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

Lung Cancer Clinical Trial

Official title:

Phase I Trial of Carboplatin and Etoposide in Combination With Everolimus (RAD001) in Advanced Solid Tumors, With Emphasis on Small Cell Lung Cancer (SCLC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00807755
• Other study ID #: UCDCC#214
• Secondary ID: 200816670CRAD001
• Status: Terminated
• Phase: Phase 1
• First received: December 11, 2008
• Last updated: January 5, 2018
• Start date: March 2009
• Est. completion date: December 2011

Study information

• Verified date: January 2018
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

Primary

• Determine the safety and feasibility of everolimus combined with carboplatin and etoposide in patients with advanced solid tumors, with emphasis on small cell lung cancer (SCLC).

Secondary

• Determine the maximum-tolerated dose of this regimen in these patients.

• Describe the dose-limiting toxicities and toxicity profile associated with this regimen in these patients.

• Determine, preliminarily, the efficacy of this regimen in an expanded cohort of patients with SCLC.

• Assess the pharmacokinetic parameters of everolimus in this combination.

OUTLINE: This is a dose-escalation study.

Patients receive oral everolimus on days 1-21, carboplatin IV over 15-30 minutes on day 1, and etoposide IV over 30 minutes on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients in the expanded cohort undergo blood collection on days 1, 15, and 22 for pharmacokinetic studies by liquid chromatography-tandem mass spectrometry.

After completion of study therapy, patients are followed for 30 days.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: December 2011
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• Carboplatin
Intravenous (IV) on Day 1 of each 21-day cycle, as per dose escalation schedule (dose levels 1 and 2: dose levels 3 and 4). Number of cycles: 6 maximum.
• Etoposide
80mg/m2, Intravenous on Days 1, 2, 3 of a 21-day cycle (all dose levels). Number of cycles: 6 maximum.
• RAD001
Orally on Days 1-21 of a 21-day cycle, as per dose escalation schedule (dose level 1: 2.5 mg, dose level 2: 5 mg, dose level 3: 5.0 mg, and dose level 4: 10.0 mg). Number of cycles: unlimited (drug taken from Day 1 until progression of disease or unacceptable toxicity).

Locations

Country	Name	City	State
United States	University of California Davis Cancer Center	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Davis	Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and feasibility of combining RAD001 with carboplatin and etoposide in advanced solid tumors, with emphasis on SCLC.		Up to 1 year from start of treatment
Secondary	Maximum-tolerated dose as assessed by NCI CTCAE, Version 3.0		April 2011
Secondary	Dose-limiting toxicities and toxicity profile as assessed by NCI CTCAE, Version 3.0		Up to one year.
Secondary	Preliminary efficacy of this regimen in patients with small cell lung cancer		Up to one year
Secondary	Pharmacokinetic parameters		Up to one year
Secondary	Exploratory biomarker analysis		Up to one year