A Phase I Trial of Hydroxychloroquine in Combination With Temsirolimus in Patients With Refractory Solid Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed refractory solid tumor for which no curative standard
therapy exists

- Metastatic disease

- Treated brain metastases that have been stable ≥ 3 months allowed

- At least 1 week since prior steroids

PATIENT CHARACTERISTICS:

- ECOG performance status of 0-1

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Creatinine ≤ 2 times upper limit of normal (ULN)

- ALT and AST ≤ 5 times ULN

- Total bilirubin ≤ 1.5 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No serious concurrent infection or medical illness that would jeopardize the ability
of the patient to receive the treatment outlined in this protocol with reasonable
safety

- No prior or other concurrent malignancy except for curatively treated
carcinoma-in-situ at any site or basal cell carcinoma or squamous cell carcinoma of
the skin

- Patients who have been free of disease (any prior malignancy) for ≥ 5 years are
eligible

- No porphyria

- No psoriasis, except well controlled psoriasis under the care of a specialist

- No previously documented macular degeneration or diabetic retinopathy

- No HIV positivity

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Any number and type of prior anticancer therapies allowed

- No prior mTOR inhibitors

- At least 4 weeks since prior immunotherapy (i.e., aldesleukin, interferon, CTLA-4) or
chemotherapy and recovered

- At least 2 weeks since prior oral targeted therapy and recovered

- At least 4 weeks since prior and no other concurrent investigational anticancer
therapy (except for vaccines)

- No other concurrent therapy

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent cytochrome P450 enzyme-inducing anticonvulsant drugs (i.e., phenytoin,
carbamazepine, phenobarbital, primidone, or oxcarbazepine)

- Concurrent non-enzyme inducing anticonvulsants, including felbamate, valproic acid,
gabapentin, lamotrigine, tiagabine, topiramate, zonisamide, or levetiracetam allowed

- Concurrent hematologic growth factors (filgrastim [G-CSF], pegfilgrastim, epoetin
alfa) allowed in patients with severe myelosuppression