Advanced MalignancyPhase 1NCT00428545
Bevacizumab and Bortezomib in Patients With Advanced Malignancy
A Phase 1 study testing Bevacizumab and Bortezomib in people with Advanced Malignancy and Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the highest tolerable dose of Avastin™ (bevacizumab) and Velcade™ (bortezomib) that can be given in combination to patients with a metastatic or unresectable advanced malignancy. The safety and effectiveness of this drug combination will also be studied. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Advanced Malignancy, Lymphoma, Myeloma
- What is being tested?
- Bevacizumab and Bortezomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Nov 2012
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months.
- Patients must be >/= 6 weeks beyond treatment with nitrosoureas or mitomycin-C, >/= 4 weeks beyond other chemo- or radiotherapy, and must have recovered to </= grade 1 toxicity for any treatment-limiting toxicity of prior therapy. (Exception: patients who received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, ribs, sternum, scapulae, vertebrae or skull were not included in the radiotherapy field). Patients who have received non-chemotherapeutic biologic agents must wait 5 half-lives or 4 weeks, whichever is shorter, from the last day of treatment.
- The Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%).
- Patients must have normal organ and marrow function defined as: leukocytes >/= 3,000/mL; absolute neutrophil count >/= 1,500/mL; platelets >/=75,000/mL; creatinine </= 2 * Upper Limits of Normal (ULN); total bilirubin </= 2.0; alanine aminotransferase (ALT or SGPT) </= 3 * ULN; Exception for patients with liver metastasis: total bilirubin </= 3 * ULN; ALT(SGPT) </= 5 * ULN.
- The effects of bevacizumab on the developing human fetus are unknown. Angiogenesis is of critical importance to fetal development, and bevacizumab is likely to have adverse consequences in terms of fetal development. For this reason, 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, for the duration of study participation, and for 30 days after the last dose.
- Ability to understand and the willingness to sign a written informed consent document.
- Life expectancy of at least 3 months.
Who cannot join
- Patients with hemoptysis within 28 days prior to entering the study.
- Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
- Uncontrolled systemic vascular hypertension.
- Patients with clinically significant cardiovascular disease, including: history of cerebrovascular accident (CVA) within 6 months, myocardial infarction or unstable angina within 6 months, unstable angina pectoris.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
- Pregnant or lactating women.
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- History of hypersensitivity to bevacizumab, murine products, or any component of the formulation.
- History of hypersensitivity to bortezomib, boron, mannitol, or any component of the formulation.
- (Only for the 10-patient expansion cohort after identification of the MTD): Patients must be willing to undergo biopsy before treatment and at the end of cycle 1.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Trial of Bevacizumab and Bortezomib in Patients With Advanced Malignancy
The goal of this clinical research study is to find the highest tolerable dose of Avastin™ (bevacizumab) and Velcade™ (bortezomib) that can be given in combination to patients with a metastatic or unresectable advanced malignancy. The safety and effectiveness of this drug combination will also be studied.
Read the detailed description
Bevacizumab is an anti-cancer drug designed to prevent or slow down the growth of cancer cells by blocking blood vessels that supply nutrients necessary for tumor growth.
Bortezomib is an anti-cancer drug designed to block the proteins needed for tumor growth. This may cause cancer cells to die.
If you are found to be eligible to take part in this study, you will be enrolled into a group of about 6 participants. The first group of participants will receive the lowest dose of bevacizumab and bortezomib combined. The next group of participants will receive the next highest dose of bevacizumab and bortezomib combined. This process will continue until the study doctor finds the highest dose that can be tolerated. The dose that you receive will depend on when you are enrolled in this study and the safety data that is available at that time. The dose of bevacizumab and bortezomib that you receive may be lowered if you do not tolerate the study drug combination well. You will not receive any doses of the study drug higher than the dose you are first assigned to.
Bevacizumab and bortezomib will be given in "cycles." Cycles will be about 21 days long or longer, depending on any side effects you may experience. During Cycle 1, Day 1, you will receive bevacizumab by vein over 90 minutes. If bevacizumab is well tolerated in Cycle 1, it will given over 60 minutes in Cycle 2. If it is well tolerated in Cycle 2, it will be given over 30 minutes in Cycle 3. It will continue to be given over 30 minutes in further cycles as long as the drug is still being well tolerated. Depending on which dose level you are assigned to, you will receive bortezomib on Days 1 and 8, or on Days 1, 4, 8, and 11. You will receive bortezomib by vein over about 1-5 minutes.
