- Evaluate the response rate in patients with previously untreated cancer of unknown primary treated with the combination of carboplatin, paclitaxel, and everolimus.
- Assess time to progression, overall survival, duration of response, and time to treatment failure in patients treated with this regimen.
- Determine adverse events of this regimen in these patients.
- Perform descriptive correlative studies to determine response of specific tumor types, identified by the Origin-FFPE test, to this regimen.
OUTLINE: This is a multicenter study.
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive oral everolimus once daily on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients' tumor tissue samples from the most recent biopsy are analyzed for correlative studies, including gene expression profiling by Origin-FFPE test.
After completion of study therapy, patients are followed up every 3 months until disease progression, and then every 6 months for up to 3 years.
- 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
- 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
Last updated: 01/20/2013
NCT ID: NCT00936702