Erlotinib Plus Bevacizumab in Hepatocellular Carcinoma (HCC) as Second-line Therapy

NCT01180959 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2009-0260NCI-2011-00723
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if the combination of AvastinTM (bevacizumab) and Tarceva (erlotinib hydrochloride) can help to control advanced liver cancer. The safety of this drug combination will also be studied.

Conditions

Liver Cancer

Keywords

Advanced Liver Cancer; primary neoplasm of the liver; Erlotinib; Bevacizumab; Hepatocellular Carcinoma; HCC; Avastin; Anti-VEGF monoclonal antibody; rhuMAb-VEGF; OSI-774; Tarceva

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Progression-free survival is defined as time from initiation of therapy until documented disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  59 months

Secondary Outcomes (2)

• Time to Progression (TTP)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 16 weeks

• Overall Survival (OS)

  24 months

Study Arms (1)

Erlotinib + Bevacizumab

EXPERIMENTAL

Erlotinib 150 mg by mouth once a day. Bevacizumab 10 mg/kg by vein once every 2 weeks on days 1 and 15 of each cycle. The first dose of bevacizumab will be given over about 90 minutes.

Drug: Bevacizumab; Drug: Erlotinib

Interventions

Bevacizumab DRUG

10 mg/kg by vein once every 2 weeks on days 1 and 15 of each cycle. The first dose of bevacizumab will be given over about 90 minutes

Also known as: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Erlotinib + Bevacizumab

Erlotinib DRUG

150 mg by mouth once a day.

Also known as: OSI-774, Tarceva

Erlotinib + Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Patients with histological or cytologically documented HCC not amenable to curative resection (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects is required. For subjects without cirrhosis, histological or cytological confirmation is mandatory.
• Patients must have measurable disease as per the modified RECIST criteria. Measurable target lesions are defined at baseline as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) \>/= 20 mm using conventional techniques (CT or MRI) or \>/= 10 mm using spiral CT scan. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation.
• Patients who have progressed on, or were intolerant to, one prior systemic therapy with sorafenib, completed ≥ 14 days prior to treatment day 1. Previous treatments also allowed that do not count as systemic therapy include: surgical resection, transarterial embolization/chemoembolization (TAE/TACE), radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), provided that the lesion(s) to be evaluated in this study are separate from the previously treated lesions(s).
• Eastern Cooperative Oncology Group (ECOG) performance status of \</= 2.
• Childs-Pugh liver function status of A or B (only 7 points allowed).
• Organ function: Absolute peripheral granulocyte count of \>/= 1500 mm\^3, platelet count of \>/= 40,000 mm\^3, hemoglobin \>/= 10 gm/dL. Total bilirubin \</= 2.0 gm/dL; serum albumin \>/= 2.5 gm/dL; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) up to 5 X the upper limit of institutional normal (AST - 46 and ALT - 56); and prothrombin time prolonged not more than 3 seconds greater than institutional normal, once attempts to correct a prolonged PT have been made.
• (Continuation of # 6) Patients who require full dose anticoagulation, who are otherwise eligible for this trial, are allowed to have an appropriately prolonged International Normalized Ratio (INR).
• Negative serum pregnancy test in women with childbearing potential (those who are not surgically sterilized or who are not amenorrheic for \>/= 12 months), within one week prior to initiation of treatment.
• Men and women of childbearing potential must agree to use effective means of contraception prior to study entry and for at least 180 days after the last dose of study treatment. They must agree to use two forms of birth control, for example, barrier methods (such as a diaphragm, cervical cap, contraceptive sponge, female condom, or male condom), and an intrauterine device (IUD).
• Age \>/= 18 years. The agents bevacizumab and erlotinib have not been studied in pediatric patients, thus the doses to be used in this study cannot be assumed to be safe in children.
• Radiographic evidence of disease progression during or following prior treatment with sorafenib.
• Patients must have proteinuria \< 2+ or a urine protein:creatinine (UPC) ratio \< 1.0. Patients who have proteinuria \>/= 2+ and UPC ratio \>/= 1.0 must undergo a 24 hour urine collection and must demonstrate \</= 1g of protein in 24 hours to be eligible.

You may not qualify if:

• Patients who have had prior systemic therapy other than sorafenib. Patients may not have received any systemic chemotherapy \</=14 days of Treatment Day 1.
• Active malignancy other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years.
• Current, recent (within 4 weeks of Treatment Day 1) or planned participation in an experimental drug study, other than this study.
• Gastrointestinal disease resulting in an inability to take oral medication or a requirement for intravenous hyperalimentation.
• History of rupture of existing HCC lesion, or HCC lesion with large necrotic areas seen on conventional imaging studies, as determined by the Principal Investigator, if there is no measurable solid tumor area \> 1.5 cm.
• Inadequately controlled hypertension (defined as systolic blood pressure \>140 and/or diastolic blood pressure \> 90).
• Prior history of hypertensive crisis or hypertensive encephalopathy.
• New York Heart Association Class II or greater congestive heart failure.
• Cardiac arrhythmia not controlled by medication.
• History of myocardial infarction or unstable angina within 6 months of Treatment Day 1.
• History of stroke or transient ischemic attack within 6 months prior to Day 1 of treatment.
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1.
• Evidence of clinically significant \[Common Terminology Criteria (CTC) Grade 3 or 4\] venous or arterial thrombotic disease within previous 6 months.
• Radiographic evidence of major tumor thrombus in the vena cava.
• History of hemoptysis (\>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator
• OSI Pharmaceuticals: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Kaseb AO, Morris JS, Iwasaki M, Al-Shamsi HO, Raghav KP, Girard L, Cheung S, Nguyen V, Elsayes KM, Xiao L, Abdel-Wahab R, Shalaby AS, Hassan M, Hassabo HM, Wolff RA, Yao JC. Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma. Onco Targets Ther. 2016 Feb 15;9:773-80. doi: 10.2147/OTT.S91977. eCollection 2016.

  PMID: 26929648 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Bevacizumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Ahmed Kaseb, MD- Professor, GI Medical Oncology
• Organization: UT MD Anderson Cancer Center

akaseb@mdanderson.org

(713) 792-2828

Study Officials

• Ahmed Kaseb, MBBS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: August 11, 2010
• First Posted: August 12, 2010
• Study Start: April 14, 2011
• Primary Completion: May 19, 2021
• Study Completion: May 19, 2021
• Last Updated: November 7, 2022
• Results First Posted: November 7, 2022

Record last verified: 2022-11

Locations

US (1)