Patient case: 48-year-old male with Pancreatic cancer. Genetic variant: CDK6 Amplification. Other conditions: None.

Clinical trial: Erlotinib Prior to Surgery in Patients With Head and Neck Cancer

Summary: The goal of this clinical research study is to learn the effects of the standard dose of erlotinib and the higher dose of erlotinib on biomarker levels in patients with head and neck cancer. Biomarkers are chemical "markers" in the blood and/or tissue that may be related to your response to the study drug. The safety of the drug will also be studied.
  Objectives:
  To determine the molecular effects and safety of erlotinib 150 mg/day (standard dose) and 200 mg/day or 300 mg/day (high-dose) in patients with head and neck cancer who are planned for surgery.
  Primary Objective:
  To determine the effects of erlotinib 150 mg/day (standard dose) and 200 mg/day or 300 mg/day (high-dose) on the phosphorylation of AKT protein downstream from EGFR.
  Secondary Objectives:
  1. To assess the safety and tolerability of erlotinib 150 mg/day (standard dose) and 200 mg/day or 300 mg/day (high-dose).
  2. To correlate the effects of erlotinib on the phosphorylation of AKT with the immunohistochemical expression level of EGFR and the level of amplification of the EGFR gene as determined by fluorescent in situ hybridization (FISH).
  3. To evaluate the preliminary response rate with a short course of erlotinib.
  4. To evaluate changes in the activation status of proteins downstream from EGFR and other receptor tyrosine kinases and in markers of epithelial to mesenchymal transition.
  5. To evaluate changes in blood-based biomarkers.
  6. To evaluate the effects of a higher dose of erlotinib (300 mg/day) in current smokers.

Detailed description: The Study Drug:
  Erlotinib is designed to block the activity of a protein found on the surface of many tumor cells that may control tumor growth and survival. This may stop tumors from growing.
  Study Groups:
  If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to receive erlotinib at either the standard dose or the high dose. There is an equal chance of being assigned to either group. If you are assigned to the high dose group and you are a current smoker, you will receive an even higher daily dose of erlotinib. Both you and your study doctor will know which group you are in.
  Study Drug Administration:
  Group 1 will take 1 tablet of erlotinib once a day, every day leading up to surgery.
  Group 2 will take 2 tablets once a day, every day leading up to surgery. Depending on your assigned dose level, the 2 tablets may contain the same drug amount or 2 different drug amounts.
  Erlotinib should be taken at the same time of day, 1 hour before or 2 hours after a meal. Each dose should be taken with 8 ounces of water. You should not consume grapefruit or grapefruit juice while on this study.
  If you vomit after taking the medication, you can take another dose again, but only if the vomited tablet(s) can be seen and counted (in other words, they have not been digested yet).
  Study Visits:
  Every 2 weeks, you will have a study visit. The following tests and procedures will be performed:
  -  Your medical history will be recorded.
  -  You will have a physical exam, including measurement of your vital signs.
  -  Blood (about 2 teaspoons) will be drawn for routine tests.
  -  You will be asked about any side effects you may be experiencing.
  -  You will have a CT scan or MRI to check the status of the disease within 1 week before the surgery.
  Within one week before your surgery, you will also have blood (about 2-3 teaspoons) drawn to check your blood clotting function.
  Length of Study:
  You will be on study for at least 2-3 weeks up to the day before surgery. You may be on study for up to 8 weeks if there is a delay in surgery.
  After you have completed the study, you will have surgery to remove your tumor. During your surgery, a sample of your tumor tissue that is already being removed will be collected to check for biomarkers.
  Follow-up:
  Within 30 days after your surgery, you will be contacted by phone to be asked you about any side effects you have experienced. The phone call will last about 10 minutes.
  This is an investigational study. Erlotinib is FDA approved and commercially available for the treatment of non-small cell lung cancer and pancreatic cancer (first-line therapy in combination with gemcitabine). Its use in this study is investigational.
  Up to 55 patients will be enrolled in this study. All will be enrolled at M. D. Anderson.

Eligibility: Inclusion Criteria:
  1. Patients with histologically confirmed cancer of the head and neck. Patients with salivary gland tumors and squamous cell carcinomas of the skin are also eligible. (Note: Any patient with a diagnosis of aggressive squamous cell carcinoma of the skin and determined to be surgically resectable will be considered for eligibility. These patients are typically seen in the Head & Neck surgery clinic and decisions for study consideration will be based on consultations with the department of Head & Neck surgery.)
  2. The patient must have biopsy-accessible disease.
  3. Patients must be surgical candidates (either definitive or palliative setting).
  4. Patients may have received prior therapy including cytotoxic chemotherapy (e.g. platinum drugs and taxanes) and radiation therapy.
  5. Patients must have a performance score (ECOG) of 0-2.
  6. Patients should have adequate bone marrow function, as defined by peripheral granulocyte count of >/= 1,000/mm³, and a platelet count of >/= 50,000/mm³.Patients must have adequate liver function with a bilirubin </= 1.5 times the upper limit of normal (ULN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be </= 2 x the ULN and alkaline phosphatase must be </= 2 x ULN.
  7. Patients should have adequate renal function (serum creatinine </= 1.5 x ULN).
  8. Age >/= 18 years
  9. Ability to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of the study, in keeping with institutional policy
  10. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Childbearing potential will be defined as women who have had menses within the past 12 months,who have not had tubal ligation or bilateral oophorectomy. Should a woman become pregnant or suspect that she is pregnant while participating in this study,she should inform her treating physician immediately.The patient,if a man,agrees to use effective contraception or abstinence.
  Exclusion Criteria:
  1. Patients with prior exposure to small molecule tyrosine kinase inhibitors or EGFR-targeted antibodies within the past 6 months.
  2. Patients for whom, in the opinion of the treating surgeon, the administration of erlotinib would cause a deleterious delay in surgical treatment.
  3. Patients with uncompensated congestive cardiac failure.
  4. Patients with an organ allograft.
  5. Patients with a serious concurrent infection or illness including, but not limited to, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness that could limit compliance with study requirements.
  6. Female patients who are pregnant or breastfeeding
  7. Patients currently on chemotherapy, immunotherapy, or therapy with monoclonal antibodies or other investigational agents with anti-tumor activity

Relevance to patient case: not relevant