An Exploratory Study of Atezolizumab and Bevacizumab in Hepatocellular Carcinoma and Non-Small Cell Lung Cancer With Liver Metastases (INTEGRATE)

NCT04563338 | Active Not Recruiting Phase 2

• 2 other identifiers: INTEGRATECAPCR 20-5808
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Hepatocellular Carcinoma; Liver Metastases; Non-small Cell Lung Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Time from enrollment until the date of objective disease progression

  4 years

Secondary Outcomes (4)

• Overall response rate

  4 years

• Average duration of response

  4 years

• Overall survival rate

  2 years

• Progression-free survival rate

  1 year

Study Arms (3)

Arm A (Liver Cancer)

EXPERIMENTAL

Atezolizumab: 1200 mg, intravenously (IV), every 3 weeks Bevacizumab: 15 mg/kg, intravenously (IV), every 3 weeks

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

Drug: Atezolizumab; Drug: Bevacizumab

Arm C (Lung Cancer)

EXPERIMENTAL

Atezolizumab: 1200 mg, intravenously (IV), every 3 weeks

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

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.

Also known as: TECENTRIQ

Arm A (Liver Cancer); Arm B (Lung Cancer); Arm C (Lung Cancer)

Bevacizumab DRUG

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.

Also known as: AVASTIN

Arm A (Liver Cancer); Arm B (Lung Cancer)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Adrian Sacher, MD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel with potential crossover from Arm C to Arm B.

Study Record Dates

• First Submitted: September 21, 2020
• First Posted: September 24, 2020
• Study Start: June 4, 2021
• Primary Completion: June 25, 2024
• Study Completion (Estimated): August 31, 2026
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

CA (1)