Ridaforolimus With Cetuximab: Adv Non-Small Cell Lung, Colorectal, Head & Neck Cancer
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Ridaforolimus
Intervention description: Ridaforolimus 20 Daily, 5 days each week, (Mon-Fri) on a 28 day cycle
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small Cell Lung Cancer

Summary:

      The main purpose of this study is to evaluate the best dose, safety and side effects of
      ridaforolimus when given with cetuximab for patients with head and neck, lung and colon
      cancer that has progressed after initial therapy. A second purpose of this study is to gain
      preliminary information on whether the combination of ridaforolimus and cetuximab is helpful
      in treating patients with advanced head and neck cancer
    

Eligibility criteria:

        Inclusion Criteria

          -  Histologically or cytologically advanced head and neck cancer, NSCLC or colorectal
             cancer (wild-type KRAS) in whom there is no curable option and have progressed after
             at least one regimen for advanced disease. Once the final dose level has been
             determined, only patients with advanced lung cancer who fail at least one line of
             chemotherapy will be eligible to be accrued to the 13 patient expanded cohort. *** As
             of July 7, 2011 the final dosing level has been determined and the next cohort of
             patients with advanced lung cancer will be enrolled**

          -  Patient has measurable disease by protocol-specific RECIST criteria.

          -  A minimum of 4 weeks has elapsed between prior chemotherapy and day 1 of study
             treatment.

          -  A minimum of 14 days has elapsed since prior kinase inhibitor therapy or radiotherapy,
             and a minimum of 4 weeks has elapsed since prior bevacizumab.

          -  No prior exposure to an mTOR inhibitor. Prior cetuximab exposure is allowed.

          -  ECOG performance status 0-1

          -  Required initial lab values: Hemoglobin ≥9.0 g/dL, absolute neutrophil count
             ≥1,500/mm3, platelet count ≥100,000/mm3, total bilirubin ≤1.5 times the upper limit of
             normal, AST or ALT <3 times the upper limit of normal, serum albumin ≥2.5 g/dL, serum
             cholesterol ≤350 mg/dL, triglycerides ≤400 mg/dL, creatinine <1.5 times the upper
             limit of normal, or a calculated creatinine clearance ≥50 ml/min.

          -  Age ≥18 years

          -  Those of child-bearing potential must agree to use of effective method of
             contraception

          -  Patients must have the ability to understand and give written informed consent

        Exclusion criteria:

          -  Patient is known to have active brain metastases. Patients with previously treated
             brain metastases that are stable for >3months are eligible if a current brain MRI
             (within 28 days of day 1 of study treatment) shows no edema or evidence of progression
             compared to a prior study at least 3 months ago.

          -  Patient is currently participating or has participated in a study with an
             investigational anticancer treatment or device within 30 days or 5 half lives of the
             investigational compound (whichever is greater) of initial dosing with study drug.

          -  Patient has previously received rapamycin or rapamycin analogs, including
             ridaforolimus, everolimus, or temsirolimus.

          -  Patient is receiving corticosteroids administered at doses greater than those used for
             normal replacement therapy.

          -  Patient has a history of prior invasive malignancy except for basal cell carcinoma of
             the skin within the past two years or who is deemed at low risk for recurrence by his
             treating physician.

          -  Patient has known severe hypersensitivity to macrolide antibiotics (ie:
             clarithromycin, erythromycin, or azythromycin).

          -  Patient has NYHA Class III or IV congestive heart failure or any other significant
             history of cardiac disease including: myocardial infarction within the last 6 months;
             ventricular arrhythmia or acute congestive heart failure within the last 3 months;
             uncontrolled angina or uncontrolled hypertension.

          -  Patient is known to be HIV positive or has a known history of Hepatitis B or C.

          -  Patient has a psychiatric disorder that would interfere with cooperation with the
             requirements of the trial, is a regular user of illicit drugs (including "recreational
             use"), or has a recent history (within the last year) of drug or alcohol dependence.

          -  Patient is pregnant or breastfeeding, or expecting to conceive within the projected
             duration of the study.

          -  Patient has an active infection requiring intravenous antibiotics.

          -  Patient has a requirement for concurrent treatment with medications that are strong
             inducers or inhibitors of cytochrome P450 (CYP3A) (see Appendix). Patients should
             discontinue these medications for at least 2 weeks prior to the first dose of
             ridaforolimus. Concomitant medications that are metabolized by CYP3A are allowed
             (e.g., simvastatin or atorvastatin)