You will have blood drawn (about 1 tablespoon each time) for routine tests once a week during Cycle 1. You will have a physical exam sometime between Days 7 to 14 during Cycle 1. During the rest of the cycles, you will have a physical exam and blood drawn (about 1 tablespoon each time) for routine tests once every 3 weeks. The status of the disease will be measured by a CT or MRI scan after every 2 cycles.
Once the highest tolerable dose (maximum tolerated dose or MTD) of the combination of bevacizumab and bortezomib is found, up to 15 additional participants with advanced cancer will be enrolled to receive that dose, so that researchers can learn more about the effects of the study drugs on the tumor. A tumor biopsy will be required within two weeks before the first treatment and again at the end of the first cycle for those patients. Up to 10 additional patients with kidney cancer will be enrolled to receive the highest tolerable dose. Tumor biopsies are optional for patients with kidney cancer.
You may continue to receive bevacizumab and bortezomib on this study, unless the cancer gets worse or you experience any intolerable side effects.
Once your participation is over in this study, you will receive standard of care follow-up for the disease.
This is an investigational study. Bevacizumab and bortezomib are both FDA approved and commercially available. Bevacizumab is FDA approved for the treatment of colorectal cancer. Bortezomib is FDA approved for the treatment of multiple myeloma. The combination use of bevacizumab and bortezomib is investigational and authorized for use in research only.
Up to 111 patients will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Advanced Malignancy, Lymphoma, Myeloma, Solid Tumors
- Being tested
- Bevacizumab, Bortezomib
- Keywords
- Advanced Malignancy, Lymphoma, Myeloma, Solid Tumors, Bevacizumab, Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF, Bortezomib, Velcade, PS-341, LDP-341, MLN341
- Medical subject headings
- Lymphoma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF
Starting Dose 2.5 mg/kg By Vein On Day 1 Every 21 Days
BortezomibDrug
Also called Velcade, PS-341, LDP-341, MLN341
Starting Dose 0.7 mg/m^2 By Vein On Days 1 and 8 Every 21 Days
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab + Bortezomib | Experimental | Bevacizumab starting Dose 2.5 mg/kg By Vein On Day 1 Every 21 Days. Bortezomib starting Dose 0.7 mg/m^2 By Vein On Days 1 and 8 Every 21 Days. Receives: Drug: Bevacizumab; Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) and Dose-limiting toxicities (DLT) of Combination Treatment with Bevacizumab and Bortezomib
The MTD is defined as the highest dose studied in which the incidence of DLT was less than 33%.
Measured: Weekly during 21 Day Cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2007 (estimated)
- Study startJan 2007
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced MalignancyStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- 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
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gerald Falchook, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00428545
- Sponsor's protocol ID
- 2006-0764
- Status last verified
- Feb 2013
- First submitted
- 26 Jan 2007
- Last updated
- 12 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Bevacizumab and Bortezomib in Patients With Advanced Malignancy
- ClinicalTrials.gov ID
- NCT00428545
- Acronym / sponsor ID
- 2006-0764
- Conditions
- Advanced Malignancy, Lymphoma, Myeloma, Solid Tumors
- Keywords
- Advanced Malignancy, Lymphoma, Myeloma, Solid Tumors, Bevacizumab, Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 30 Jan 2007 (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.
The goal of this clinical research study is to find the highest tolerable dose of Avastin™ (bevacizumab) and Velcade™ (bortezomib) that can be given in combination to patients with a metastatic or unresectable advanced malignancy. The safety and effectiveness of this drug combination will also be studied.
Detailed description
Bevacizumab is an anti-cancer drug designed to prevent or slow down the growth of cancer cells by blocking blood vessels that supply nutrients necessary for tumor growth.
Bortezomib is an anti-cancer drug designed to block the proteins needed for tumor growth. This may cause cancer cells to die.
If you are found to be eligible to take part in this study, you will be enrolled into a group of about 6 participants. The first group of participants will receive the lowest dose of bevacizumab and bortezomib combined. The next group of participants will receive the next highest dose of bevacizumab and bortezomib combined. This process will continue until the study doctor finds the highest dose that can be tolerated. The dose that you receive will depend on when you are enrolled in this study and the safety data that is available at that time. The dose of bevacizumab and bortezomib that you receive may be lowered if you do not tolerate the study drug combination well. You will not receive any doses of the study drug higher than the dose you are first assigned to.
