Colorectal AdenocarcinomaPhase 2BEV/EVNCT00597506
Expanded Cohort for Metastatic Colorectal Cancer (MCRC) Using Bevacizumab + Everolimus
A Phase 2 study testing Bevacizumab and Everolimus in people with Colorectal Adenocarcinoma, run by Herbert Hurwitz at 1 site in United States.
Trial summary
The purpose of this study is to find the safest and most effective dose of the drugs bevacizumab and everolimus given in combination for the treatment of metastatic colorectal cancer. Bevacizumab (also called Avastin™) is a drug that is given intravenously (through a vein). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Adenocarcinoma
- What is being tested?
- Bevacizumab and Everolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2007to Jun 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- Patients must have histologically confirmed adenocarcinoma of the colon or rectum that has progressed on, or patient could not tolerate, fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab and/or panitumumab chemotherapy. Disease must be measurable or evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- Patients must not have had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to study day 1. Patients must not have had major surgery within the 28 days prior to study day 1 or minor surgical procedures within the 7 days prior to study day 1.
- Age >18 years.
- Karnofsky performance status > 70 percent
- Life expectancy of at least 3 months.
- Patients must have normal organ and marrow function as defined in the protocol
- The effect of the investigational drugs on the developing human fetus is not known, but these drugs are likely to be embryo- and feto- toxic. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician and study PI immediately. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Patients who are pregnant and/or lactating are excluded from this study.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within the 28 days prior to day 1 of the study.
- Patients who have received any other investigational agents within the 28 days prior to day 1 of the study.
- Patients with known central nervous system (CNS) metastases.
- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg). Initiation of antihypertensive is permitted provided adequate control is documented over at least 1 week before starting treatment.
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
- Symptomatic peripheral vascular disease
Show all 26Show fewer
- Evidence of bleeding diathesis or coagulopathy. Patients on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least 2 weeks.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment (56 days for hepatectomy, open thoracotomy, major neurosurgery) or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure excluding study-related procedures or placement of a vascular access device, within 7 days prior to expected start of treatment.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
- Serious, non-healing wound, ulcer, or bone fracture
- Proteinuria at screening as demonstrated by either Urine protein:creatinine (UPC) ratio greater than or equal to 1.0 at screening
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix G)
- History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study enrollment
- History of stroke or transient ischemic attack within 6 months prior to study enrollment
- History of intolerance or hypersensitivity to prior treatment with bevacizumab or RAD001.
- Chronic treatment with systemic steroids or another immunosuppressive agent, though steroids may be used on an as-needed basis - ie - for treatment of nausea. Treatment with megace or low dose glucocorticoids is permitted for treatment of anorexia.
- Other concurrent severe and/or uncontrolled medical disease which could compromise safety of treatment as so judged by treating physician
- A known history of HIV seropositivity, hepatitis C virus, acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment.
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or significant small bowel resection)
- Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except coumadin). No history of active GI bleeding or other major bleeding within previous 6 months.
- Patients unwilling to or unable to comply with the protocol
- Medical need for the continuous administration of any drugs which affect Cytochrome P450, family 3, subfamily A (CYP3A), though the use of low dose glucocorticoids for anorexia and /or nausea is permitted.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety or compliance with study requirements or may interfere with the interpretation of the results.
- History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Expanded Cohort of Patients With Refractory Metastatic Colorectal Cancer (MCRC) Treated With Bevacizumab and Everolimus
The purpose of this study is to find the safest and most effective dose of the drugs bevacizumab and everolimus given in combination for the treatment of metastatic colorectal cancer. Bevacizumab (also called Avastin™) is a drug that is given intravenously (through a vein). Everolimus (also called RAD001) is a tablet that is taken by mouth.
Bevacizumab is a protein that is thought to prevent the formation of blood vessels tumors need to grow. RAD001 has multiple capabilities, like bevacizumab it may prevent the formation of blood vessels needed by tumors and it also may stop tumor growth.
This study will try to find the safest dose of these drugs that can be tolerated when taken in combination. The study will look at how the drugs work in the body, and will see if there is any effect on metastatic colorectal cancer.
Read the detailed description
This open-label, non-randomized expanded cohort trial of bevacizumab and RAD001 for patients with refractory metastatic colorectal cancer is designed to assess preliminary efficacy as well as the safety and tolerability of this combination. Patients will be accrued to this study at Duke University Medical Center and The Duke Oncology Outreach Network (DON)
After satisfying eligibility and screening criteria, patients will be treated on 28 day cycles.
- The treatment regimen is as follows: 10 mg/kg Bevacizumab intravenous on days 1 and 15 and 10mg everolimus (RAD001) daily by mouth
- Toxicity will be assessed every visit, and as clinically indicated.
- Efficacy will be assessed every 2 cycles, and as clinically indicated.
- Patients may remain on treatment as long as they are deemed to be clinically benefiting from treatment, do not have progressive disease on restaging imaging (Section 6.0), or do not have any other reason for discontinuation of treatment as outlined in Section 3.4.
