Atezolizumab and Bevacizumab Before Surgery for the Treatment of Resectable Liver Cancer
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|ClinicalTrials.gov Identifier: NCT04721132|
Recruitment Status : Recruiting
First Posted : January 22, 2021
Last Update Posted : October 13, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Resectable Hepatocellular Carcinoma Stage I Hepatocellular Carcinoma AJCC v8 Stage IA Hepatocellular Carcinoma AJCC v8 Stage IB Hepatocellular Carcinoma AJCC v8 Stage II Hepatocellular Carcinoma AJCC v8||Biological: Atezolizumab Biological: Bevacizumab Procedure: Therapeutic Conventional Surgery||Phase 2|
I. To evaluate safety and tolerability of atezolizumab plus bevacizumab combination therapy in the pre-operative setting.
II. To assess the rate of pathologic complete response.
I. To evaluate the correlation between rate of pathologic complete response, overall response rate at time of surgery (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 and modified RECIST 1.0), duration of response as defined by time to recurrence/recurrence-free survival, in addition to overall survival.
I. To evaluate the predictive value of dynamic changes in fibrosis stage (defined by a minimum 1-point improvement in fibrosis stage 0-4 per magnetic resonance elastography [MRE]) and in IGF-1 blood score.
II. To measure baseline and longitudinal changes of immune infiltration including CD8/regulatory T cell (Treg) ratio and CD68+ density, and fibrosis stage by MRE for up to one year.
Patients receive atezolizumab intravenously (IV) over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery during week 12.
After completion of study treatment, patients are followed up every 3 months for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label, Phase II, Pre-Operative Study of Atezolizumab Plus Bevacizumab for Resectable Hepatocellular Carcinoma|
|Actual Study Start Date :||February 10, 2021|
|Estimated Primary Completion Date :||June 30, 2023|
|Estimated Study Completion Date :||December 31, 2027|
Experimental: Treatment (atezolizumab, bevacizumab)
Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery during week 12.
Procedure: Therapeutic Conventional Surgery
- Pathologic complete response (pCR) rate [ Time Frame: Up to 2 years post-treatment ]Will estimate pCR rate along with the 95% credible interval.
- Incidence of adverse events (AEs) [ Time Frame: Up to 30 days post-treatment ]The AE severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 will be used for assessing AE severity.
- Objective response rate (ORR) [ Time Frame: At the time of surgery ]Objective response is defined as complete response or partial response, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1), modified (m)RECIST1.0. ORR will be summarized along with 95% confidence intervals. Fisher's exact test will be used to correlate pCR and OR.
- Duration of response (DOR) [ Time Frame: From the date of response to the date of recurrence/disease progression, assessed up to 2 years post-treatment ]DOR will be estimated with the Kaplan-Meier methods.
- Recurrence-free survival (RFS) [ Time Frame: From the date of surgery to the date of disease recurrence or death whichever occur first, assessed up to 2 years post-treatment ]RFS will be estimated with the Kaplan-Meier methods. The log-rank test will be used to evaluate the association between pCR and RFS.
- Overall survival (OS) [ Time Frame: From the date of treatment start to the date of death or to the date of last follow-up for patients alive, assessed up to 2 years post-treatment ]OS will be estimated with the Kaplan-Meier methods. The log-rank test will be used to evaluate the association between pCR and OS.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Must provide written informed consent prior to initiating any trial related procedures.
2. Patient must be ≥ 18 years of age 3. Patient has histologically confirmed (if tumor tissue is unavailable, documentation of diagnosis from original biopsy is acceptable) or clinically diagnosed (American Association for the Study of Liver Disease criteria in cirrhotic subjects) hepatocellular carcinoma (HCC).
4. Patient has resectable disease with no evidence of extrahepatic spread The determination of resectability status will ultimately lie in the clinical judgment of the surgical oncologist and medical oncologist involved in the care of the patient.
5. Must have a Child-Turcotte-Pugh score A 6. Must have measurable disease defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and that measures ≥ 10 mm with US, MRI or spiral CT scan 7. Patient has record of treated or absence of esophageal varices by esophagogastroduodenoscopy within 6 months of initiating treatment.
