Trial of RAD001 and Erlotinib With Recurrent Head and Neck Squamous Cell Carcinoma
Condition: Head And Neck Cancer
MeSH terms: Carcinoma; Carcinoma, Squamous Cell
Intervention: Erlotinib; RAD001
Intervention description: One tablet (150 mg) by mouth every day of each 28 day study cycle.; 1 tablet (5 mg) by mouth every day of each 28 day study cycle.
Intervention MeSH terms: Everolimus; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck; Squamous Cell Carcinoma; RAD001; Erlotinib; Everolimus; OSI-774; Tarceva

Summary:

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

Eligibility criteria:

        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 mammilian target of rapamycin (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