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A Phase II Study of the Combination of Bevacizumab and Erlotinib in Patients With Unresectable Hepatocellular Carcinoma


Phase 2
18 Years
N/A
Not Enrolling
Both
Hepatocellular Carcinoma, Liver Cancer

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Trial Information

A Phase II Study of the Combination of Bevacizumab and Erlotinib in Patients With Unresectable Hepatocellular Carcinoma


Liver cancer growth may be affected by a protein in the body called "vascular epidermal
growth factor" (VEGF). A drug that blocks VEGF may be an effective treatment for liver
cancer. Avastin is designed to block VEGF. Erlotinib hydrochloride is an investigational
drug believed to work on cancer cells by affecting epidermal growth factor receptor (EGFR),
a protein that is important to cancer growth.

If the screening evaluations show you are eligible to take part in the study, you may begin
treatment. You will receive treatment in 28-day periods called "cycles". Treatment will be
given on an outpatient basis. Because this is a research study, the Avastin infusion must
be given every time at M. D. Anderson. Because erlotinib hydrochloride is given by mouth,
you may take it away from M. D. Anderson.

You will receive Avastin through a needle in a vein on Days 1 and 15 of each cycle. The
first dose of Avastin will be given over about 90 minutes. If you do not have a reaction
(such as fever/chills), the next dose will be given over about 60 minutes. If again no
reaction occurs, each dose after that will be given over about 30 minutes. If you
experience a reaction to the Avastin infusion, you may be given acetaminophen (such as
Tylenol) by mouth and/or an antihistamine by vein over 30 minutes before each dose to help
decrease the risk of further reactions.

You will take erlotinib hydrochloride tablets by mouth every day. It is recommended that
erlotinib hydrochloride be taken in the morning with a glass of water. Erlotinib
hydrochloride should be taken at least 1 hour before or 2 hours after you have any food,
grapefruit juice, vitamins, iron supplements, or other non-prescription medicines.

Before each new cycle of study treatment, you will have urine collected, and blood will be
drawn (about 3 tablespoons) for routine blood tests and to check your blood clotting. You
will be asked questions about any side effects you may have had and about any medications
you are currently taking or have taken since you last saw the study doctor. You will have a
complete physical exam, including measurements of vital signs and weight. You will be asked
about your ability to perform everyday tasks.

You will also have CT and/or MRI scans of the tumor(s) every 8 weeks. Additional tests may
be done during the study if your doctor feels it is necessary for your care. All testing
and evaluations must be done at M. D. Anderson.

If you experience severe side effects, treatment may be delayed, stopped, or you may receive
smaller doses of the treatment. You may continue to receive study treatment unless the
disease gets worse, the side effects are too severe, you decide not to take part any longer,
or your doctor decides it is in your best interest to stop treatment. There is no maximum
number of cycles that you can receive.

When you stop study treatment, you will be asked to have tests and evaluations done at an
end-of-study visit. You will have urine collected, and blood will be drawn (about 3
tablespoons) for routine blood tests and to check your blood clotting. You will be asked
questions about any side effects you may have had and about any medications you are
currently taking or have taken since you last saw the study doctor. You will have a complete
physical exam, including measurements of blood pressure, pulse, temperature, and weight.
You will be asked about your ability to perform everyday tasks. You will also have CT
and/or MRI scans of the abdomen and pelvis to check on your cancer.

Once you stop receiving study treatment, the study doctor or nurse will continue to check
how you are doing, either in the clinic or by telephone if you stop coming to M. D.
Anderson, every 3 months for the rest of your life.

This is an investigational study. Erlotinib hydrochloride is approved by the FDA for
treatment of lung cancer, but it is not approved for liver cancer, so its use is considered
experimental in this study. Avastin is approved by the FDA for treatment of colon and
rectal cancer, but it is not approved for the treatment of liver cancer, so its use is
considered experimental in this study. Up to 60 participants will take part in this study.
All will be enrolled at M. D. Anderson.


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 bilirubin serum 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 demonstrate to 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free Survival (PFS) Rate

Outcome Description:

Progression free survival (PFS) at 16 weeks of treatment with the combination of Avastin and erlotinib where participant said to be failure free at 16 weeks if they are alive, and their disease has not progressed. PFS Rate is number of participants with PFS at 16 weeks out of total participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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.

Outcome Time Frame:

Baseline to 16 weeks

Safety Issue:

No

Principal Investigator

Ahmed Kaseb, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2004-0874

NCT ID:

NCT00242502

Start Date:

October 2005

Completion Date:

October 2011

Related Keywords:

  • Hepatocellular Carcinoma
  • Liver Cancer
  • Hepatocellular Carcinoma
  • Liver Cancer
  • Bevacizumab
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
  • Erlotinib Hydrochloride
  • OSI-774
  • Tarceva
  • Erlotinib
  • Avastin
  • Carcinoma
  • Liver Neoplasms
  • Carcinoma, Hepatocellular

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030