8. Patient must be have a representative tumor specimen or be willing to undergo research biopsy and provide tumor sample for exploratory biomarker research 9. ECOG (Eastern Oncology Cooperative Group) performance status ≥ 1 10. Patient demonstrates adequate organ and marrow function within 14 days of study drug administration:
a. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/μL) b. Lymphocyte count ≥ 0.5 × 109/L (500/μL) c. Platelet count ≥ 100 × 109/L (100,000/μL) without transfusion d. Hemoglobin ≥ 90 g/L (9 g/dL) e. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × upper limit of normal (ULN), with the following exceptions: f. Serum bilirubin ≤ 1.5 × ULN with the following exception: i. Patients with known Gilbert disease: serum bilirubin ≤ 3 × ULN g. Serum creatinine ≤ 1.5 × ULN h. Serum albumin ≥ 25 g/L (2.5 g/dL) i. : international normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN j. Negative human immunodeficiency virus (HIV) test at screening k. UA with protein less than 2+ Patients discovered to have >/= 2 + proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24 hours.
l. m. Documented virology status of hepatitis, as confirmed by screening HBV and HCV tests i. For patients with active HBV: HBV DNA < 500 IU/mL during screening, initiation of anti-HBV treatment at least 14 days prior to randomization and willingness to continue anti-HBV treatment during the study (per local standard of care; e.g., entecavir) 11. Women of childbearing potential (WOCBP) and men with partners of child bearing potential agree to prevent pregnancy using two forms of contraception from the date of Informed Consent through 5 months post last dose of study drug.
12. Women of child bearing potential must have a negative serum pregnancy test result within 14 days of initiating study treatment 13. Women of child bearing potential must not be breastfeeding
- Patient has been treated for this malignancy, has another active malignancy, or has had an active malignancy within the last two years
- Patient has fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Patient has had a bleeding event due to untreated esophageal and/or gastric varices.:
- Patient has history of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abcess within 6 months of initiation of study treatment.
- Patient has history of thrombosis, bleeding diathesis, coagulopathy or significant vascular disease.
Patient has history of hemoptysis within 30 days of initiation of study treatment.7. Patient has serious cardiac disease, including New York Heart association Grade II or greater congestive heart failure, MI, unstable angina, etc.8. Patient has inadequately controlled hypertension (systolic ≥ 150 mmHg and/or diastolic ≥ 100 mmHg)9. Patient has significant pulmonary disease including tuberculosis, pneumonia, pneumonitis, etc.10. Patient requires recurrent drainage procedures including pleural effusion, ascites, etc.11. Patient has had surgical procedure within 6 weeks of initiation of study treatment.12. Patient has history of central nervous system disease.13. Patient has history of severe allergic/anaphylactic reactions to chimeric or humanized antibodies or fusion proteins14. Patient has a known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation15. Patient has known hypersensitivity to bevacizumab16. Patient has had any investigational agents within 28 days prior to initiation of study treatment.17. Patient has history of severe infection within 4 weeks of initiation of treatment18. Patient has history of auto immune disease or auto immune deficiency19. Patient has received stem cell transplantation, liver transplantation, or solid organ transplantation20. Patient has history of other significant comorbidities that would be contraindicated for investigational treatment. 21. Patient has used:
- High dose steroids
- Vaccine of any kind within 4 weeks of initiating study treatment
- Oral or IV antibiotics within 2 weeks of initiating study treatment
- Immunostimulatory agents within 4 weeks of initiating study treatment
- Anticoagulation therapy (aspirin permitted)
- Total parenteral nutrition
22. Patient is pregnant or breastfeeding
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04721132
|Contact: Maen Abdelrahimfirstname.lastname@example.org|
|United States, Texas|
|Houston Methodist Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Maen Abdelrahim 713-441-9948 email@example.com|
|Principal Investigator: Maen Abdelrahim|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Ahmed O. Kaseb 713-792-2828 firstname.lastname@example.org|
|Principal Investigator: Ahmed O. Kaseb|
|Principal Investigator:||Ahmed O Kaseb||M.D. Anderson Cancer Center|
|Responsible Party:||M.D. Anderson Cancer Center|
|Other Study ID Numbers:||
NCI-2020-13744 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2020-0791 ( Other Identifier: M D Anderson Cancer Center )
|First Posted:||January 22, 2021 Key Record Dates|
|Last Update Posted:||October 13, 2022|
|Last Verified:||October 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Antineoplastic Agents, Immunological
Endothelial Growth Factors
Angiogenesis Modulating Agents
Physiological Effects of Drugs