Hepatocellular CarcinomaPhase 2NCT04563338
An Exploratory Study of Atezolizumab and Bevacizumab in Hepatocellular Carcinoma and Non-Small Cell Lung Cancer With Liver Metastases (INTEGRATE)
A Phase 2 study testing Atezolizumab and Bevacizumab in people with Hepatocellular Carcinoma and Non-small Cell Lung Cancer Metastatic, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
This study is being done to look at how effective the drug, atezolizumab, with or without the drug bevacizumab, is for people with inoperable liver cancer or non-small lung cancer that has spread to the liver. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Non-small Cell Lung Cancer Metastatic, Liver Metastases
- What is being tested?
- Atezolizumab and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteCanada
- Study dates
- 4 Jun 2021to 31 Aug 2026
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent.
- Be ≥ 18 years of age on day of signing informed consent.
- Have histologically or cytologically confirmed diagnosis of inoperable hepatocellular carcinoma (HCC) or non-squamous non-small cell lung cancer (NSCLC) with liver metastases with at least one measurable lesion.
- NSCLC patients who were previously treated with chemotherapy or treatment naïve patients with a programmed death ligand-1 (PD-L1) tumor proportion score ≥50% or tumor cell score 3/immune cell score 3 are included.
- NSCLC patients must be epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild type.
- HCC patients may be treatment naïve or treated with prior tyrosine kinase inhibitor(s).
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- Have a current liver function meeting Child Pugh Class A (5-6 points) in patients with HCC, with no encephalopathy or ascites.
- Be willing to provide tumor tissue from a core biopsy of a tumor lesion (archival not acceptable). The subject must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy. In addition, the subject must be willing to give blood for correlative studies, and have no contraindications to this.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- Have recovered (to ≤ grade 1) from prior toxicities related to previous treatments at the time of study enrollment, with the exception of alopecia or skin depigmentation.
- Be tested for Hepatitis B-virus surface antigen (HBsAg) status. Patients may be included in the study if they have adequately controlled hepatitis B
- Patients must be tested for hepatitis C virus (HCV) status. Subjects with chronic infection by HCV who are untreated are allowed on study. In addition, subjects with successful HCV treatment are allowed as long as 4 weeks have passed between completion of HCV therapy and start of study treatment.
- Demonstrate adequate organ function.
- Agrees to use use highly effective contraceptive methods, not donate egg or sperm, during study participation, and for at least 6 months after the last dose of study medications.
- Life expectancy expected to be 3 months or greater.
Who cannot join
- Has received stereotactic radiotherapy within 4 weeks of trial commencement. For chemotherapy, tyrosine kinase inhibitors and palliative-dose radiotherapy, a 2 week washout is required.
- Is currently participating and receiving experimental treatment as part of a clinical trial, or has participated in a study of an immune checkpoint inhibitor and received study therapy, or used an investigational device within 4 weeks of the first dose of treatment.
- Inadequately controlled hypertension (defined as systolic blood pressure [BP] > 150 mmHg and/or diastolic blood pressure > 100 mmHg), based on an average of ≥ 3 BP readings on ≥ 2 sessions. Anti-hypertensive therapy to achieve these parameters is allowed.
- History of hypertensive crises or hypertensive encephalopathy
- Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment), unstable arrhythmia, or unstable angina
- Significant vascular disease (eg. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
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- History of Grade ≥ 4 venous thromboembolism.
- History of Grade ≥ 2 hemoptysis (defined as ≥ 2.5 mL of bright red blood per episode) within 1 month prior to screening for HCC and within 3 months for NSCLC.
- History or evidence of bleeding diathesis or significant coagulopathy at risk of bleeding (ie. In the absence of therapeutic anticoagulation)
- Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to initiation of study treatment and wounds are fully healed, or anticipation of need for major surgical procedure during the course of the study.
- Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture.
- Evidence of tumor invading or abutting major blood vessels.
