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.
Measured: At the end of cycle 2 (each cycle is 21 days
Systemic immune activation correlation with tumor response
The number of participants who show an activated systemic T-cell response and who have a CR or PR after two courses of cyclophosphamide, PK-guided sorafenib, bevacizumab, and atezolizumab.
Measured: after 2 courses of therapy (each cycle is 21 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Nov 2022Jun 2037

First posted21 Jul 2022
Study start7 Nov 2022
Primary completionJun 2032 (estimated)
Study completionJun 2037 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Refractory Solid TumorStudies of the same condition, open and under way.
More trials run by St. Jude Children's Research HospitalThe 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 64 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05468359
Sponsor's protocol ID: ANGIO-A
Status last verified: May 2026
First submitted: 13 Jun 2022
Last updated: 19 May 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

Interested in taking part?

Jessica Gartrell, MD

888-226-4343

referralino@stjude.org

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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All Refractory Solid Tumor trials

Study at a glance

From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: ANGIO-A: Safety and Tolerability of Oral Cyclophosphamide and Sorafenib With Intravenous Bevacizumab With the Addition of Atezolizumab in Pediatric Solid Tumor Patients
ClinicalTrials.gov ID: NCT05468359
Acronym / sponsor ID: ANGIO-A
Conditions: Refractory Solid Tumor, Hepatocellular Carcinoma, Malignant Solid Tumor, Pediatric Cancer, Pediatric Solid Tumor, Fibrolamellar Carcinoma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 64 participants (estimated)
Lead sponsor: St. Jude Children's Research HospitalUniversity, hospital or other
Study start: 7 Nov 2022 (actual)
Primary completion: Jun 2032 (estimated)
Study completion: Jun 2037 (estimated)
First posted: 21 Jul 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.

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

Detailed description

Exploratory Objectives (Parts 1 \& 2)

To determine the number of HCC and FLC xenografts that can be successfully established from children with relapsed or refractory disease (enrollment on MAST with biopsy for fresh tissue required)
To evaluate the immune cell infiltrates in children with relapsed or refractory solid tumors before and after two cycles of cyclophosphamide, sorafenib, bevacizumab and atezolizumab
To evaluate the number, type, specificity, repertoire, and activity of intratumoral T cells after two cycles of therapy, compared to baseline
To characterize changes in tumor associated macrophages (polarization) between baseline and after two cycles of cyclophosphamide, sorafenib, bevacizumab and atezolizumab
To measure changes in tumor mutational burden and mutation heterogeneity
To explore associations between T stem cell epigenetic signatures and response to treatment
To explore the association between baseline CD45RO+/CD8+ T-cell infiltration and PD-L1 expression and response to treatment
To characterize tumor heterogeneity and microenvironment using single-cell/nuclear RNA sequencing pre- and post-treatment
To longitudinally assess and quantify numerous metrics of quality of life (QoL), family distress and functional impairment for patients enrolled on ANGIOA and their primary caretakers
To qualitatively assess patient and family physical, emotional and psychosocial experiences prior to and after receipt of therapy on ANGIOA through semi-structured interviews
To assess the acceptability and feasibility of capturing patient/caregiver interview data at the time of enrollment and discontinuation on ANGIOA
To assess the feasibility of performing quantitative multiparametric mapping sequences in patients already undergoing MRI for staging purposes and explore the correlation between quantitative enhancement and other parameters and clinical response

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment	Other	Drug: Atezolizumab, Drug: Sorafenib, Drug: Bevacizumab, Drug: CyclophosphamideAll 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.

Who may qualify

Ages: Up to 30 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (31 listed)

Age: Patients must be < 30 years at the time of enrollment on study.
Willingness to enroll on the St. Jude Molecular Analysis of Solid Tumors (MAST) study.
Diagnosis
Part 1: Patients with refractory or recurrent (relapsed) solid tumors accessible by biopsy for which there is no standard therapy are eligible.
Part 2: Patients with one of the following diagnoses:

Key exclusion criteria (8 listed)

Pregnant or breastfeeding.
Currently receiving other investigational drugs.
Unwilling or unable to comply with the safety monitoring requirements of this protocol.
Tumor not safely accessible by biopsy
Inability or unwillingness of research participant or legal guardian / representative to give written informed consent.

