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

Phase 1

Completed

• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Interventions: Biological: bevacizumab; Drug: erlotinib hydrochloride; Drug: everolimus

• Registration Number: NCT00276575
• Lead Sponsor: Herbert Hurwitz, MD

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.

Detailed Description

OBJECTIVES:

Primary

* Estimate the maximum tolerated dose (MTD)/recommended phase II regimen of everolimus and erlotinib hydrochloride when given with bevacizumab in patients with advanced solid tumors.

* Evaluate safety of bevacizumab, everolimus, and erlotinib hydrochloride in these patients.

Secondary

* Describe the impact of this combination therapy on dermal wound angiogenesis and inhibition of vascular endothelial growth factor receptor 1 (VEGFR1), mTOR/p70S6K, and other related markers in granulation tissue.

* Evaluate clinical activity (partial response, complete response, or stable disease \> 6 months) associated with this regimen.

OUTLINE: This is a dose-escalation study followed by a randomized study.

* Part 1: Patients receive bevacizumab IV on days 1 and 15 and oral everolimus and oral erlotinib hydrochloride\* once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of patients receive escalating doses of everolimus or escalating doses of everolimus and erlotinib hydrochloride\* until the maximum tolerated dose (MTD) is determined. Patients in part 2 of the study are treated at the MTD of everolimus and erlotinib hydrochloride.

NOTE: \*The first cohort of patients receive bevacizumab and everolimus only until the MTD is determined, the subsequent cohorts of patients receive bevacizumab, everolimus, and erlotinib hydrochloride

* Part 2: Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral everolimus once daily beginning on day 1, oral erlotinib hydrochloride once daily beginning on day 15, and bevacizumab IV once every 2 weeks beginning on day 15. Treatment continues in the absence of disease progression or unacceptable toxicity.

* Arm II: Patients receive oral erlotinib hydrochloride once daily beginning on day 1, oral everolimus once daily beginning on day 15, and bevacizumab IV once every 2 weeks beginning on day 15. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Study Timeline

• Study Start: 2005-03
• Study First Submitted: 2006-01-12
• Study First Submitted QC: 2006-01-12
• Study First Posted: 2006-01-13
• Primary Completion: 2012-10
• Study Completion: 2014-09
• Status Verified: 2014-11
• Last Update Submitted: 2014-11-18
• Last Update Posted: 2014-11-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bevacizumab, Everolimus, and Erlotinib	bevacizumab	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
Bevacizumab, Everolimus, and Erlotinib	erlotinib hydrochloride	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
Bevacizumab, Everolimus, and Erlotinib	everolimus	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

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose	Until study completion	Its primary objective is to estimate the MTD/recommended phase II dose combination or regimen

Secondary Outcome Measures

Name	Time	Method
Safety	Until study completion	endpoints will be evaluated in an exploratory fashion

Trial Locations

Locations (1)

Duke Comprehensive Cancer Center; 🇺🇸 Durham, North Carolina, United States