RAD001, Cisplatin and Concurrent Radiation for Locally Advanced, Inoperable Head and Neck Cancer
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Intervention: RAD001(Afinitor)
Intervention description: Rad001 in combination withCisplatin and Concurrent RT
Intervention MeSH terms: Everolimus
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck Cancer; Advanced Inoperable Head & Neck Cancer

Summary:

      The purpose of this study is to determine if RAD001, to a maximum dose of 10 mg/day, can be
      safely administered with cisplatin, and concurrent radiotherapy, for patients with locally
      advanced, inoperable, squamous cell carcinoma of the head and neck.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically (histologically or cytologically) proven (from primary lesion and/or
             lymph nodes) diagnosis of squamous cell carcinoma of the oral cavity, oropharynx,
             hypopharynx, or larynx;

          -  Stage III or IV disease. Patients are unresectable or resection would produce severe
             impairment or disfiguration.

          -  Appropriate stage for protocol entry, including no distant metastases, based upon the
             following minimum diagnostic workup:

          -  History/physical examination within 4 weeks prior to registration

          -  Chest x-ray (or Chest CT scan or PET/CT scan) within 6 weeks prior to registration.

          -  CT scan, Pet CT, or MRI of the head and neck (of the primary tumor and neck nodes).

          -  Zubrod Performance Status 0-1;

          -  Age > 18;

          -  Adequate bone marrow function, defined as ANC > 1,500 cells/ul and Platelets > 100,000
             cells/ul and Hgb > 9mg/dl.

          -  Bilirubin < 1.5x upper limit of normal, (For patients with Gilbert's disease as the
             sole cause of elevated bilirubin, they are eligible if the direct bilirubin is < than
             1.5x upper limit of normal)

          -  AST or ALT < 2.5x the upper limit of normal.

          -  Adequate renal function, defined as follows:

          -  Creatinine clearance (CC) ≥ 50 ml/min within 2 weeks prior to registration determined
             by:

             24-hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140 - age) x
             (wt in kg)] [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male)

          -  INR and PTT < 1.5 x uln. (Anticoagulation is allowed if target INR < 1.5 on a stable
             dose of warfarin or a stable dose of LMW heparin for > 2 weeks prior to starting
             treatment.)

          -  Pregnancy test within 7 days prior to administration of RAD001for women of
             childbearing potential.

          -  Women of childbearing potential and male participants must agree to use a medically
             effective means of birth control throughout their participation in the treatment phase
             of the study (until at least 60 days following the last study treatment); If barrier
             contraceptives are being used, these must be continued throughout the trial by both
             sexes. Hormonal contraceptives are not acceptable as a sole method of contraception.
             (Women of childbearing potential must have a negative urine or serum pregnancy test
             within 7 days prior to administration of RAD001)

          -  Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x
             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 and values have
             been rechecked.

          -  EKG within 6 weeks of study entry

          -  Signed informed consent

        Exclusion Criteria:

          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 3years.

          -  Patients with simultaneous primaries or bilateral tumors are excluded. Patients with
             nasopharyngeal cancer and unknown primaries are excluded.

          -  Gross total excision (e.g., by tonsillectomy) of the primary tumor; however, partial
             removal of the tumor to alleviate an impending airway obstruction does not make the
             patient ineligible.

          -  Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
             different cancer is allowable.

          -  Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields.

          -  Initial surgical treatment, excluding diagnostic biopsy of the primary site or nodal
             sampling of neck disease; radical or modified neck dissection is not permitted.

          -  Severe, active co-morbidity, defined as follows:

          -  Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable
             angina, uncontrolled congestive heart failure.

          -  Transmural myocardial infarction within the last 6 months;

          -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time of
             registration;

          -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
             requiring hospitalization or precluding study therapy at the time of registration
             defined as oxygen saturation that is < 88% at rest on room air.

          -  Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note,
             however, that HIV testing is not required for entry into this protocol. The need to
             exclude patients with AIDS from this protocol is necessary because the treatments
             involved in this protocol may be significantly immunosuppressive. Protocol-specific
             requirements may also exclude immuno-compromised patients.

          -  Any uncontrolled condition, which in the opinion of the investigator, would interfere
             in the safe and timely completion of study procedures;

          -  Pregnant or lactating women or women of childbearing potential and men who are
             sexually active and not willing/able to use medically acceptable forms of
             contraception ; this exclusion is necessary because the treatment involved in this
             study may be significantly teratogenic.

          -  Prior allergic reaction to the study drug(s) involved in this protocol;

          -  Patients receiving chronic, systemic treatment with corticosteroids or another
             immunosuppressive agent. Topical or inhaled corticosteroids are allowed.

          -  Patients should not receive immunization with attenuated live vaccines within one week
             of study entry or during study period

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled
             nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

          -  Patients with an active, bleeding diathesis or serum pregnancy test within 7 days
             prior to administration of RAD001)

          -  Patients who have received prior treatment with an mTOR inhibitor (sirolimus,
             temsirolimus, everolimus).

          -  Patients currently receiving anticancer therapies or who have received anticancer
             therapies within 4 weeks of the start of study drug (including chemotherapy, radiation
             therapy, antibody based therapy etc)

          -  Patients who have had a major surgery or significant traumatic injury within 4 weeks
             of the start of study drug, patients who have not recovered from the side effects of
             any major surgery (defined as requiring anesthesia) or patients that may require major
             surgery during the course of the study.

          -  Prior treatment with any investigational drug within the preceding 4 weeks.

          -  History of noncompliance to medical regeimens.

          -  Patients unwilling to or unable to comply with the protocol.