Erlotinib and Everolimus in Treating Patients With Metastatic Breast Cancer

NCT00574366 | Completed Phase 1 DMC

• 2 other identifiers: VICC BRE 0523VU-VICC-BRE-0523
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Erlotinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib together with everolimus may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of giving erlotinib together with everolimus and to see how well it works in treating patients with metastatic breast cancer.

Conditions

Breast Cancer

Keywords

recurrent breast cancer; stage IV breast cancer; male breast cancer

Outcome Measures

Primary Outcomes (2)

• To determine the maximum tolerated dose (MTD) of RAD001 given in combination with erlotinib (Phase I)

  MTD will be the dose level at which fewer than 2 of 6 (or 33% of) patients experience dose limiting toxicity (DLT), starting at first 4 weeks.

  at 4 weeks

• Anti-tumor activity of RAD001 in combination with erlotinib (Phase II)

  Clinical benefit based upon number of patients with complete response (CR), partial response (PR), and stable disease (SD). Responses are determined by Response Evaluation in Solid Tumors (RECIST)criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) \> 30% decrease in the sum of the longest diameter (LD) of target lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions

  at 6 months

Secondary Outcomes (1)

• Time to progression (Phase II)

  from study entry to disease progression

Other Outcomes (1)

• To determine PTEN, pAkt, pP70S6K1 and pEGFR in primary tumors at baseline.

  at day one

Study Arms (1)

Erlotinib/RAD001 Ph I

EXPERIMENTAL

Tarceva (OSI-774; erlotinib) Everolimus (RAD001) Study did not progress to Phase II: Experimental: Erlotinib/RAD001 Phase II Maximum tolerated dose of erlotinib (Tarceva,OSI-774) and RAD001 (Everolimus)

Drug: erlotinib; Drug: RAD001

Interventions

erlotinib DRUG

Levels: * 1 Erlotinib 50 mg/d * 2 Erlotinib 50 mg/d * 1 Erlotinib 100 mg/d * 2 Erlotinib 100 mg/d * 3 Erlotinib 150 mg/d * 4 Erlotinib 150 mg/d

Also known as: Tarceva (OSI-774)

Erlotinib/RAD001 Ph I

RAD001 DRUG

Levels minus 1: RAD001 2.5 mg/d minus 2: RAD001 2.5 every other day 1. RAD001 2.5 mg per day 2. RAD001 5 mg per day 3. RAD001 10 mg per day 4. RAD001 10 mg per day

Also known as: everolimus

Erlotinib/RAD001 Ph I

Eligibility Criteria

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

You may qualify if:

• Menopausal status not specified
• ECOG performance status 0-1
• Absolute neutrophil count ≥ 1,500/mm\^3
• Platelet count ≥ 100,000/mm\^3
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT and SGPT ≤ 2.5 times ULN
• Albumin \> 30 g/L
• Creatinine ≤ 1.5 upper limit of normal
• INR normal provided the patient is not on warfarin therapy
• Not pregnant or nursing
• Negative pregnancy test for premenopausal patients
• Fertile patients must use effective barrier method contraception during and for 3 months after completion of study treatment
• Patients must be disease-free of prior invasive cancers for \> 5 years with the exception of basal cell or squamous cell cancer of the skin or cervical carcinoma in situ

You may not qualify if:

• Serious or non-healing active wound, ulcer, or bone fracture
• Known human immunodeficiency virus positivity
• Uncontrolled intercurrent illness including, but not limited to, any of the following
• Ongoing or active infection requiring parenteral antibiotics
• Impairment of lung function (COPD, lung conditions requiring oxygen therapy)
• Symptomatic congestive heart failure (New York Heart Association class III or IV heart disease)
• Unstable angina pectoris or myocardial infarction within the past 6 months
• Uncontrolled hypertension (i.e., systolic blood pressure \> 180 mm Hg or diastolic blood pressure \> 100 mm Hg, found on two consecutive measurements separated by a 1-week period despite adequate medical support)
• Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment)
• Uncontrolled diabetes
• Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary
• PRIOR CONCURRENT THERAPY:
• See Disease Characteristics
• Prior trastuzumab (Herceptin®) in the first-line treatment of metastatic breast cancer is required for patients who have HER2/neu overexpressing tumors
• More than 6 months since prior cardiac angioplasty or stenting

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, 37064, United States

Location

Vanderbilt-Ingram Cancer Center at Franklin

Nashville, Tennessee, 37064, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Erlotinib Hydrochloride; Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Ingrid Mayer, MD

  Vanderbilt-Ingram Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist

Study Record Dates

• First Submitted: December 14, 2007
• First Posted: December 17, 2007
• Study Start: December 1, 2005
• Primary Completion: January 1, 2009
• Study Completion: February 1, 2009
• Last Updated: May 10, 2016

Record last verified: 2016-05

Locations

US (3)