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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00807755
Recruitment Status : Terminated (Number of known toxicities observed despite a treatment-naïve population)
First Posted : December 12, 2008
Last Update Posted : January 9, 2018
Information provided by (Responsible Party):
University of California, Davis

Brief 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.

Condition or disease Intervention/treatment Phase
Lung Cancer Unspecified Adult Solid Tumor, Protocol Specific Drug: Carboplatin Drug: Etoposide Drug: RAD001 Phase 1

Detailed Description:



  • 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).


  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 2009
Actual Primary Completion Date : August 2010
Actual Study Completion Date : December 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Phase I Dose-Escalation
This is a phase I dose escalation study of RAD001 and carboplatin/etoposide. Patients will be accrued in a standard 3 + 3 design based on toxicities experienced during the first cycle. Ten additional chemotherapy naive extensive stage small cell lung cancer (ES-SCLC) patients will be accrued at the Maximum Tolerated Dose (MTD) for further toxicity and response assessment.
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.
Other Name: Paraplatin
Drug: Etoposide
80mg/m2, Intravenous on Days 1, 2, 3 of a 21-day cycle (all dose levels). Number of cycles: 6 maximum.
Other Names:
  • Eposin
  • Etopophos
  • Vepesid
  • VP-16
Drug: 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).
Other Names:
  • Everolimus
  • Afinitor

Primary Outcome Measures :
  1. Safety and feasibility of combining RAD001 with carboplatin and etoposide in advanced solid tumors, with emphasis on SCLC. [ Time Frame: Up to 1 year from start of treatment ]

Secondary Outcome Measures :
  1. Maximum-tolerated dose as assessed by NCI CTCAE, Version 3.0 [ Time Frame: April 2011 ]
  2. Dose-limiting toxicities and toxicity profile as assessed by NCI CTCAE, Version 3.0 [ Time Frame: Up to one year. ]
  3. Preliminary efficacy of this regimen in patients with small cell lung cancer [ Time Frame: Up to one year ]
  4. Pharmacokinetic parameters [ Time Frame: Up to one year ]
  5. Exploratory biomarker analysis [ Time Frame: Up to one year ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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)


  • 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.


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00807755

United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Principal Investigator: David Gandara, MD University of California School of Medicine - Davis

Responsible Party: University of California, Davis Identifier: NCT00807755     History of Changes
Other Study ID Numbers: UCDCC#214
200816670 ( Other Identifier: UC Davis )
CRAD001CUS41T ( Other Identifier: Novartis Pharmaceuticals )
UCDCC-214 ( Other Identifier: University of California, Davis - Cancer Center )
First Posted: December 12, 2008    Key Record Dates
Last Update Posted: January 9, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of California, Davis:
unspecified adult solid tumor, protocol specific
extensive stage small cell lung cancer
recurrent small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide phosphate
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action