A Study of Tarceva (Erlotinib) and Avastin (Bevacizumab) in Patients With Advanced or Metastatic Liver Cancer.

A Single Arm, Open Label Study of First Line Treatment With Tarceva Plus Avastin on Progression-free Survival in Patients With Advanced or Metastatic Liver Cancer

This single arm study evaluated the efficacy and safety of a combination of Tarceva and Avastin in patients with advanced or metastatic liver cancer. Patients were treated with Tarceva 150 mg po daily plus Avastin 5 mg/kg intravenous (iv) every 2 weeks. The anticipated time on study treatment was until disease progression, and the target sample size was <100 individuals.

Study Overview

• Status: Completed
• Conditions: Liver Cancer
• Intervention / Treatment: Drug: bevacizumab (Avastin); Drug: erlotinib (Tarceva)

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
• Philippines
  • Manila, Philippines, 1000
• Taiwan
  • Kueishan, Taiwan, 333
  • Tainan, Taiwan, 704
  • Taipei, Taiwan, 00112
  • Taipei, Taiwan, 106

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients, ≥ 18 years of age;
• advanced or metastatic liver cancer;
• ≥ 1 measurable lesion, not previously treated with local therapy within 4 weeks of enrollment.

Exclusion Criteria:

• prior or concomitant systemic anti-cancer treatment for advanced disease;
• patients at high risk of variceal bleeding;
• clinically significant cardiovascular disease;
• major surgery, open biopsy, or significant traumatic injury within 4 weeks of study start.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bevacizumab + erlotinib; Participants received bevacizumab (Avastin) 5 mg/kg intravenous (iv) on day 1 of each 2 week cycle plus erlotinib (Tarceva) 150 mg orally once a day until disease progression or unmanageable toxicity.	Drug: bevacizumab (Avastin); 5 mg/kg iv on day 1 of each 2 week cycle.; Drug: erlotinib (Tarceva); 150 mg orally (po) daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Progression-free Survival (PFS)	Percentage of participants who were alive and without documented progressive disease 16 weeks after their first dose of study drug. Diagnosis of Progressive Disease was made by objective criteria (RECIST criteria) on the target lesion(s), or by documenting, with Computerised Tomography/Magnetic Resonance Imaging (CT/MRI) scans, the presence of newly occurring lesion(s) arising outside the scanned areas of the target lesions. PD required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR). Analysis of tumor response was based on the best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST), which was defined as the best response recorded from the start of trial treatment until disease progression/recurrence (or death), taking as reference for progressive disease (PD) the smallest measurements recorded since the treatment started. CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. PD required at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	Event driven (median follow-up 12 months)
Disease Control Rate (DCR)	Disease Control Rate was defined as the percentage of participants with Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for at least 8 weeks by Response Evaluation Criteria in Solid Tumours (RECIST). CR was defined as the disappearance of all target lesions; for non-target lesions disappearance of lesions and normal tumour marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using as reference the Baseline sum LD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started; for non-target lesions persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.	Event driven (median follow-up 12 months)
Time to Tumor Progression	Time to tumor progression was defined as the time period in months from the start of study drug treatment to disease progression. Progressive disease required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	Event driven (median follow-up 12 months)
Progression-free Survival (PFS)	PFS was defined as the time period in months from the start of study drug treatment to the first of either progression or death. Progressive disease required at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	Event driven (median follow-up 12 months)
Overall Survival (OS)	OS was defined as the time period in months from the start of study drug treatment to death.	Event driven (median follow-up 12 months)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.	Up to 107 Weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: January 18, 2008
• First Submitted That Met QC Criteria: January 18, 2008
• First Posted (Estimate): January 31, 2008

Study Record Updates

• Last Update Posted (Estimate): July 14, 2014
• Last Update Submitted That Met QC Criteria: June 12, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Bevacizumab
• Other Study ID Numbers: ML21213