Bevacizumab and Erlotinib or Sorafenib as First-Line Therapy in Treating Patients With Advanced Liver Cancer

NCT00881751 | Completed Phase 2 Results DMC

• 3 other identifiers: 101282MUSC-101282GENENTECH-AVF4481s
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 6

Brief Summary

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab, erlotinib, and sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving bevacizumab together with erlotinib is more effective than giving sorafenib in treating patients with liver cancer. PURPOSE: This randomized phase II trial is studying how well giving bevacizumab together with erlotinib works compared with sorafenib as first-line therapy in treating patients with advanced liver cancer.

Conditions

Liver Cancer

Keywords

adult primary hepatocellular carcinoma; advanced adult primary liver cancer; recurrent adult primary liver cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival is defined as the time from treatment day 1 until death from any cause. Patients still alive at the end of follow up,patients who withdrew consent from the trial and patients who were lost to follow up will have their survival time censored at the last date of contact.

  from date of day 1 until the date of death

Secondary Outcomes (3)

• Event-free Survival

  From the time of randomization until progression, withdrawal due to toxicity or any other clinical event requiring withdrawal from the study.

• Number of SAEs Experienced

  From day 1 of drug administration until 30 days after the last dose of study drug.

• Response Rate

  From day 1 drug administration until 30 days after the last dose of study drug.

Study Arms (2)

Arm 1: bevacizumab and erlotinib

EXPERIMENTAL

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28.

Biological: bevacizumab; Drug: erlotinib hydrochloride

Arm 2: sorafenib tosylate

ACTIVE COMPARATOR

Patients receive oral sorafenib tosylate twice daily on days 1-28.

Drug: sorafenib tosylate

Interventions

bevacizumab BIOLOGICAL

Given IV

Arm 1: bevacizumab and erlotinib

erlotinib hydrochloride DRUG

Given orally

Arm 1: bevacizumab and erlotinib

sorafenib tosylate DRUG

Given orally

Arm 2: sorafenib tosylate

Eligibility Criteria

• Age: 18 Years - 116 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Pathologically confirmed advanced hepatocellular carcinoma (HCC) * Childs-Pugh class A * CLIP score ≤ 5 * Not a candidate for curative surgical resection or loco-regional therapy * Measurable disease as per RECIST 1.1 criteria, defined as ≥ 1 previously unirradiated, bidimensionally measurable lesion ≥ 20 mm by CT scan or MRI (triphasic spiral CT scan or MRI employing a "liver protocol" image capture technique required) * Bone lesions, ascites, and pleural effusions are not considered measurable lesions * No fibrolamellar HCC * No known brain metastases * No prior organ transplantation PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 75,000/mm³ * Hemoglobin ≥ 9 g/dL * Transaminases ≤ 5 times upper limit of normal (ULN) * Total bilirubin ≤ 2.0 times ULN * PT ≤ 1.8 times ULN * Prolonged INR allowed for patients who require full dose anticoagulation * Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 45 mL/min * Urine protein \< 2+ by urine dipstick OR urine protein ≤ 1 g by 24-hour urine collection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 12 weeks after completion of study treatment * Able to take and absorb oral medication * No active infection requiring parenteral therapy * No known HIV or AIDS * No uncontrolled blood pressure (BP), defined as systolic BP ≥ 150 mm Hg and/or diastolic BP ≥ 100 mm Hg * No uncontrolled or significant cardiovascular disease, including any of the following: * Myocardial infarction within the past 6 months * Uncontrolled angina within the past 6 months * New York Heart Association class II-IV congestive heart failure * Grade 3 cardiac valve dysfunction * Cardiac arrhythmia not controlled by medication * Stroke or transient ischemic attack within the past 6 months * Arterial thrombotic event of any type within the past 6 months * No significant or symptomatic vascular disease (e.g., aortic aneurysm, aortic dissection, or peripheral vascular disease) within the past 6 months * No decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy not corrected by conservative measures * No grade 3 bleeding esophageal or gastric varices within the past 2 months * Prior variceal bleeding allowed provided patient has undergone banding or sclerotherapy and there has been no evidence of bleeding for 2 months * No gastric varices ≥ grade 2 * No hemoptysis (i.e., ≥ ½ teaspoon of bright red blood per episode) within the past month * No evidence of bleeding diathesis or coagulopathy * No concurrent uncontrolled illness, including, but not limited to, a history of or current evidence of unexplained nephrotic syndrome or other severe illness/disease that would preclude study participation * No history of hypertensive crisis or hypertensive encephalopathy * No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months * No serious, non-healing wound, active ulcer, or untreated bone fracture * No significant traumatic injury within the past 28 days * No history of allergy to bevacizumab, erlotinib hydrochloride, sorafenib tosylate, or related compounds * No other primary malignancy within the past 5 years, except carcinoma in situ of the cervix or urinary bladder or nonmelanoma skin cancer * No mental incapacitation or psychiatric illness that would preclude study participation * Not incarcerated or compulsorily detained (i.e., involuntarily incarcerated) for treatment of either a psychiatric or physical illness (e.g., infectious disease) PRIOR CONCURRENT THERAPY: * Prior surgery, local ablation, trans-arterial hepatic artery embolization, or trans-arterial chemoembolization are allowed provided the lesion(s) have progressed since treatment OR there are additional measurable, untreated lesions present * No prior systemic therapy for HCC * No prior organ transplantation * More than 7 days since prior minor surgical procedures, fine needle aspirations, or core biopsies (excluding placement of a vascular access device) * More than 28 days since any prior therapy * More than 28 days since prior and no concurrent major surgical procedure or open biopsy * More than 28 days since prior and no concurrent participation in another experimental drug study * No other concurrent anticancer or antitumor therapy, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy * No other concurrent investigational agents * No concurrent warfarin (other types of anticoagulation allowed)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (6)

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90033-0804, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Columbia University/ New York Presbyterian Hospital

New York, New York, 10032, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Tennessee Oncology, PLLCat Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

Location

UVA Cancer Center

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Bevacizumab; Erlotinib Hydrochloride; Sorafenib

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; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Kate Anderton, MPH, CCRP
• Organization: Medical University of South Carolina

anderton@musc.edu

anderton@musc.edu

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: April 14, 2009
• First Posted: April 15, 2009
• Study Start: March 1, 2009
• Primary Completion: May 1, 2016
• Study Completion: February 1, 2017
• Last Updated: September 11, 2017
• Results First Posted: September 11, 2017

Record last verified: 2015-10

Locations

US (6)