Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Bevacizumab

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Liver Extracts

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Immune Checkpoint Inhibitors

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.

Therapeutic Conventional Surgery

Maen Abdelrahim

Ahmed O. Kaseb

Ahmed O Kaseb

This phase II trial studies the effect of atezolizumab and bevacizumab before surgery in treating patients with liver cancer that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving the combination of atezolizumab and bevacizumab may help to prevent liver cancer from returning after surgery.

PRIMARY OBJECTIVES:

1. To evaluate safety and tolerability of atezolizumab plus bevacizumab combination therapy in the pre-operative setting.
2. To assess the rate of pathologic complete response.

SECONDARY OBJECTIVE:

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.

EXPLORATORY OBJECTIVES:

1. Evaluate the predictive value of dynamic changes in fibrosis stage. Fibrosis stage will be assessed by histology by on serial tissue samples collected at baseline and at time of surgery (at 12 weeks after treatment begins).
2. To measure baseline and longitudinal changes of immune infiltration including CD8/Treg ratio and CD68+ density.
3. To explore the association between PD-L1 (and PD-L2) expression by immunohistochemistry, RNA seq genomic profiling, and antitumor efficacy
4. To evaluate baseline and longitudinal changes of tumor-necrosis factor (TNF)-α, pSTAT3, and c- MET; immune cell density such as frequency of PD-1+4-1BB+ CD8 T cells, pro-inflammatory cytokines, and hepatic fibrosis markers (APRI, FIB-4, hyaluronic acid, FibroTest \[FibroSure\]), non- alcoholic-fatty-liver-disease (NAFLD) fibrosis score (NFS), and enhanced liver fibrosis test (ELF)\] as biomarkers of response to therapy.
5. To assess the impact of therapy on the diversity of the tumor-specific T-cell repertoire
6. To explore the correlation between immunological and molecular changes in tumor tissues and peripheral blood with TTP, time to recurrence, OS, and rate of AEs. In particular, we will evaluate the potential of pre-treatment CD8 T-cell density, PD-L1 expression, and CD68 to CD8 ratio or circulating CD68+DR-/low density to predict responsiveness to checkpoint blockade.

OUTLINE:

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.

Atezolizumab and Bevacizumab Before Surgery for the Treatment of Resectable Liver Cancer

An Open-Label, Phase II, Pre-Operative Study of Atezolizumab Plus Bevacizumab for Resectable Hepatocellular Carcinoma

Will estimate pCR rate along with the 95% credible interval.

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 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.

DOR will be estimated with the Kaplan-Meier methods.

RFS will be estimated with the Kaplan-Meier methods. The log-rank test will be used to evaluate the association between pCR and RFS.

OS will be estimated with the Kaplan-Meier methods. The log-rank test will be used to evaluate the association between pCR and OS.

M.D. Anderson Cancer Center

Patients undergo SBRT every other day for a total of 5 days over 2 weeks.

Patients receive Y-90 radioembolization via injection on day 1.

Quality of Life

Questionnaire Administration

Stereotactic Body Radiation Therapy

Yttrium-90 Microsphere Radioembolization

Nima Nabavizadeh

This phase II trial tests whether Y-90 segmentectomy (internal radiation) versus stereotactic body radiation therapy (external radiation) is more optimal in treating inoperable liver cancer. Y-90 segmentectomy consists into very tiny radioactive glass beads that can be injected into the liver through the blood vessels supplying the liver. Stereotactic body radiation therapy uses special equipment to position a patient and deliver external radiation to tumors with high precision. This study many help doctors determine which treatment, Y-90 segmentectomy or SBRT, works better in treating liver cancer.

PRIMARY OBJECTIVE:

I. Determine feasibility of trial enrollment (enrollment date).

SECONDARY OBJECTIVE:

I. To assess differences in overall survival, local control, time to intrahepatic progression, time to next treatment, rate of liver transplant, toxicity, and patient reported complications and quality of life.

EXPLORATORY OBJECTIVE:

I. Compare cumulative cost of treatment-related medical care at 13 months.

OUTLINE: Patients will be randomized in 1 of 2 arms.

Arm I: Patients undergo SBRT every other day for a total of 5 days over 2 weeks.

Arm II: Patients receive Y-90 radioembolization via injection on day 1.

After completion of study, patients are followed up at 2, 4, and 12 weeks and then every 3 months for 13 months.

Y-90 Versus SBRT for Inoperable HCC

Randomized Prospective Two-Arm Feasibility Trial of Stereotactic Body Radiation Therapy Versus Yttrium-90 Segmentectomy in Inoperable Hepatocellular Carcinoma

Determine feasibility of trial enrollment for two therapeutic groups.