- Patients will undergo correlative studies as outlined in the study protocol
- Conditions
- Colorectal Adenocarcinoma
- Being tested
- Bevacizumab, Everolimus
- Keywords
- colorectal, refractory, adenocarcinoma, bevacizumab, everolimus
- Medical subject headings
- Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
10 mg/kg intravenous bevacizumab given days 1 and 15 of each cycle
EverolimusDrug
Also called RAD001
10 mg Everolimus(RAD001) daily by mouth, days 1-28
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab and Everolimus | Experimental | 10 mg Everolimus(RAD001) daily by mouth, days 1-28 10 mg/kg intravenous bevacizumab given days 1 and 15 of each cycle Receives: Drug: Bevacizumab; Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response
Overall response is composed of complete responses and partial responses. Complete response (CR): disappearance of all target lesions; Partial response: at least a 30 percent decrease in the sum of the longest diameter of the target lesions taking as reference the baseline sum longest diameter. Response is assessed at each subject's restaging, approximately ever 2 months.
Measured: Measured 1 month after the last treated subject came off treatment
Progression Free Survival (PFS)
8 week PFS
Measured: interval between start of treatment and 8-week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2008 (estimated)
- Study startOct 2007
- Primary completionJun 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal AdenocarcinomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herbert Hurwitz
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals, Genentech, Inc.
- Responsible party
- Sponsor-investigator, Herbert Hurwitz, Duke University
- Investigators
- Herbert I Hurwitz, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00597506
- Sponsor's protocol ID
- Pro00001574
- Acronym
- BEV/EV
- Status last verified
- Dec 2012
- First submitted
- 26 Dec 2007
- Last updated
- 27 Dec 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Expanded Cohort of Patients With Refractory Metastatic Colorectal Cancer (MCRC) Treated With Bevacizumab and Everolimus
- ClinicalTrials.gov ID
- NCT00597506
- Acronym / sponsor ID
- BEV/EV / Pro00001574
- Conditions
- Colorectal Adenocarcinoma
- Keywords
- colorectal, refractory, adenocarcinoma, bevacizumab, everolimus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Herbert HurwitzUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals, Genentech, Inc.
- Study start
- Oct 2007
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 18 Jan 2008 (estimated)
- Results
- Posted 16 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find the safest and most effective dose of the drugs bevacizumab and everolimus given in combination for the treatment of metastatic colorectal cancer. Bevacizumab (also called Avastin™) is a drug that is given intravenously (through a vein). Everolimus (also called RAD001) is a tablet that is taken by mouth.
Bevacizumab is a protein that is thought to prevent the formation of blood vessels tumors need to grow. RAD001 has multiple capabilities, like bevacizumab it may prevent the formation of blood vessels needed by tumors and it also may stop tumor growth.
This study will try to find the safest dose of these drugs that can be tolerated when taken in combination. The study will look at how the drugs work in the body, and will see if there is any effect on metastatic colorectal cancer.
Detailed description
This open-label, non-randomized expanded cohort trial of bevacizumab and RAD001 for patients with refractory metastatic colorectal cancer is designed to assess preliminary efficacy as well as the safety and tolerability of this combination. Patients will be accrued to this study at Duke University Medical Center and The Duke Oncology Outreach Network (DON)
After satisfying eligibility and screening criteria, patients will be treated on 28 day cycles.
- The treatment regimen is as follows: 10 mg/kg Bevacizumab intravenous on days 1 and 15 and 10mg everolimus (RAD001) daily by mouth
- Toxicity will be assessed every visit, and as clinically indicated.
- Efficacy will be assessed every 2 cycles, and as clinically indicated.
- Patients may remain on treatment as long as they are deemed to be clinically benefiting from treatment, do not have progressive disease on restaging imaging (Section 6.0), or do not have any other reason for discontinuation of treatment as outlined in Section 3.4.
- Patients will undergo correlative studies as outlined in the study protocol
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab and Everolimus | Experimental | Drug: Bevacizumab, Drug: Everolimus10 mg Everolimus(RAD001) daily by mouth, days 1-28 10 mg/kg intravenous bevacizumab given days 1 and 15 of each cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must have histologically confirmed adenocarcinoma of the colon or rectum that has progressed on, or patient could not tolerate, fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab and/or panitumumab chemotherapy. Disease must be measurable or evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- Patients must not have had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to study day 1. Patients must not have had major surgery within the 28 days prior to study day 1 or minor surgical procedures within the 7 days prior to study day 1.
- Age >18 years.
- Karnofsky performance status > 70 percent
- Life expectancy of at least 3 months.
Key exclusion criteria (26 listed)
- Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within the 28 days prior to day 1 of the study.
- Patients who have received any other investigational agents within the 28 days prior to day 1 of the study.
- Patients with known central nervous system (CNS) metastases.
- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg). Initiation of antihypertensive is permitted provided adequate control is documented over at least 1 week before starting treatment.
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
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 |
|---|---|---|
| BevacizumabAlso: Avastin10 mg/kg intravenous bevacizumab given days 1 and 15 of each cycle | Drug | Bevacizumab and Everolimus |
| EverolimusAlso: RAD00110 mg Everolimus(RAD001) daily by mouth, days 1-28 | Drug | Bevacizumab and Everolimus |
Primary outcome
Overall Response
Time frame: Measured 1 month after the last treated subject came off treatment
Overall response is composed of complete responses and partial responses. Complete response (CR): disappearance of all target lesions; Partial response: at least a 30 percent decrease in the sum of the longest diameter of the target lesions taking as reference the baseline sum longest diameter. Response is assessed at each subject's restaging, approximately ever 2 months.
Progression Free Survival (PFS)
Time frame: interval between start of treatment and 8-week
8 week PFS
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab and Everolimus in people with Colorectal Adenocarcinoma, run by Herbert Hurwitz 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?
The sponsor lists 8 inclusion and 26 exclusion criteria. 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 27 Dec 2012. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response (time frame: Measured 1 month after the last treated subject came off treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Dec 2012.