- History of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess, or active GI bleeding within 6 months prior to randomization.
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Current or recent (< 10 days prior to initiation of study treatment) use of aspirin (> 325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel (> 75 mg/day) and cilostazol.
- Current or recent (< 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose
- Has symptomatic, untreated or actively progressing central nervous system (CNS) metastases. Asymptomatic patients treated for CNS metastases may be eligible if they meet required criteria.
- Uncontrolled tumor-related pain
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
- Has had a previous allogeneic stem cell or solid organ transplant, a diagnosis of immunodeficiency, or is receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy (eg. cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF]-α agents) within 7 days prior to the first dose of trial treatment, or anticipation of need for systemic immunosuppressive medication during study treatment.
- Has histological or cytological diagnosis of fibrolamellar HCC, mixed cholangiocarcinoma or sarcomatoid HCC.
- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding
- Has had a prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
- History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to either Atezolizumab or Bevacizumab.
- Has had hepatic encephalopathy in the past 6 months, or has clinically apparent ascites at the time of study enrollment
- History of idiopathic pulmonary fibrosis, organizing pneumonia (eg. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
- Has active Bacillus Tuberculosis (TB)
- Has had prior treatment-related toxicity and not recovered (i.e. ≤ Grade 1 or at baseline)
- Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
- Has a known history of prior clinically relevant invasive malignancy except if the subject has undergone curative-intent therapy with no evidence of disease recurrence for 2 years prior to study entry. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, low-risk prostate cancer or in-situ cervical cancer.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy at a dose of ≤ 10 mg/day of prednisolone or equivalent) is not considered a form of systemic therapy.
- Has a known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic oral or intravenous (IV) antibiotic therapy within 2 weeks prior to initiation of treatment.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subjects participation for the full duration of the trial, or is not in the best interest of the subject to participate in the opinion of the treating investigator.
- Has known psychiatric, substance abuse disorder, or any other condition that, in the opinion of the investigator, would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through at least 6 months after the last dose of study drugs
- Has received prior therapy with CD137 agonists or immune checkpoint blockade therapies including anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4), anti-programmed death-1 (PD-1), anti-PD-L1, anti-programmed death ligand-2 (PD-L2) agent, or bevacizumab.
- Has a known history of Human Immunodeficiency Virus (HIV)
- Has received a live vaccine within 30 days of planned start of study therapy or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Exploratory Evaluation of the Evolution of the Tumor Immune Microenvironment in Hepatocellular Carcinoma and Non-Small Cell Lung Cancer With Liver Metastases Treated With Atezolizumab and Bevacizumab (INTEGRATE)
This study is being done to look at how effective the drug, atezolizumab, with or without the drug bevacizumab, is for people with inoperable liver cancer or non-small lung cancer that has spread to the liver. This will be done by looking at the duration of time from starting the study drug(s) until the cancer worsens in study participants.
This study will collect blood and tumor tissue samples from participants to look at changes to their tumor(s) before and after receiving atezolizumab and/or bevacizumab.
Read the detailed description
Participants with liver cancer will be assigned to Arm A and receive atezolizumab and bevacizumab.
Participants with non-small cell lung cancer will be randomized into one of the following arms:
- Arm B: Atezolizumab and bevacizumab
- Arm C: Atezolizumab alone
Participants randomized to Arm C whose disease worsens may be able to cross over to Arm B and receive atezolizumab and bevacizumab together.
- Being tested
- Atezolizumab, Bevacizumab
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Also called TECENTRIQ
Atezolizumab is a type of drug called a monoclonal antibody. Antibodies are proteins that are naturally found in the blood stream that fight infections. Monoclonal antibodies are a special kind of antibody that is created in a laboratory. These drugs bind (attaches) to specific proteins in the body that may be involved in cancers. Atezolizumab binds to PD-L1 which is a protein involved preventing the body's immune system (defense system against infection and disease) from fighting cancer cells. Blocking PD-L1 is expected to help the immune cells to destroy the cancer cells.
