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

This study has been terminated.
(The study was closed because of the number of known toxicities observed despite a treatment-naïve population.)
Sponsor:
Collaborator:
Information provided by:
University of California, Davis
ClinicalTrials.gov Identifier:
NCT00807755
First received: December 11, 2008
Last updated: July 22, 2011
Last verified: July 2011

December 11, 2008
July 22, 2011
January 2009
August 2010   (final data collection date for primary outcome measure)
Safety and feasibility [ Time Frame: April 2011 ] [ Designated as safety issue: Yes ]
Safety and feasibility [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00807755 on ClinicalTrials.gov Archive Site
  • Maximum-tolerated dose as assessed by NCI CTCAE, Version 3.0 [ Time Frame: April 2011 ] [ Designated as safety issue: Yes ]
  • Dose-limiting toxicities and toxicity profile as assessed by NCI CTCAE, Version 3.0 [ Time Frame: April 2011 ] [ Designated as safety issue: Yes ]
  • Efficacy of this regimen in patients with small cell lung cancer [ Time Frame: October 2011 ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters [ Time Frame: June 2011 ] [ Designated as safety issue: No ]
  • Exploratory biomarker analysis [ Time Frame: June 2011 ] [ Designated as safety issue: No ]
  • Maximum-tolerated dose as assessed by NCI CTCAE, Version 3.0 [ Designated as safety issue: Yes ]
  • Dose-limiting toxicities and toxicity profile as assessed by NCI CTCAE, Version 3.0 [ Designated as safety issue: Yes ]
  • Efficacy of this regimen in patients with small cell lung cancer [ Designated as safety issue: No ]
  • Pharmacokinetic parameters [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Everolimus, Carboplatin, and Etoposide in Treating Patients With Small Cell Lung Cancer or Other Advanced Solid Tumors
Phase I Trial of Carboplatin and Etoposide in Combination With Everolimus (RAD001) in Advanced Solid Tumors, With Emphasis on Small Cell Lung Cancer (SCLC)

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.

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.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Lung Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Drug: carboplatin
    IV (in the vein) on Day 1 of each 21-day cycle, as per dose escalation schedule (dose levels 1 and 2: AUC 5; dose levels 3 and 4: AUC 6). Number of cycles: 6 maximum.
    Other Name: Paraplatin
  • Drug: etoposide
    80mg/m2, IV (in the vein) on Days 1, 2, 3 of a 21-day cycle (all dose levels). Number of cycles: 6 maximum.
    Other Name: Eposin, Etopophos, Vepesid, VP-16
  • Drug: everolimus
    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:
    • RAD001
    • Afinitor
  • Other: Correlative studies
    Pharmacokinetics: blood collected Cycle 1, Days 1, 15; Cycle 2, Day 1. Biomarker Analysis: blood collected pre-study and Cycles 2-6, Day 1.
Experimental: Phase I dose-escalation
Interventions:
  • Drug: carboplatin
  • Drug: etoposide
  • Drug: everolimus
  • Other: Correlative studies
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
5
Not Provided
August 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00807755
CDR0000628772, P30CA093373, UCDCC-214, 200816670-1, NOVARTIS-UCDCC-214
Yes
David Gandara, MD, University of California School of Medicine - Davis
University of California, Davis
National Cancer Institute (NCI)
Principal Investigator: David Gandara, MD University of California School of Medicine - Davis
University of California, Davis
July 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP