• Maximum tolerated dose of sunitinib malate [ Designated as safety issue: Yes ]
• Toxicity [ Designated as safety issue: Yes ]
• Response [ Designated as safety issue: No ]
• Survival [ Designated as safety issue: No ]

• Maximum-tolerated dose of sunitinib malate [ Designated as safety issue: Yes ]
• Toxicity [ Designated as safety issue: Yes ]
• Response [ Designated as safety issue: No ]
• Survival [ Designated as safety issue: No ]

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib together with hydroxychloroquine may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of sunitinib when given together with hydroxychloroquine in treating patients with advanced solid tumors that have not responded to chemotherapy.

OBJECTIVES:

• To determine the maximum tolerated dose of sunitinib malate, an oral tyrosine kinase inhibitor with antiangiogenic activity, that inhibits VEGFR2, c-kit, and PDGFR, in combination with hydroxychloroquine, an inhibitor of autophagy, in patients with advanced solid tumors that are refractory to standard chemotherapy.

OUTLINE: This is a dose-escalation study of sunitinib malate.

Patients receive oral sunitinib malate once daily and oral hydroxychloroquine twice daily on days 1-28. Treatment repeats every 42 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 1 year.

• Drug: hydroxychloroquine
• Drug: sunitinib malate

DISEASE CHARACTERISTICS:

• Histologically confirmed cancer

• Must have undergone treatment with ≥ 1 regimen of standard therapy (i.e., cytotoxic chemotherapy, an oral targeted agent, or immunotherapy)

  • Prior therapy with sunitinib malate allowed
  • Concurrent hormonal therapy for prostate cancer allowed
• Measurable disease according to RECIST criteria

• No diagnosis or history of CNS disease (i.e., primary brain tumor, malignant seizures, untreated CNS metastases, or carcinomatous meningitis)

  • Patients with brain metastases that have been treated and stable for > 4 weeks are allowed

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute granulocyte count > 1,500/mm³
• Platelet count > 100,000/mm³
• Serum creatinine < 2.0 times upper limit of normal (ULN) OR creatinine clearance > 30 mL/min
• Total bilirubin < 1.5 times ULN
• SGOT and SGPT < 2.5 times ULN
• LVEF > 50% by MUGA scan
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of any condition (social or medical) that, in the opinion of the investigator, might interfere with the patient's ability to comply with the protocol or pose additional or unacceptable risk to the patient
• No serious concomitant systemic disorder that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
• No second primary malignancy, except most in situ carcinoma (e.g., adequately treated nonmelanoma carcinoma of the skin) or other malignancy treated at least 5 years previously with no evidence of recurrence
• No active clinically significant infection requiring antibiotics
• No hypertension that cannot be controlled by medications (diastolic BP > 100 mm Hg despite optimal medical therapy)
• No pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be maintained in the normal range with medication

• No ongoing grade 2 (NCI CTCAE v3.0) ventricular cardiac dysrhythmias

  • No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation > 3 beats in a row)
  • No ongoing atrial fibrillation
• QTc interval ≤ 500 msec on baseline EKG

• None of the following conditions within the past 6 months:

  • Myocardial infarction
  • Symptomatic coronary artery disease (severe or unstable angina)
  • Artery bypass graft
  • Uncontrolled arrhythmias
  • Symptomatic congestive heart failure
  • Cerebrovascular accident or transient ischemic attack
  • Pulmonary embolus
• No known HIV positivity
• No psoriasis or porphyria
• No known prior hypersensitivity to sunitinib or hydroxychloroquine or any of their components
• No known hypersensitivity to 4-aminoquinoline compound
• No retinal or visual field changes from prior 4-aminoquinoline compound use
• No known G-6P deficiency
• No known gastrointestinal pathology that would interfere with drug bioavailability
• No clinically significant bleeding or clotting disorder

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy

• More than 2 weeks since prior and no concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), St. John's wort, ketoconazole, dexamethasone, the dysrhythmic drugs (e.g., terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice

  • Topical or inhaled steroids allowed
• At least 4 weeks since prior treatment with cytotoxic or biologic agents (6 weeks for mitomycin C or nitrosoureas)
• At least 4 weeks since prior surgery, radiation, hormonal therapy, or other drug therapy
• No concurrent hydroxychloroquine for treatment or prophylaxis of malaria
• No concurrent treatment for rheumatoid arthritis or systemic lupus erythematosus
• No concurrent disease-modifying anti-rheumatic drug (DMARD)
• No other concurrent investigational or commercial agents or therapies with the intent to treat the patient's malignancy