BevacizumabDrug
Also called AVASTIN
Bevacizumab is a type of drug called a monoclonal antibody. Antibodies are proteins that are naturally found in the blood stream that fight infections. Monoclonal antibodies are a special kind of antibody that is created in a laboratory. These drugs bind (attaches) to specific proteins in the body that may be involved in cancers. Bevacizumab binds to vascular endothelial growth factor (VEGF) which is a protein involved with the growth of new blood vessels. Blocking VEGF will prevent blood vessels from forming and therefore stopping oxygen and nutrients to be supplied to cancer cells. Without oxygen and nutrients, the cancer cells will die.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (Liver Cancer) | Experimental | Atezolizumab: 1200 mg, intravenously (IV), every 3 weeks
Bevacizumab: 15 mg/kg, intravenously (IV), every 3 weeks Receives: Drug: Atezolizumab; Drug: Bevacizumab |
| Arm B (Lung Cancer) | Experimental | Atezolizumab: 1200 mg, intravenously (IV), every 3 weeks
Bevacizumab: 15 mg/kg, intravenously (IV), every 3 weeks Receives: Drug: Atezolizumab; Drug: Bevacizumab |
| Arm C (Lung Cancer) | Experimental | Atezolizumab: 1200 mg, intravenously (IV), every 3 weeks Receives: Drug: Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Time from enrollment until the date of objective disease progression
Measured: 4 years
Secondary outcomes (4)
Overall response rate
Measured: 4 years
Average duration of response
Measured: 4 years
Overall survival rate
Measured: 2 years
Progression-free survival rate
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2020
- Study start4 Jun 2021
- Primary completion25 Jun 2024
- Study completion31 Aug 2026 (estimated)
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 Health Network, TorontoThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel with potential crossover from Arm C to Arm B.
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Adrian Sacher, MD, Principal investigator, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04563338
- Sponsor's protocol ID
- INTEGRATE
- Other IDs
- CAPCR 20-5808
- Status last verified
- Mar 2026
- First submitted
- 21 Sep 2020
- Last updated
- 5 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Evaluation of the Evolution of the Tumor Immune Microenvironment in Hepatocellular Carcinoma and Non-Small Cell Lung Cancer With Liver Metastases Treated With Atezolizumab and Bevacizumab (INTEGRATE)
- ClinicalTrials.gov ID
- NCT04563338
- Acronym / sponsor ID
- INTEGRATE
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- 4 Jun 2021 (actual)
- Primary completion
- 25 Jun 2024 (actual)
- Study completion
- 31 Aug 2026 (estimated)
- First posted
- 24 Sep 2020 (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 study is being done to look at how effective the drug, atezolizumab, with or without the drug bevacizumab, is for people with inoperable liver cancer or non-small lung cancer that has spread to the liver. This will be done by looking at the duration of time from starting the study drug(s) until the cancer worsens in study participants.
This study will collect blood and tumor tissue samples from participants to look at changes to their tumor(s) before and after receiving atezolizumab and/or bevacizumab.
Detailed description
Participants with liver cancer will be assigned to Arm A and receive atezolizumab and bevacizumab.
Participants with non-small cell lung cancer will be randomized into one of the following arms:
- Arm B: Atezolizumab and bevacizumab
- Arm C: Atezolizumab alone
Participants randomized to Arm C whose disease worsens may be able to cross over to Arm B and receive atezolizumab and bevacizumab together.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Parallel with potential crossover from Arm C to Arm B.
| Arm | Type | Receives |
|---|---|---|
| Arm A (Liver Cancer) | Experimental | Drug: Atezolizumab, Drug: BevacizumabAtezolizumab: 1200 mg, intravenously (IV), every 3 weeks Bevacizumab: 15 mg/kg, intravenously (IV), every 3 weeks |
| Arm B (Lung Cancer) | Experimental | Drug: Atezolizumab, Drug: BevacizumabAtezolizumab: 1200 mg, intravenously (IV), every 3 weeks Bevacizumab: 15 mg/kg, intravenously (IV), every 3 weeks |
| Arm C (Lung Cancer) | Experimental | Drug: AtezolizumabAtezolizumab: 1200 mg, intravenously (IV), 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 (15 listed)
- Be willing and able to provide written informed consent.
