Hepatocellular CarcinomaPhase 1/2NCT05109052
Trial of PXS-5505 Combined With First Line Atezolizumab Plus Bevacizumab For Treating Patients With Unresectable Hepatocellular Carcinoma
A Phase 1/2 study testing PXS-5505 and Atezolizumab and Bevacizumab in people with Hepatocellular Carcinoma and Cancer of Liver, run by University of Rochester at 1 site in United States.
Trial summary
This trial will assess the safety and tolerability of PXS-5505 incorporating first-line combination therapy Atezolizumab and Bevacizumab in unresectable or metastatic hepatocellular carcinoma. Phase 2 will assess the efficacy of this combination therapy in unresectable or metastatic hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Cancer of Liver
- What is being tested?
- PXS-5505 and Atezolizumab and Bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Sep 2022to 31 Dec 2028
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient or legally authorized representative must be able to understand and willing to sign an IRB approved written informed consent document.
- Patients must be 18 years or older
- Patient must have histological or radiographically confirmed unresectable or metastatic hepatocellular carcinoma.
- Patients must have no concomitant active oncologic diagnosis
- Patient must have at least one radiographically measurable lesion defined as non-radiated lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 10mm with calipers by radiographic exam. Further details listed in section 5.5.
- Patient must have received no previous systemic or investigational therapy for the treatment of HCC. Patients who previously received locoregional therapies remain eligible for this study.
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- Patient must have a life expectancy of minimum 3 months.
- Patient must have normal bone marrow and organ function as defined below.
- Absolute neutrophil count >1,500/mcl
- Platelets >75,000/ul without transfusion
- Hemoglobin >9.0 g/dL
- Creatinine should be below the upper limit of normal OR
- Creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Aspartate aminotransferase (AST), Alanine transaminase (ALT), and alkaline phosphatase (ALP) <5 times the upper limit of normal
- Serum bilirubin no greater than 1.5-2x the upper limit of normal
- Patient not on anticoagulation must have international Normalized Ratio (INR) and activated partial thromboplastin time (PTT) <1.7 upper limit of normal. Patients on anticoagulation may be included, provided they can be off anticoagulation as indicated for paired biopsy collection.
- Patient will have an ECOG performance status of 0 or 1
- Patient must consent for baseline and on treatment biopsies, if prior baseline biopsies have been performed, and stored within the University of Rochester Cancer Library, then baseline biopsies are not necessary.
- Patients must be Child-Pugh class A or less
- Female subjects of childbearing potential must demonstrate a negative urine or serum pregnancy test.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) for a duration consistent with that described in the Bevacizumab and Atezolizumab labels (i.e. 6 months). Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Male subjects with a female partner of child-bearing potential must agree to use 2 adequate methods of contraception (barrier + hormonal for example).
Who cannot join
- Patient with any histologic variant of HCC such as fibrolamellar, sarcomatous, or mixed cholangiocarcinoma and HCC.
- Patient has a history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only, carcinoma in situ of the cervix, or prostate cancer that does not require treatment.
- Patient who received a previous systemic therapy for hepatocellular carcinoma or has tumor recurrence sooner than 6 months after completion of the last dose of therapy.
- Patient who is receiving any other investigational agent
- Patient has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXS-5505, Atezolizumab, or Bevacizumab
- Patient with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, any clinically active malabsorption syndrome, inflammatory bowel disease, any condition that increases the risk of severe gastrointestinal toxicity, or psychiatric illness/social situations that would limit compliance with study requirements
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- Has current active autoimmune disease, or a documented history of autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, resolved childhood asthma/atopy, hypothyroidism on thyroid supplementation, and type 1 diabetics would be exception to this rule.
- Patients who are eligible for liver transplantation
- Has had an allogenic tissue/solid organ transplant.
- Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
- Has received or plans to receive a live vaccine within 30 days prior to the first administration of study medication. Flu vaccines that do not contain live virus are permitted.
- Has known active Hepatitis B or C.
- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding
- A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Inadequately controlled arterial hypertension
- Prior history of hypertensive crisis or hypertensive encephalopathy
- Evidence of bleeding diathesis or significant coagulopathy
- Inability to tolerate oral medications
- Child Pugh B or C cirrhosis
- Known connective tissue disorder
- Evidence of vascular aneurysmal disease
- History of myeloproliferative, myelodysplastic disorders, or monoclonal gammopathy of undetermined significance
- Major surgery within 4 weeks of enrollment
- Patient who is pregnant and/or breastfeeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1b/2 Trial of PXS-5505 Combined With First Line Atezolizumab Plus Bevacizumab For Treating Patients With Unresectable Hepatocellular Carcinoma
This trial will assess the safety and tolerability of PXS-5505 incorporating first-line combination therapy Atezolizumab and Bevacizumab in unresectable or metastatic hepatocellular carcinoma. Phase 2 will assess the efficacy of this combination therapy in unresectable or metastatic hepatocellular carcinoma.
