Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor

  • Histologically confirmed metastatic kidney cancer, neuroendocrine carcinoma, melanoma, or non-small cell lung cancer (cohort 2B)
• Unresectable disease
• No known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
• Tumor amenable to biopsy (cohort 2A)
• No lymphoma
• No CNS metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• ANC ≥ 1,500/μL
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 100,000/μL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 3 times ULN (5 times ULN if liver involvement)
• Creatinine ≤ 1.5 times ULN
• INR ≤ 1.4 (cohort 2A)
• Urine protein negative by dipstick OR total urine protein ≤ 500 mg and measured creatinine clearance ≥ 50mL/min by 24-hour urine collection
• Willing to return to Mayo Clinic Rochester for follow-up visits
• Willing to provide blood specimens for required translational research studies (cohorts 2A and 2B)
• Willing to undergo brachial artery ultrasound measurements (cohorts 2A and 2B)
• Willing to undergo dynamic contrasted-enhanced MRI (cohort 2A)
• No contraindications for dynamic contrasted-enhanced MRI (e.g., MRI-incompatible metallic implants or prosthetic heart valves [e.g., pacemakers]) (cohort 2A)
• No uncontrolled infection
• No New York Heart Association class III or IV heart disease
• No uncontrolled hypertension, labile hypertension, or history of poor compliance with antihypertensive medication
• No active bleeding diathesis
• No seizure disorder

• No concurrent, severe and/or uncontrolled medical condition that would compromise study participation or pose as unnecessary risk to the patient, including, but not limited, any of the following:

  • Unstable angina
  • Myocardial infarction within the past 6 months
  • Serious uncontrolled cardiac arrhythmia
  • Uncontrolled diabetes
  • Interstitial pneumonia or extensive, symptomatic interstitial fibrosis of the lung
  • QTc > 500 msec

• No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of vatalanib, including any of the following:

  • Ulcerative disease
  • Uncontrolled nausea, vomiting, or diarrhea
  • Malabsorption syndrome
  • Bowel obstruction
  • Inability to swallow the tablets
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

• More than 3 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas) and recovered
• More than 2 weeks since prior immunotherapy or biological therapy
• More than 4 weeks since prior investigational therapy

• More than 4 weeks since prior full-field radiotherapy

  • Full-field radiotherapy encompasses the entire area of known disease involvement and surrounding uninvolved, at-risk areas (e.g., sub-total nodal [mantle and upper abdomen] or total nodal irradiation)

• More than 2 weeks since prior limited-field radiotherapy

  • Limited-field radiotherapy is restricted to treating only the known areas of clinical disease (e.g., involved-field therapy for lymphoma)
• More than 4 weeks since prior major surgery (i.e., laparotomy)*
• More than 2 weeks since prior minor surgery*
• Prior anti-VEGF therapy allowed
• No prior radiotherapy to > 30% of the bone marrow
• No concurrent anticoagulant therapy except heparin for deep venous thrombosis prophylaxis
• No other concurrent chemotherapy, immunotherapy, radiotherapy, or ancillary therapy considered investigational (e.g., utilized for a non-FDA-approved indication and in the context of a research investigation)
• No concurrent chronic treatment with proton pump inhibitors (e.g., omeprazole or lansoprazole) or H2 antagonists (e.g., ranitidine or famotidine)
• No concurrent prophylactic colony-stimulating factors NOTE: *Insertion of a vascular access device is not considered major or minor surgery