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

NCT00807755 | Terminated Phase 1 DMC FDA Drug

• 4 other identifiers: UCDCC#214200816670CRAD001CUS41TUCDCC-214
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific; extensive stage small cell lung cancer; recurrent small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Maximum-tolerated dose as assessed by NCI CTCAE, Version 3.0

  April 2011

• Dose-limiting toxicities and toxicity profile as assessed by NCI CTCAE, Version 3.0

  Up to one year.

• Preliminary efficacy of this regimen in patients with small cell lung cancer

  Up to one year

• Pharmacokinetic parameters

  Up to one year

• Exploratory biomarker analysis

  Up to one year

Study Arms (1)

Phase I Dose-Escalation

EXPERIMENTAL

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; Drug: Etoposide; Drug: RAD001

Interventions

Carboplatin DRUG

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.

Also known as: Paraplatin

Phase I Dose-Escalation

Etoposide DRUG

80mg/m2, Intravenous on Days 1, 2, 3 of a 21-day cycle (all dose levels). Number of cycles: 6 maximum.

Also known as: Eposin, Etopophos, Vepesid, VP-16

Phase I Dose-Escalation

RAD001 DRUG

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).

Also known as: Everolimus, Afinitor

Phase I Dose-Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, Davis: lead
• Novartis: collaborator

Study Sites (1)

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Small Cell Lung Carcinoma

Interventions

Carboplatin; Etoposide; etoposide phosphate; Everolimus

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Sirolimus; Macrolides; Lactones

Study Officials

• David Gandara, MD

  University of California School of Medicine - Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2008
• First Posted: December 12, 2008
• Study Start: March 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: December 1, 2011
• Last Updated: January 9, 2018

Record last verified: 2018-01

Locations

US (1)