Cisplatin and Everolimus in Treating Patients With Advanced Solid Tumors

• Status: Completed
• Trial end date: 2011-09-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Everolimus may also help cisplatin work better by making tumor cells more sensitive to the drug. Giving cisplatin together with everolimus may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with cisplatin in treating patients with advanced solid tumors or recurrent or metastatic solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cisplatin; Everolimus; Sirolimus

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:

• Advanced solid tumor (part A)

• Confirmation by core biopsy or fine-needle aspiration allowed

• Solid tumor (part B)

• Recurrent or metastatic disease

• Easily accessible for biopsy

• Measurable disease

• No uncontrolled brain or leptomeningeal metastases

• No requirement for glucocorticoids

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%

• Absolute neutrophil count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin > 10 g/dL

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST and ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases are present)

• Creatinine normal OR creatinine clearance ≥ 55 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy

• No HIV positivity

• No peripheral neuropathy ≥ grade 2

• No hypertriglyceridemia ≥ grade 2

• No impaired gastrointestinal function or gastrointestinal disease that may alter the absorption of everolimus, including any of the following:

• Ulcerative disease

• Uncontrolled nausea

• Vomiting

• Diarrhea

• Malabsorption syndrome

• Small bowel resection

• No other concurrent severe and/or uncontrolled medical disease that would compromise study participation, including any of the following:

• Uncontrolled diabetes

• Unstable angina

• New York Heart Association class III or IV congestive heart failure

PRIOR CONCURRENT THERAPY:

• No more than 3 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease

• At least 4 weeks since prior major surgery and recovered

• At least 4 weeks since prior radiation therapy and recovered

• At least 4 weeks since prior systemic anticancer therapy and recovered

• At least 4 weeks since prior and no other concurrent investigational drugs

• No prior everolimus or other agents specifically targeting mTOR

• No prior radiation therapy to > 25% of the bone marrow

• No prior radiation therapy to the whole pelvis and/or brain

• No concurrent chronic steroid treatment (> 5 mg/day of prednisone)

• Concurrent low-dose steroid replacement regimens (≤ 5 mg/day of prednisone) allowed

• No concurrent immunosuppressive agents

• No other concurrent anticancer agents

• No concurrent agents known to be strong inhibitors or inducers of isoenzyme CYP3A