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
AtezolizumabAlso: TECENTRIQ®Atezolizumab intravenously, every 3 weeks, Day 1	Drug	Treatment
SorafenibAlso: BAY-43-9006, Nexavar(R)Sorafenib by mouth every 12 hours, Days 1-21	Drug	Treatment
BevacizumabAlso: rhuMab VEGF, Avastin(R)Bevacizumab intravenously, every 3 weeks, Day 1	Drug	Treatment
CyclophosphamideAlso: Cytoxan(R)Low-dose cyclophosphamide by mouth once daily, Days 1-21	Drug	Treatment

Primary outcome

Part 1: Recommended phase 2 doses (RP2Ds)
Time frame: At the end of cycle 2 (each cycle is 21 days)]
The number of participants who develop a dose limiting toxicity within the first two cycles of therapy that are at least possibly, probably or definitely attributable to atezolizumab, bevacizumab, sorafenib or cyclophosphamide.
PK measures of Sorafenib
Time frame: At the end of cycle 1 (each cycle is 21 days)]
The number of participants exhibiting a sorafenib exposure (steady-state AUC0-12h) between 20 and 55 hr·µg/mL by Day 21 of cycle 1.
Part 2: Response rate
Time frame: At the end of cycle 2 (each cycle is 21 days)]
The number of participants with relapsed or refractory HCC whose tumors show a response (CR+PR) after 2 cycles of cyclophosphamide, PK-guided sorafenib, bevacizumab and atezolizumab
PK measure of sorafenib
Time frame: At the end of cycle 1 (each cycle is 21 days)]
The number of participants who have a sorafenib systemic exposure between 20 and 55 who experience sorafenib-induced skin toxicity compared to the number of participants who have a systemic sorafenib exposure outside of the 20-55 range who experience sorafenib-induced skin toxicity.
Parts 1 & 2: Intratumoral T-cell infiltration of CD8+C45RO+ cells
Time frame: At the end of cycle 2 (each cycle is 21 days)]
The number of participants whose tumors show an increase in the ratio of CD45RO+/CD3+ T cells of at least 27% OR who show an absolute increase in CD3+ cells from baseline to the end of cycle 2 (approximately 42 days from the start of therapy).

7 secondary outcomes

Part 1:Response rate of relapsed or refractory solid tumors
Time frame: At the end of cycle 2 (each cycle is 21 days)]
Part 2: Response rate of relapsed or refractory fibrolamellar carcinoma, desmoplastic small round cell tumor, malignant rhabdoid tumor
Time frame: At the end of cycle 2 (each cycle is 21 days)]
Resection rate of liver tumors
Time frame: At the end of cycle 1 (each cycle is 21 days)]
Progression Free Survival
Time frame: At the end of cycle 2 (each cycle is 21 days
Event Free Survival
Time frame: At the end of cycle 2 (each cycle is 21 days
Overall Survival
Time frame: At the end of cycle 2 (each cycle is 21 days
Systemic immune activation correlation with tumor response
Time frame: after 2 courses of therapy (each cycle is 21 days

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 19 May 2026.
St. Jude Children's Research HospitalLink provided by the sponsor.
Clinical Trials Open at St. JudeLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

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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.

Jessica Gartrell, MD contact

888-226-4343

referralino@stjude.org

Jessica Gartrell, MD principal investigator

St. Jude Children's Research Hospital

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 31 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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?

Contact Jessica Gartrell, MD (888-226-4343, referralino@stjude.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Recommended phase 2 doses (RP2Ds) (time frame: At the end of cycle 2 (each cycle is 21 days)]). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05468359.

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 19 May 2026.