Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00276575
Bevacizumab, Everolimus, and Erlotinib in Treating Patients With Advanced Solid Tumors
A Phase 1 study testing bevacizumab, erlotinib hydrochloride and everolimus in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Herbert Hurwitz, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- bevacizumab, erlotinib hydrochloride and everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2005to Sep 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
About this study
Official title: Phase I Study of Bevacizumab in Combination With Everolimus and Erlotinib in Advanced Cancer
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.
Read the 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.
- Being tested
- bevacizumab, erlotinib hydrochloride, everolimus
- Keywords
- unspecified adult solid tumor, protocol specific
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabBiological
erlotinib hydrochlorideDrug
everolimusDrug
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: bevacizumab; Drug: erlotinib hydrochloride; Drug: everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
Its primary objective is to estimate the MTD/recommended phase II dose combination or regimen
Measured: Until study completion
Secondary outcomes (1)
Safety
endpoints will be evaluated in an exploratory fashion
Measured: Until study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2006 (estimated)
- Study startMar 2005
- Primary completionOct 2012
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herbert Hurwitz, MD
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Herbert Hurwitz, MD, Duke University
- Investigators
- Herbert I. Hurwitz, MD, Principal investigator, Duke Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00276575
- Sponsor's protocol ID
- Pro00008048
- Other IDs
- DUMC-6026-05-6R1, GENENTECH-DUMC-6026-05-6R1, NOVARTIS-DUMC-6026-05-6R1, CDR0000449970
- Status last verified
- Nov 2014
- First submitted
- 12 Jan 2006
- Last updated
- 19 Nov 2014
- Results posted
- No
Publications
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.
PubMed 21079958
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Bevacizumab in Combination With Everolimus and Erlotinib in Advanced Cancer
- ClinicalTrials.gov ID
- NCT00276575
- Acronym / sponsor ID
- Pro00008048
- Keywords
- unspecified adult solid tumor, protocol specific
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Herbert Hurwitz, MDUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2005
- Primary completion
- Oct 2012 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 13 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab, Everolimus, and Erlotinib | Experimental | Biological: bevacizumab, Drug: erlotinib hydrochloride, Drug: everolimusDose 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bevacizumab | Biological | Bevacizumab, Everolimus, and Erlotinib |
| erlotinib hydrochloride | Drug | Bevacizumab, Everolimus, and Erlotinib |
| everolimus | Drug | Bevacizumab, Everolimus, and Erlotinib |
Primary outcome
Maximum Tolerated Dose
Time frame: Until study completion
Its primary objective is to estimate the MTD/recommended phase II dose combination or regimen
1 secondary outcome
Safety
Time frame: Until study completion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2014.
- Results publication: PubMed 21079958Bullock 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Herbert I. Hurwitz, MD principal investigator
Duke Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bevacizumab, erlotinib hydrochloride and everolimus in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Herbert Hurwitz, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: Until study completion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00276575, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2014.