Efficacy and Safety Study of Bevacizumab and Erlotinib to Treat Primary Liver Cancer That Cannot be Removed By Surgery

• Status: Completed
• Trial end date: 2011-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective will be to assess progression-free survival (PFS) measured at 16 weeks following initiation of therapy with the combination of Avastin and erlotinib in patients with unresectable hepatocellular carcinoma (HCC). Progression-free survival is defined as the time from initiation of therapy until documented disease progression or death.

Secondary objectives include: response rate, median and overall survival, toxicity and tolerability, and to ascertain whether there is any correlation of response with prior treatment status and underlying HCC risk factor(s).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Genentech, Inc.
• Treatments: Antibodies; Antibodies, Monoclonal; Bevacizumab; Erlotinib Hydrochloride

Criteria

Inclusion Criteria:

1. Patients must have histologically confirmed hepatocellular carcinoma not amenable to curative resection.

2. Patients must have measurable disease as per the Response Evaluation Criteria In Solid Tumors (RECIST) criteria.

3. Patients are allowed to have had up to one prior systemic therapy, including chemotherapy or hormonal therapy. Previous treatments that are 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). Any prior therapy must have been completed >/= 30 days prior to study entry.

4. Eastern Cooperative Oncology Group (ECOG) performance status of

5. Childs-Pugh status of A or B.

6. Organ function: Absolute peripheral granulocyte count of >/= 1500 mm(3), platelet count of >/= 40,000 mm(3), hemoglobin >/= 10 gm/dL. Total bilirubinserum albumin >/= 2.5 gm/dL; transaminases up to 5 times the upper limit of institutional normal; and prothrombin time prolonged not more than 3 seconds greater than institutional normal, once attempts to correct a prolonged PT have been made. Patients who require full dose anticoagulation, who are otherwise eligible for this trial, are allowed to have an appropriately prolonged International Normalized Ratio (INR).

7. Negative 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.

8. Fertile men and women must agree to use adequate contraception prior to study entry and for the duration of study participation.

9. Age >/= 18 years. The agents Avastin 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.

Exclusion Criteria:

1. Patients who have had prior vascular endothelial growth factor (VEGF) - or epidermal growth factor receptor (EGFR)-targeted therapy.

2. History of prior malignancy other than non-melanoma skin cancer or cervical dysplasia, within five years prior to protocol entry.

3. History of ruptured Hepatocellular carcinoma (HCC) lesion, or HCC lesion with large necrotic areas seen on conventional imaging studies, as determined by the Principal Investigator.

4. Abnormalities of the cornea based on history (eg dry eye syndrome, Sjogren's syndrome) or congenital abnormality (eg Fuch's dystrophy).

5. Gastrointestinal disease resulting in an inability to take oral medication or a requirement for intravenous hyperalimentation.

6. Uncontrolled intercurrent illness including but not limited to: ongoing or active infection requiring parenteral therapy; known HIV disease, New York Heart Association Class II or greater heart failure, cardiac arrhythmia not controlled by medication, uncontrolled psychiatric illness, a history of or current evidence of unexplained nephrotic syndrome, history of uncontrolled hypertension (defined as systolic blood pressure >140 and/or diastolic blood pressure > 90) that is refractory to medical management.

7. Patients may not have received any other investigational agents nor have received any systemic chemotherapy

8. History of significant gastrointestinal bleeding requiring procedural intervention (eg variceal banding, TIPS procedure, arterial embolization) within 3 months prior to study enrollment. Patients at risk for varices (based on the following: known history of esophageal or gastric varices; evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices) will be screened for esophageal varices. If varices are identified that require intervention (banding),patient will not be eligible until varices adequately treated.

9. History of myocardial infarction or unstable angina within 6 months.

10. History of stroke within 6 months.

11. Any prior history of hypertensive crisis or hypertensive encephalopathy.

12. Significant or symptomatic vascular disease (e.g., aortic aneurysm, aortic dissection, or peripheral vascular disease).

13. Evidence of clinically significant (Common Toxicity Criteria (CTC) Grade 3 or 4) venous or arterial thrombotic disease within previous 6 months.

14. Current evidence of bleeding disorder or coagulopathy that is not controlled by conservative medical management.

15. Known presence or clinical evidence of central nervous system or brain metastases.

16. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study.

17. Minor surgical procedures, fine needle aspirations or core biopsies, excluding placement of a vascular access device, within 7 days prior to Day 0.

18. Pregnant (positive pregnancy test) or lactating.

19. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0.

20. Serious, non-healing wound, ulcer, or bone fracture.

21. Proteinuria at screening as demonstrated by either: Urine protein:creatinine (UPC) ratio >/= 1.0 at screening, or: Urine dipstick for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrateto be eligible).

22. Known hypersensitivity to any component of Avastin

23. Inability to comply with study and/or follow-up procedures.

24. Radiographic evidence of major tumor thrombus in the vena cava.