Clinical trial NCT00881751: Bevacizumab and Erlotinib or Sorafenib as First-Line Therapy in Treating Patients With Advanced Liver Cancer
Official title: A Randomized Open-Label Multi-Institution Phase II Study of the Combination of Bevacizumab and Erlotinib Compared to Sorafenib in the First-Line Treatment of Patients With Advanced Hepatocellular Carcinoma (HCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Cancer
Keywords: adult primary hepatocellular carcinoma
advanced adult primary liver cancer
recurrent adult primary liver cancer
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2009-04-15
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 116
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: OBJECTIVES:

Primary

* To estimate the overall survival in patients with advanced hepatocellular carcinoma treated with bevacizumab and erlotinib hydrochloride vs sorafenib tosylate.

Secondary

* To estimate the event-free survival and tumor response rate of these patients.
* To evaluate the safety and tolerability of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28.
* Arm II: Patients receive oral sorafenib tosylate twice daily on days 1-28. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days and then every 3 months for 1 year.

Eligibility criteria: 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)

Primary outcomes:
measure: Overall Survival
timeFrame: from date of day 1 until the date of death
Secondary outcomes:
measure: Event-free Survival
timeFrame: From the time of randomization until progression, withdrawal due to toxicity or any other clinical event requiring withdrawal from the study.
measure: Number of SAEs Experienced
timeFrame: From day 1 of drug administration until 30 days after the last dose of study drug.
measure: Response Rate
timeFrame: From day 1 drug administration until 30 days after the last dose of study drug.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: New York
country: United States
facility: Columbia University/ New York Presbyterian Hospital
state: New York
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology, PLLCat Sarah Cannon Cancer Center
state: Tennessee
city: Charlottesville
country: United States
facility: UVA Cancer Center
state: Virginia
Study officials:
References: