Bevacizumab, Everolimus, and Erlotinib in Treating Patients With Advanced Solid Tumors

NCT00276575 | Completed Phase 1

• 5 other identifiers: Pro00008048DUMC-6026-05-6R1GENENTECH-DUMC-6026-05-6R1NOVARTIS-DUMC-6026-05-6R1CDR0000449970
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and everolimus may also block blood flow to the tumor. Giving everolimus and erlotinib together with bevacizumab may kill more tumor cells. PURPOSE: This randomized phase I trial is studying the side effects and best dose of erlotinib and everolimus when given together with bevacizumab in treating patients with advanced solid tumors.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Its primary objective is to estimate the MTD/recommended phase II dose combination or regimen

  Until study completion

Secondary Outcomes (1)

• Safety

  Until study completion

Study Arms (1)

Bevacizumab, Everolimus, and Erlotinib

EXPERIMENTAL

Dose Level Dose Bevacizumab (mg/kg q2wks) Everolimus (mg daily) Erlotinib (mg daily) -1 5 5 --- 1. 10 5 --- 2. 10 10 --- 3. 10\* 10\* 75 4. 10\* 10\* 150

Biological: bevacizumab; Drug: erlotinib hydrochloride; Drug: everolimus

Interventions

bevacizumab BIOLOGICAL

Bevacizumab, Everolimus, and Erlotinib

erlotinib hydrochloride DRUG

Bevacizumab, Everolimus, and Erlotinib

everolimus DRUG

Bevacizumab, Everolimus, and Erlotinib

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed malignancy * Metastatic or unresectable disease * Standard curative or palliative measures do not exist OR are no longer effective * No CNS metastases * No centrally-located non-small cell lung cancer PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Leukocytes ≥ 3,000/mm³ * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST/ALT ≤ 2.5 times ULN (5 times ULN if known hepatic metastases) * Urine protein to creatinine ratio ≤ 1.0 OR urine protein \< 1 g by 24 hour urine collection * Creatinine clearance ≥ 50 mL/min OR creatinine normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during study and for up to 4 months after study treatment has stopped * No uncontrolled hypertriglyceridemia (i.e., fasting serum triglyceride \> 350 mg/dL) * No uncontrolled hypercholesterolemia (i.e., fasting serum cholesterol \> 300 mg/dL) * No poorly controlled hypertension (i.e., blood pressure \> 160/100 mm Hg) * No poorly controlled or clinically significant atherosclerotic vascular disease * No thrombosis within 6 months * No venous thromboembolic event within 6 months * No arterial thromboembolic events within 12 months * No cerebrovascular accident or transient ischemic attack in past 12 months * No myocardial infarction or unstable angina in past 12 months * No clinically significant peripheral vascular disease in past 12 months * No New York Heart Association class II-IV congestive heart failure * Atrial or supraventricular tachycardias well controlled with beta blocker or calcium channel blocker allowed * Chronic pacemaker use allowed * No serious cardiac arrhythmia requiring medication * No other clinically significant cardiovascular disease * No hemoptysis \> 1 tablespoon within 6 months * No presence of bleeding diathesis * No coagulopathy * No presence of significant gastrointestinal (GI) disorders that would affect drug absorption * No hemodynamically significant GI bleeding * No history of intolerance to bevacizumab, everolimus, or erlotinib * No other major bleeding event * No ongoing or active infection * No psychiatric illness or social situations that would limit safety or compliance with study requirements * No other uncontrolled intercurrent illness PRIOR CONCURRENT THERAPY: * No angioplasty or cardiac or vascular stenting within the past 12 months * No major surgery within past 28 days * No other investigational agents within past 28 days * No chemotherapy for cancer within past 21 days * No biologic therapy for cancer within past 21 days * No radiation therapy for cancer within past 21 days * No hormonal therapy for cancer within past 21 days * No minor surgical procedures within past 14 days * No concurrent antiplatelet agents other than aspirin \< 325 mg/day * No use of statin drugs other than pravastatin or atorvastatin * Initiation of blood pressure (BP) medication is permitted prior to study entry provided that BP \< 150/90 mm Hg on 3 measurements over one week (study day -7 to 1) before starting treatment * No concurrent grapefruit juice * No concurrent therapeutic anticoagulation * Prophylactic low-dose anticoagulation for indwelling catheters is permitted * No concurrent administration of any of the following drugs: * Nicardipine * Verapamil * Clotrimazole * Fluconazole * Itraconazole * Ketoconazole * Clarithromycin * Erythromycin * Troleandomycin * Cisapride * Metoclopramide * Bromocriptine * Cimetidine * Danazol * HIV-protease inhibitors (e.g., ritonavir, indinavir) * Hypericum perforatum (St. John's wort) * Carbamazepine * Phenobarbital * Phenytoin * Diltiazem * Rifabutin * Rifapentine * Rifampin

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

Sponsors & Collaborators

• Herbert Hurwitz, MD: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Bullock KE, Petros WP, Younis I, Uronis HE, Morse MA, Blobe GC, Zafar SY, Gockerman JP, Lager JJ, Truax R, Meadows KL, Howard LA, O'Neill MM, Broadwater G, Hurwitz HI, Bendell JC. A phase I study of bevacizumab (B) in combination with everolimus (E) and erlotinib (E) in advanced cancer (BEE). Cancer Chemother Pharmacol. 2011 Feb;67(2):465-74. doi: 10.1007/s00280-010-1507-6. Epub 2010 Nov 16.

  PMID: 21079958 RESULT

MeSH Terms

Interventions

Bevacizumab; Erlotinib Hydrochloride; Everolimus

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Herbert I. Hurwitz, MD

  Duke Cancer Institute

  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 INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 12, 2006
• First Posted: January 13, 2006
• Study Start: March 1, 2005
• Primary Completion: October 1, 2012
• Study Completion: September 1, 2014
• Last Updated: November 19, 2014

Record last verified: 2014-11

Locations

US (1)