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
  Purpose

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 Intervention Phase
Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: carboplatin
Drug: etoposide
Drug: everolimus
Other: Correlative studies
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Safety and feasibility [ Time Frame: April 2011 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 5
Study Start Date: January 2009
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I dose-escalation 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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00807755

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

No publications provided

Responsible Party: David Gandara, MD, University of California School of Medicine - Davis
ClinicalTrials.gov Identifier: NCT00807755     History of Changes
Other Study ID Numbers: CDR0000628772, P30CA093373, UCDCC-214, 200816670-1, NOVARTIS-UCDCC-214
Study First Received: December 11, 2008
Last Updated: July 22, 2011
Health Authority: United States: Food and Drug Administration

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
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide
Etoposide phosphate
Sirolimus
Carboplatin
Everolimus
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 17, 2014