Defined as a Child-Pugh criteria \>= 2 point increase.

Measured by Functional Assessment of Cancer Therapy-Hepatobilliary Cancer compared to baseline.

American Society of Clinical Oncology

Medical Research Foundation, Oregon

Oregon Health and Science University

Radiation Oncology Institute

Radiological Society of North America

OHSU Knight Cancer Institute

Principal Investigator

Durvalumab

Patients receive regorafenib PO QD on days 1-21 and durvalumab IV on day 1. Treatment repeats every 28 days for a maximum of 2 years from registration or until decision to proceed to surgery, disease progression, excessive toxicity, or patient withdrawal.

Regorafenib

Mehmet Akce, MD

Olumide B. Gbolahan

Megan Graham

Aditya Shreenivas

Mehmet Akce

This phase II trial tests whether regorafenib and durvalumab work to shrink tumors in patients with high-risk liver cancer. Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving regorafenib and durvalumab may work better in treating patients with high-risk liver cancer.

PRIMARY OBJECTIVE:

I. To assess the overall response rate (ORR) at 16 weeks post registration.

SECONDARY OBJECTIVES:

I. To assess the rate of patients who undergo surgery during the course of the study.

II. To assess the safety and tolerability of the combination therapy of regorafenib plus durvalumab.

III. To assess the effect of combination therapy on overall survival. IV. To assess the effect of combination therapy on progression-free survival (PFS) in patients that do not undergo resection.

V. To assess the effect of combination therapy on recurrent-free survival (RFS) in patients that have resection.

VI. To assess the rate of pathologic complete response.

CORRELATIVE RESEARCH OBJECTIVE:

I. Analyze the effect of regorafenib and durvalumab on immune biomarkers in the tumor microenvironment and systemic circulation.

OUTLINE:

Patients receive regorafenib orally (PO) once daily (QD) on days 1-21 and durvalumab intravenously (IV) on day 1. Treatment repeats every 28 days for a maximum of 2 years from registration or until decision to proceed to surgery, disease progression, excessive toxicity, or patient withdrawal.

After completion of study treatment, patients are followed every 90 days for 3 years.

Regorafenib and Durvalumab for the Treatment of High-Risk Liver Cancer

Neoadjuvant Regorafenib Plus Durvalumab (MEDI4736) in Patients With High-Risk Hepatocellular Carcinoma

An objective response is defined as a complete response (CR) or partial response (PR). Disease status will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v).1.1 criteria. ORR is defined as the proportion of evaluable patient who experience a CR or PR divided by the total number of evaluable patients. The final ORR point estimate and corresponding 95% confidence interval will be reported.

The proportion of patients who underwent surgery within 4 months of the last treatment dose during the course of the study. The 95% confidence interval calculated by Clopper and Pearson will be reported.

The rate of patients experiencing a grade 3+ adverse event will be reported. Further analyses of adverse event rates will be considered exploratory.

PFS is defined as the time from registration to the first of either disease progression or death from any cause, where disease progression is determined based on RECIST 1.1 criteria. Patients who do not experience disease progression or death while on protocol will be censored at the last disease assessment date. PFS will be estimated using the Kaplan-Meier method. Patients in the primary evaluable population who are not in the resectable evaluable population will be eligible for the analysis of this endpoint. The median PFS and corresponding 95% confidence interval (by Brookmeyer and Crowley) will be reported.

OS is defined as the time from registration to death from any cause. Patients who are alive will be censored at the last follow-up date. OS will be estimated using the Kaplan-Meier method. Patients in the primary evaluable population will be eligible for the analysis of this endpoint.. The median OS and corresponding 95% confidence interval (by Brookmeyer and Crowley) will be reported.

RFS is defined as the time from surgical resection to first of either disease recurrence or death from any cause. Patients who do not experience disease recurrence or death while on protocol will be censored at the last disease assessment date. RFS will be estimated using the Kaplan-Meier method. The resectable evaluable population will be used for the analysis of this endpoint. The median RFS and corresponding 95% confidence interval (by Brookmeyer and Crowley) will be reported.

A pathologic complete response must satisfy all of the following: \*No metastatic disease (i.e. pM0 or pMx, pNo or pNx) \*Zero percent residual tumor cells in the specimen including the presumed prior tumor bed and elsewhere \*Negative resection margin on all margin examined. The proportion of patients experiencing pathologic complete response and corresponding 95% confidence interval will be reported.

National Cancer Institute (NCI)

Academic and Community Cancer Research United

Symptoms and General Pathology

Recurrence

Patients undergo 1 SBPT fraction over 20-30 minutes per day for a total of 5 fractions.

Proton Stereotactic Body Radiation Therapy

Quality-of-Life Assessment

Jonathan B. Ashman, M.D., Ph.D.

This phase II trial studies the effect of stereotactic body proton radiotherapy in treating patients with liver cancer. Proton radiotherapy is a type of treatment that uses high-energy beams to treat tumors.

PRIMARY OBJECTIVE:

I. To determine the 3-month rate of patients experiencing an increase in Child-Pugh (CP) score by 2 or more points of 5-fraction stereotactic body proton radiotherapy (SBPT) in the treatment of hepatocellular carcinoma (HCC).

SECONDARY OBJECTIVES:

I. To determine the 3-month complication rate as defined by grade 3 or higher acute adverse event.

II. To assess late toxicity with 2 year follow-up. III. To estimate the 6-month local control, liver disease control, progression free survival and overall survival.

IV. To determine objective imaging response rates at 6 months by Modified (m) Response Evaluation Criteria in Solid Tumors (RECIST) and RECIST criteria.

V. To determine the value of volumetric imaging analysis compared to mRECIST and RECIST in the setting of HCC treated with stereotactic body radiotherapy (SBRT).

CORRELATIVE AND EXPLORATORY OBJECTIVES:

I. To evaluate patient-reported outcomes. II. To evaluate clinical features, treatment technique, and dose-volume parameters associated with better local control and fewer adverse events.

III. To determine the value of additional imaging analyses and techniques for assessing tumor response after treatment with SBRT IV. To blood bank patient specimens for future analysis.

OUTLINE:

Patients undergo 1 SBPT fraction over 20-30 minutes per day for a total of 5 fractions.

After completion of study treatment, patients are followed up at 2 weeks, 3 , 6, 12 and 24 months, then annually for 3 years.

Stereotactic Body Proton Radiotherapy for the Treatment of Liver Cancer

A Phase II Single Arm Trial of Stereotactic Body Proton Radiotherapy (SBPT) for Hepatocellular Carcinoma

Will be evaluated per the validated measure and presented over time with means and 95% CIs.

Will be associated with better local control and fewer adverse events.

Will be determined assessing tumor response after treatment with SBRT.

The rate will be estimated and a 95% exact binomial confidence interval reported, and then tested utilizing a one-sample test for proportions versus the historical control of 15%.

Defined by grade 3 or higher acute adverse event. Will be calculated and presented with 95% confidence intervals (CI), while continuous outcomes will be presented with mean, median, 95% CI, and interquartile range (IQR).

Defined by grade 3 or higher acute adverse event.

Will be reported via Kaplan-Meier estimates.

Will be determined by Modified (m) Response Evaluation Criteria in Solid Tumors (RECIST) and RECIST criteria. Will be calculated and presented with 95% CI, while continuous outcomes will be presented with mean, median, 95% CI, and IQR.

Will be compared to mRECIST and RECIST in the setting of HCC treated with stereotactic body radiotherapy (SBRT).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Atezolizumab and Bevacizumab Before Surgery for the Treatment of Resectable Liver Cancer	NCT04721132	Resectable Hepa... Stage I Hepatoc... Stage IA Hepato... Stage IB Hepato... Stage II Hepato...	Atezolizumab Bevacizumab Therapeutic Con...	18 Years -	M.D. Anderson Cancer Center
Y-90 Versus SBRT for Inoperable HCC	NCT05157451	Hepatocellular ... Stage I Hepatoc... Stage IA Hepato... Stage IB Hepato... Stage II Hepato... Stage III Hepat... Stage IIIA Hepa... Stage IIIB Hepa... Stage IVA Hepat...	Quality of Life Questionnaire A... Stereotactic Bo... Yttrium-90 Micr...	18 Years -	OHSU Knight Cancer Institute
Regorafenib and Durvalumab for the Treatment of High-Risk Liver Cancer	NCT05194293	Stage IB Hepato... Stage II Hepato... Stage III Hepat... Stage IIIA Hepa...	Durvalumab Regorafenib	18 Years -	Academic and Community Cancer Research United
Stereotactic Body Proton Radiotherapy for the Treatment of Liver Cancer	NCT04805788	Recurrent Hepat... Stage I Hepatoc... Stage II Hepato... Stage III Hepat...	Proton Stereota... Quality-of-Life...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for stage ii hepatocellular carcinoma ajcc v8