Read the detailed description
Primary liver malignancies have doubled in incidence over the last two decades. These malignancies are now the 4th leading cause of cancer-related mortality worldwide with a 19.6% 5-year relative survival. Hepatocellular carcinoma (HCC) accounts for 90% with cholangiocarcinoma (CCA) accounting for the remainder. Currently, just 20-30% are resectable at presentation with many patients relying on systemic therapy. Beyond resection, effective systemic therapies are lacking, thus new treatment regimens are of significant clinical need. Recent phase III data with combination of Atezolizumab (anti-PD-L1) and Bevacizumab (anti-VEGF) as first-line therapy in unresectable HCC demonstrated improved progression-free and overall survival compared to Sorafenib, thus bringing immunotherapy to the forefront of combating this disease. Despite this improvement, patients experience significantly more adverse events with the addition of anti-VEGF therapy. This combination of Atezolizumab and Bevacizumab is an attractive immunotherapeutic backbone for pairing HCC therapy with means to improve drug delivery and boost response in order to decrease anti-VEGF dosing.
HCC most often develops in the background of chronic inflammation from sustained liver damage, hepatocyte cell death, and compensatory proliferation. During liver injury, hepatic stellate cells (HSCs) transform from quiescent to activated cells, characterized by altered matrix protease activity and deposition of extracellular matrix (ECM) proteins. ECM deposition increases liver stiffness that leads to vascular resistance and hypoxia, stimulating pro-angiogenic factors and subsequent angiogenesis. Secretion of growth factors (TGF-β, PDGF, and FGF-2) by the ECM and tumor cells, attracts fibroblasts from neighboring tissues and aids in transformation to cancer-associated fibroblasts (CAFs).[23] CAFs interplay with the ECM, contributing to further desmoplasia and remodeling through secretion of lysyl oxidases that catalyze collagen cross-linking. The accumulation of collagen cross-links results in marked increase in stromal stiffening and interstitial fluid pressure (IFP) reducing delivery of chemotherapy and immunotherapy Lysyl oxidases (LOX) are a family of 5 secreted copper-dependent amine oxidases (LOX, LOXL1-4) that catalyze the cross-linking of collagen and elastin in the extracellular matrix. High LOX expression has been show to correlate with poor prognosis across a variety of solid malignancies, including hepatocellular carcinoma. This trial pairs PXS-5505 (pan-lysyl oxidase inhibitor) with Atezolizumab and Bevacizumab in patients with unresectable or metastatic HCC. Phase 1b of this study will be an open label safety and tolerability assessment of PXS-5505 (pan-lysyl oxidase inhibitor) with a dose escalation design. The Phase 2 portion of the study will assess the efficacy of combination PXS-5505 with Atezolizumab and Bevacizumab compared to historical standard of care Atezolizumab and Bevacizumab.
- Conditions
- Hepatocellular Carcinoma, Cancer of Liver
- Being tested
- PXS-5505 and Atezolizumab and Bevacizumab
- Keywords
- Hepatocellular Carcinoma, Cancer of Liver, PXS-5505
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PXS-5505 and Atezolizumab and BevacizumabDrug
Open label safety and tolerability assessment of PXS-5505 incorporating first-line combination therapy Atezolizumab and Bevacizumab
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Open label safety and tolerability assessment of PXS-5505:
(PXS-5505) 100-200mg BID (Atezolizumab) 1200mg every 3 weeks (Bevacizumab) 15mg/kg every 3 weeks Receives: Drug: PXS-5505 and Atezolizumab and Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
measured by adverse event severity and quantity
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2021
- Study start20 Sep 2022
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Why it stopped: no accrual of eligible participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by University of RochesterThe 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nabeel Badri, University of Rochester
- Investigators
- Nabeel Badri, Principal investigator, Univ. of Rochester Wilmot Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05109052
- Sponsor's protocol ID
- SGIH21023
- Status last verified
- Jul 2023
- First submitted
- 15 Sep 2021
- Last updated
- 13 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Trial of PXS-5505 Combined With First Line Atezolizumab Plus Bevacizumab For Treating Patients With Unresectable Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05109052
- Acronym / sponsor ID
- SGIH21023
- Conditions
- Hepatocellular Carcinoma, Cancer of Liver
- Keywords
- Hepatocellular Carcinoma, Cancer of Liver, PXS-5505
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: no accrual of eligible participants
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- 20 Sep 2022 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 5 Nov 2021 (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.
This trial will assess the safety and tolerability of PXS-5505 incorporating first-line combination therapy Atezolizumab and Bevacizumab in unresectable or metastatic hepatocellular carcinoma. Phase 2 will assess the efficacy of this combination therapy in unresectable or metastatic hepatocellular carcinoma.