- Be ≥ 18 years of age on day of signing informed consent.
- Have histologically or cytologically confirmed diagnosis of inoperable hepatocellular carcinoma (HCC) or non-squamous non-small cell lung cancer (NSCLC) with liver metastases with at least one measurable lesion.
- NSCLC patients who were previously treated with chemotherapy or treatment naïve patients with a programmed death ligand-1 (PD-L1) tumor proportion score ≥50% or tumor cell score 3/immune cell score 3 are included.
- NSCLC patients must be epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild type.
Key exclusion criteria (39 listed)
- Has received stereotactic radiotherapy within 4 weeks of trial commencement. For chemotherapy, tyrosine kinase inhibitors and palliative-dose radiotherapy, a 2 week washout is required.
- Is currently participating and receiving experimental treatment as part of a clinical trial, or has participated in a study of an immune checkpoint inhibitor and received study therapy, or used an investigational device within 4 weeks of the first dose of treatment.
- Inadequately controlled hypertension (defined as systolic blood pressure [BP] > 150 mmHg and/or diastolic blood pressure > 100 mmHg), based on an average of ≥ 3 BP readings on ≥ 2 sessions. Anti-hypertensive therapy to achieve these parameters is allowed.
- History of hypertensive crises or hypertensive encephalopathy
- Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment), unstable arrhythmia, or unstable angina
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: TECENTRIQAtezolizumab is a type of drug called a monoclonal antibody. Antibodies are proteins that are naturally found in the blood stream that fight infections. Monoclonal antibodies are a special kind of antibody that is created in a laboratory. These drugs bind (attaches) to specific proteins in the body that may be involved in cancers. Atezolizumab binds to PD-L1 which is a protein involved preventing the body's immune system (defense system against infection and disease) from fighting cancer cells. Blocking PD-L1 is expected to help the immune cells to destroy the cancer cells. | Drug | Arm A (Liver Cancer), Arm B (Lung Cancer), Arm C (Lung Cancer) |
| BevacizumabAlso: AVASTINBevacizumab is a type of drug called a monoclonal antibody. Antibodies are proteins that are naturally found in the blood stream that fight infections. Monoclonal antibodies are a special kind of antibody that is created in a laboratory. These drugs bind (attaches) to specific proteins in the body that may be involved in cancers. Bevacizumab binds to vascular endothelial growth factor (VEGF) which is a protein involved with the growth of new blood vessels. Blocking VEGF will prevent blood vessels from forming and therefore stopping oxygen and nutrients to be supplied to cancer cells. Without oxygen and nutrients, the cancer cells will die. | Drug | Arm A (Liver Cancer), Arm B (Lung Cancer) |
Primary outcome
Progression-free survival
Time frame: 4 years
Time from enrollment until the date of objective disease progression
4 secondary outcomes
Overall response rate
Time frame: 4 years
Average duration of response
Time frame: 4 years
Overall survival rate
Time frame: 2 years
Progression-free survival rate
Time frame: 1 year
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 5 Mar 2026.
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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.
Adrian Sacher, MD principal investigator
Princess Margaret Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atezolizumab and Bevacizumab in people with Hepatocellular Carcinoma and Non-small Cell Lung Cancer Metastatic, run by University Health Network, Toronto at 1 site in Canada.
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 15 inclusion and 39 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: under way, not looking for participants, as of the sponsor's last update on 5 Mar 2026. 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 Canada. 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 phase mean?
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?
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?
Progression-free survival (time frame: 4 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 5 Mar 2026.