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

Phase 1
18 Years
Not Enrolling
Lung Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

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



- 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.

Inclusion Criteria


- 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


- 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

- 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

- 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

- No prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, or

- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and feasibility

Outcome Time Frame:

April 2011

Safety Issue:


Principal Investigator

David Gandara, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California School of Medicine - Davis


United States: Food and Drug Administration

Study ID:




Start Date:

January 2009

Completion Date:

Related Keywords:

  • Lung Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • extensive stage small cell lung cancer
  • recurrent small cell lung cancer
  • Lung Neoplasms
  • Small Cell Lung Carcinoma
  • Neoplasms



University of California Davis Cancer CenterSacramento, California  95817