Everolimus, Carboplatin, and Etoposide in Treating Patients With Small Cell Lung Cancer or Other Advanced Solid Tumors

• Status: Terminated
• Trial end date: 2011-12-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Everolimus 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. Drugs used in chemotherapy, such as carboplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with everolimus may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus, carboplatin, and etoposide in treating patients with small cell lung cancer or other advanced solid tumors.

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

Details

• Lead Sponsor: University of California, Davis
• Collaborator: Novartis
• Treatments: Carboplatin; Etoposide; Etoposide phosphate; Everolimus; Sirolimus

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced solid tumors for which curative standard treatments are not available

• Ten additional patients with extensive stage small cell lung cancer are accrued to the expanded cohort once a maximum tolerate dose (or a dose for further exploration) is determined

• Must be chemotherapy naive

• Measurable or evaluable disease

• Prior irradiated disease sites are considered measurable if there is clear disease progression following radiation therapy

• No uncontrolled brain or leptomeningeal metastases (including those requiring glucocorticoids)

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2

• Life expectancy > 3 months

• Granulocyte count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Creatinine ≤ 1.3 mg/dL OR creatinine clearance > 40 mL/min

• Serum bilirubin ≤ 1.5 mg/dL (regardless of liver involvement)

• SGOT ≤ 3 times upper limit of normal (ULN)

• INR ≤ 1.3 (≤ 3 if on anticoagulation)

• Fasting serum cholesterol ≤ 300 mg/dL*

• Fasting triglycerides ≤ 2.5 times ULN*

• No severe and/or uncontrolled medical co-morbidities or other conditions that could affect participation in the study including, but not limited to, the following:

• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to first study treatment

• Serious uncontrolled cardiac arrhythmia

• Severely impaired lung function

• Active (acute or chronic) or uncontrolled infection

• Non-malignant medical illness that is uncontrolled or that the control may be jeopardized by the study therapy

• Liver disease (i.e., cirrhosis, chronic active hepatitis, chronic persistent hepatitis)

• No uncontrolled diabetes mellitus (i.e., fasting serum glucose > 1.5 times ULN)

• No HIV seropositivity

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No oral, implantable, or injectable contraceptives

• 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 hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients

• Must be able to take and retain oral medication

• No peripheral neuropathy > grade 1 as per NCI CTCAE vs. 3 NOTE: *In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid-lowering medication.

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from prior therapy

• More than 3 weeks since prior and no concurrent investigational drugs

• At least 3 weeks since prior chemotherapy

• At least 2 weeks since prior major surgery or completion of radiotherapy

• No immunization with attenuated live vaccines within the past week or during study therapy

• No prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, or everolimus)

• No chronic treatment with systemic steroids or other immunosuppressive agents

• No concurrent oral anti-vitamin K medication (except low dose coumadin)

• No concurrent medications interfering with everolimus

• No other concurrent anticancer agents