Trial of RAD001 and Erlotinib With Recurrent Head and Neck Squamous Cell Carcinoma

The goal of this clinical research study is to learn if RAD001 in combination with Tarceva (erlotinib hydrochloride) can help to control HNSCC. The safety of this drug combination will also be studied.

The Study Drugs:

RAD001 is designed to stop cancer cells from multiplying. It may also stop the growth of new blood vessels that help tumor growth, and this may cause the tumor cells to die.

Erlotinib hydrochloride 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 Drug Administration:

If you are found to be eligible to take part in this study, you will take 1 RAD001 tablet and 1 erlotinib hydrochloride tablet every day of each 28 day study "cycle".

Both drugs should be taken at the same time, by mouth, with a cup (8 ounces) of water. You should take the drugs at least 1 hour before or 2 hours after eating. You should take the study drugs at around the same time each day. Your eating habits around the time you take the drugs should stay the same while you are on study. lf you vomit, you should not take another tablet until your next scheduled dose.

Tell your doctor if you have any side effects, as your dose(s) of study drug(s) may be lowered or stopped for a few days. You may be given drugs to help reduce the risk of side effects.

Study Visits:

On Day 1 (+/- 3 days) of each cycle, the following tests and procedures will be performed:

• You will have a complete physical exam, including measurement of your weight and vital signs.
• You will be asked about any drugs you may be taking and any side effects you may be having.
• Your performance status will be recorded.
• Blood (about 3 teaspoons) will be drawn for routine tests. If your doctor thinks it is needed, you may have to have these blood tests more often.

On Day 1 (+/- 3 days) of every evenly numbered cycle (Cycles 2, 4, 6, and so on), you will have a CT scan or MRI scan to check the status of the disease.

Length of Study:

You may continue to take the study drugs for as long as you are benefitting. You will be taken off study if the disease gets worse or if you have intolerable side effects.

End-of-Study Visit:

When you go off study for any reason, you will have an end-of-study visit. The following tests and procedures will be performed:

• Your medical history will be recorded.
• You will have a complete physical exam, including measurement of your weight and vital signs.
• You will be asked about any drugs you may be taking and any side effects you may be having.
• Your performance status will be recorded.
• Blood (about 3 teaspoons) will be drawn for routine tests.
• You will have a CT scan or MRI scan to check the status of the disease.

Follow-Up:

You will be called within 30 days after the end-of-study visit and asked how you are doing and about any possible side effects that you may have had. The call should take about 5 minutes.

This is an investigational study. RAD001 is FDA approved and commercially available for the treatment of certain types of breast cancer. Erlotinib hydrochloride is FDA approved and commercially available for the treatment of advanced non-small cell lung carcinoma (NSCLC) and advanced pancreatic cancer. The use of this drug combination for the treatment of HNSCC is investigational.

Up to 35 patients will take part in this study. All will be enrolled at MD Anderson.

• Drug: Erlotinib
  One tablet (150 mg) by mouth every day of each 28 day study cycle.
  Other Names:

  • OSI-774
  • Tarceva
• Drug: RAD001
  1 tablet (5 mg) by mouth every day of each 28 day study cycle.
  Other Name: Everolimus

Inclusion Criteria:

1. Histologically or cytologically confirmed squamous cell carcinoma of the head and neck
2. Patients that have failed one platinum-containing chemotherapy regimen with or without EGFR inhibitor and/or epidermal growth factor receptor (EGFR) inhibitor as systemic therapy for recurrent/metastatic disease. Prior investigational therapy (with the exclusion of mTOR inhibitor) allowed but at least 4 weeks must have elapsed with recovery from all toxicities
3. Patients who had prior induction or concurrent chemotherapy delivered as part of their primary treatment are eligible as long as they have completed primary therapy at least 6 months prior to study entry.
4. Patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
5. Age >/= 18 years
6. Minimum of two weeks since any major surgery or completion of radiation. Note: Patients may have received prior radiation therapy to tumor sites that will not be assessed for response, unless there is evidence of progression.
7. Completion of all prior systemic anticancer therapy for the treatment of recurrent/metastatic disease (adequately recovered from the acute toxicities of any prior therapy) at least 4 weeks prior to study entry
8. Eastern Cooperative Oncology Group (ECOG) performance status </= 2
9. Laboratory Values (within 14 days prior to administration of study drugs): Adequate bone marrow function as shown by: absolute neutrophil count (ANC) >/= 1.5 * 10^9/L, Platelets >/= 100 * 10^9/L, Hgb > 10 g/dL; Adequate liver function as shown by: serum bilirubin </=1.5 * upper limit of normal (ULN), and serum transaminases activity </= 3 * ULN. With the exception of serum transaminases (< 5 * ULN) if the patient has liver metastases
10. Continued from Inclusion # 9: Fasting serum cholesterol </= 300 mg/dL OR </= 7.75 mmol/L AND fasting triglycerides </= 2.5 * ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
11. Signed informed consent

Exclusion Criteria:

1. Prior treatment with any investigational drug within the preceding 4 weeks, concomitant chemotherapy, hormonal therapy, radiotherapy or immunotherapy, or therapy with agents otherwise used in treatment of cancer (for example, methotrexate for rheumatoid arthritis)
2. Chronic treatment with systemic steroids or another immunosuppressive agent. Steroids will not be allowed and should be discontinued 24 hours prior to initiation of treatment on protocol. An exception for replacement steroids prescribed for adrenal insufficiency will be allowed.
3. Patients should not receive immunization with attenuated live vaccines during study period or within one week of study entry
4. Patients with metastatic disease to the brain, unless treated and controlled and the patient is off steroids and/or antiepileptics for at least 3 weeks.
5. Other malignancies within the past 2 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
6. Patients with active skin, mucosa, ocular or gastrointestinal disorders grade > 1
7. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction, </= 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia
8. Continued from Exclusion #7: severely impaired lung function; uncontrolled diabetes as defined by fasting serum glucose >1.5x ULN; any active (acute or chronic) or uncontrolled infection/ disorders.; nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy; liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
9. A known history of HIV or AIDS-related illness or previous seropositivity for the virus
10. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study agents (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
11. Patients with any condition which impairs the ability to swallow study agent intact
12. Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin)
13. Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice an effective method of birth control. (Women of childbearing potential (WOCP) must have a negative urine or serum pregnancy test within 7 days prior to administration of study drugs). WOCP: A female of child bearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
14. (Continued from Exclusion # 13) Females must either commit to abstinence from heterosexual intercourse or use a barrier method of contraception. Oral, implantable, and injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Males must either commit to abstinence from heterosexual intercourse or use a barrier method of contraception.
15. Lack of resolution of all toxic manifestations of prior chemotherapy biologic therapy or radiation therapy.
16. Patients who have received prior treatment with an mTor inhibitor.
17. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients
18. Patients with psychiatric illness or confusional status that may impair the patient's understanding of the informed consent
19. Patients unwilling to or unable to comply with the protocol
20. Patients with any condition which impairs the ability to swallow study agent intact

• Novartis
• OSI Pharmaceuticals