A Phase II Study of Carboplatin (CBDCA), Paclitaxel (TAXOL), and Everolimus (RAD001) in Previously Untreated Patients With Measurable Disease With Cancer of Unknown Primary (CUP)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed diagnosis of 1 of the following:

- Metastatic adenocarcinoma

- Poorly differentiated non-small cell carcinoma

- Poorly differentiated squamous cell carcinoma

- Patients with biopsy proven TTF-1 positive tumor who do not have clinical evidence
for either lung or thyroid cancer (e.g., a dominant lung mass) are still eligible

- Adequate FFPE tissue samples available

- Measurable disease defined as ≥ 1 lesion whose longest diameter can be accurately
measured as ≥ 2.0 cm by conventional techniques OR as ≥ 1.0 cm to ≤ 2 cm by spiral CT
scan

- Disease that has received prior radiotherapy for palliative reasons not
considered measurable disease

- No untreated brain metastases

- Patients with treated, stable brain metastases for ≥ 12 weeks prior to study
entry allowed

PATIENT CHARACTERISTICS:

- ECOG performance status of 0-2

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL

- Total bilirubin normal (≤ 2 times upper limit of normal [ULN] in presence of liver
metastasis)

- AST ≤ 2.5 times ULN (≤ 5 times ULN in presence of liver metastasis)

- Creatinine ≤ 1.25 times ULN OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must agree to use effective contraception

- Willing to undergo another biopsy if additional tissue sample is needed

- No co-morbid systemic illnesses or other severe concurrent disease that, 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

- No immunocompromised patients including patients known to be HIV positive

- No uncontrolled intercurrent illness including, but not limited to, the following
conditions:

- Ongoing or active infection (acute or chronic)

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Severely impaired lung function

- Uncontrolled diabetes as defined by fasting serum glucose > 1.5 times ULN

- Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent
hepatitis)

- Psychiatric illness and/or social situations that would limit compliance with
study requirements

- More than 5 years since diagnosis of other malignancy except for non-melanotic skin
cancer or carcinoma in situ of the cervix

- No impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of everolimus (e.g., ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
resection)

- No active bleeding diathesis

- No known HIV positivity

- No inoculation with live attenuated vaccines ≤ 2 weeks prior to registration

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Concurrent bisphosphonates allowed

- No prior chemotherapy for this cancer

- No prior radiotherapy to > 25% bone marrow

- Prior radiotherapy for palliative reasons for this cancer allowed

- No major surgery within the 4 past weeks

- Diagnostic laparoscopy (without other intervention) and/or biopsies (needle
aspirate, core biopsy, open biopsy, etc.) are not considered major surgery

- No investigational agent within the past 4 weeks that would be considered treatment
for the primary neoplasm

- No concurrent chronic systemic treatment with corticosteroids or another
immunosuppressive agent

- Topical or inhaled corticosteroids allowed

- No concurrent enzyme-inducing anti-convulsants or other strong inducers or strong
inhibitors of CYP3A4 (e.g., carbamazepine, phenytoin, phenobarbital, primidone,
rifabutin, rifampin, or St. John wort)

- No concurrent warfarin (coumadin) except for low-molecular weight heparin use

- No concurrent grapefruit, Seville oranges, or star fruit or their juices

- No other concurrent investigational therapy

- No other concurrent anticancer agents