Detailed description
Primary liver malignancies have doubled in incidence over the last two decades. These malignancies are now the 4th leading cause of cancer-related mortality worldwide with a 19.6% 5-year relative survival. Hepatocellular carcinoma (HCC) accounts for 90% with cholangiocarcinoma (CCA) accounting for the remainder. Currently, just 20-30% are resectable at presentation with many patients relying on systemic therapy. Beyond resection, effective systemic therapies are lacking, thus new treatment regimens are of significant clinical need. Recent phase III data with combination of Atezolizumab (anti-PD-L1) and Bevacizumab (anti-VEGF) as first-line therapy in unresectable HCC demonstrated improved progression-free and overall survival compared to Sorafenib, thus bringing immunotherapy to the forefront of combating this disease. Despite this improvement, patients experience significantly more adverse events with the addition of anti-VEGF therapy. This combination of Atezolizumab and Bevacizumab is an attractive immunotherapeutic backbone for pairing HCC therapy with means to improve drug delivery and boost response in order to decrease anti-VEGF dosing.
HCC most often develops in the background of chronic inflammation from sustained liver damage, hepatocyte cell death, and compensatory proliferation. During liver injury, hepatic stellate cells (HSCs) transform from quiescent to activated cells, characterized by altered matrix protease activity and deposition of extracellular matrix (ECM) proteins. ECM deposition increases liver stiffness that leads to vascular resistance and hypoxia, stimulating pro-angiogenic factors and subsequent angiogenesis. Secretion of growth factors (TGF-β, PDGF, and FGF-2) by the ECM and tumor cells, attracts fibroblasts from neighboring tissues and aids in transformation to cancer-associated fibroblasts (CAFs).[23] CAFs interplay with the ECM, contributing to further desmoplasia and remodeling through secretion of lysyl oxidases that catalyze collagen cross-linking. The accumulation of collagen cross-links results in marked increase in stromal stiffening and interstitial fluid pressure (IFP) reducing delivery of chemotherapy and immunotherapy Lysyl oxidases (LOX) are a family of 5 secreted copper-dependent amine oxidases (LOX, LOXL1-4) that catalyze the cross-linking of collagen and elastin in the extracellular matrix. High LOX expression has been show to correlate with poor prognosis across a variety of solid malignancies, including hepatocellular carcinoma. This trial pairs PXS-5505 (pan-lysyl oxidase inhibitor) with Atezolizumab and Bevacizumab in patients with unresectable or metastatic HCC. Phase 1b of this study will be an open label safety and tolerability assessment of PXS-5505 (pan-lysyl oxidase inhibitor) with a dose escalation design. The Phase 2 portion of the study will assess the efficacy of combination PXS-5505 with Atezolizumab and Bevacizumab compared to historical standard of care Atezolizumab and Bevacizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: PXS-5505 and Atezolizumab and BevacizumabOpen label safety and tolerability assessment of PXS-5505: (PXS-5505) 100-200mg BID (Atezolizumab) 1200mg every 3 weeks (Bevacizumab) 15mg/kg every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patient or legally authorized representative must be able to understand and willing to sign an IRB approved written informed consent document.
- Patients must be 18 years or older
- Patient must have histological or radiographically confirmed unresectable or metastatic hepatocellular carcinoma.
- Patients must have no concomitant active oncologic diagnosis
- Patient must have at least one radiographically measurable lesion defined as non-radiated lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 10mm with calipers by radiographic exam. Further details listed in section 5.5.
Key exclusion criteria (25 listed)
- Patient with any histologic variant of HCC such as fibrolamellar, sarcomatous, or mixed cholangiocarcinoma and HCC.
- Patient has a history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only, carcinoma in situ of the cervix, or prostate cancer that does not require treatment.
- Patient who received a previous systemic therapy for hepatocellular carcinoma or has tumor recurrence sooner than 6 months after completion of the last dose of therapy.
- Patient who is receiving any other investigational agent
- Patient has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXS-5505, Atezolizumab, or Bevacizumab
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 |
|---|---|---|
| PXS-5505 and Atezolizumab and BevacizumabOpen label safety and tolerability assessment of PXS-5505 incorporating first-line combination therapy Atezolizumab and Bevacizumab | Drug | Experimental |
Primary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 10 years
measured by adverse event severity and quantity
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2023.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Nabeel Badri principal investigator
Univ. of Rochester Wilmot Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PXS-5505 and Atezolizumab and Bevacizumab in people with Hepatocellular Carcinoma and Cancer of Liver, run by University of Rochester at 1 site in United States.
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 22 inclusion and 25 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: withdrawn, as of the sponsor's last update on 13 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jul 2023.