Phase I Trial of RAD001 and Gemcitabine for Patients With Solid Tumors Refractory to Standard Therapy

Inclusion Criteria

Inclusion:

- Histologic proof of cancer that is now unresectable and refractory to or refused all
standard treatment for the disease

- Cohort II (MTD) Only: Patients with histologic proof of metastatic cholangiocarcinoma
or gallbladder carcinoma who have not had previous treatment for metastatic disease
or who received gemcitabine >= 6 months ago as part of adjuvant therapy

- Please contact study investigator and/or consult protocol document for specific
details on laboratory criteria

- ECOG Performance Status (PS) 0, 1 or 2

- Ability to provide informed consent

- Willingness to return to Mayo Clinic Rochester for follow up

- Life expectancy >= 12 weeks

- Women of childbearing potential only: Negative serum pregnancy test done =< 7 days
prior to registration

Exclusion:

- Known standard therapy for the patient's disease that is potentially curative or
definitely capable of extending life expectancy

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Clinically significant cardiac disease, especially history of myocardial infarction
=< 6 months, or congestive heart failure (NYHA classification III or IV) requiring
use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

- Patients taking strong inhibitors or inducers of CYP3A4

- Prior therapy with RAD001

- Any of the following prior therapies: chemotherapy =< 4 weeks prior to registration,
mitomycin C/nitrosoureas =< 6 weeks prior to registration, immunotherapy =< 4 weeks
prior to registration, biological therapy =< 4 weeks prior to registration, radiation
therapy =< 4 weeks prior to registration, radiation to > 25% of bone marrow prior to
registration

- Failed to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment

- CNS metastases that are not stable for at least 4 weeks prior to registration based
on imaging, clinical assessment, and use of steroids

- Uncontrolled brain or leptomeningeal metastases, including patients who continue to
require glucocorticoids for brain or leptomeningeal metastases

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
considered investigational (utilized for a non-FDA-approved indication and in the
context of a research investigation)

- Co-morbid systemic illnesses or other severe concurrent disease which, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens

- Immunocompromised patients (other than that related to the use of corticosteroids)
including patients known to be HIV positive

- Current active other malignancy, except non-melanoma skin cancer or carcinoma-in-situ
of the cervix

- If there is a history of prior malignancy, they must not be receiving other specific
treatment (other than hormonal therapy) for their cancer - 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)

- Severely impaired lung function (i.e., FEV1 < 1 liter)

- Prophylactic use of colony-stimulating factors during the study