Bevacizumab and bortezomib will be given in "cycles." Cycles will be about 21 days long or longer, depending on any side effects you may experience. During Cycle 1, Day 1, you will receive bevacizumab by vein over 90 minutes. If bevacizumab is well tolerated in Cycle 1, it will given over 60 minutes in Cycle 2. If it is well tolerated in Cycle 2, it will be given over 30 minutes in Cycle 3. It will continue to be given over 30 minutes in further cycles as long as the drug is still being well tolerated. Depending on which dose level you are assigned to, you will receive bortezomib on Days 1 and 8, or on Days 1, 4, 8, and 11. You will receive bortezomib by vein over about 1-5 minutes.
You will have blood drawn (about 1 tablespoon each time) for routine tests once a week during Cycle 1. You will have a physical exam sometime between Days 7 to 14 during Cycle 1. During the rest of the cycles, you will have a physical exam and blood drawn (about 1 tablespoon each time) for routine tests once every 3 weeks. The status of the disease will be measured by a CT or MRI scan after every 2 cycles.
Once the highest tolerable dose (maximum tolerated dose or MTD) of the combination of bevacizumab and bortezomib is found, up to 15 additional participants with advanced cancer will be enrolled to receive that dose, so that researchers can learn more about the effects of the study drugs on the tumor. A tumor biopsy will be required within two weeks before the first treatment and again at the end of the first cycle for those patients. Up to 10 additional patients with kidney cancer will be enrolled to receive the highest tolerable dose. Tumor biopsies are optional for patients with kidney cancer.
You may continue to receive bevacizumab and bortezomib on this study, unless the cancer gets worse or you experience any intolerable side effects.
Once your participation is over in this study, you will receive standard of care follow-up for the disease.
This is an investigational study. Bevacizumab and bortezomib are both FDA approved and commercially available. Bevacizumab is FDA approved for the treatment of colorectal cancer. Bortezomib is FDA approved for the treatment of multiple myeloma. The combination use of bevacizumab and bortezomib is investigational and authorized for use in research only.
Up to 111 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab + Bortezomib | Experimental | Drug: Bevacizumab, Drug: BortezomibBevacizumab starting Dose 2.5 mg/kg By Vein On Day 1 Every 21 Days. Bortezomib starting Dose 0.7 mg/m^2 By Vein On Days 1 and 8 Every 21 Days. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months.
- Patients must be >/= 6 weeks beyond treatment with nitrosoureas or mitomycin-C, >/= 4 weeks beyond other chemo- or radiotherapy, and must have recovered to </= grade 1 toxicity for any treatment-limiting toxicity of prior therapy. (Exception: patients who received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, ribs, sternum, scapulae, vertebrae or skull were not included in the radiotherapy field). Patients who have received non-chemotherapeutic biologic agents must wait 5 half-lives or 4 weeks, whichever is shorter, from the last day of treatment.
- The Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%).
- Patients must have normal organ and marrow function defined as: leukocytes >/= 3,000/mL; absolute neutrophil count >/= 1,500/mL; platelets >/=75,000/mL; creatinine </= 2 * Upper Limits of Normal (ULN); total bilirubin </= 2.0; alanine aminotransferase (ALT or SGPT) </= 3 * ULN; Exception for patients with liver metastasis: total bilirubin </= 3 * ULN; ALT(SGPT) </= 5 * ULN.
- The effects of bevacizumab on the developing human fetus are unknown. Angiogenesis is of critical importance to fetal development, and bevacizumab is likely to have adverse consequences in terms of fetal development. For this reason, 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, for the duration of study participation, and for 30 days after the last dose.
Key exclusion criteria (9 listed)
- Patients with hemoptysis within 28 days prior to entering the study.
- Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
- Uncontrolled systemic vascular hypertension.
- Patients with clinically significant cardiovascular disease, including: history of cerebrovascular accident (CVA) within 6 months, myocardial infarction or unstable angina within 6 months, unstable angina pectoris.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
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: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGFStarting Dose 2.5 mg/kg By Vein On Day 1 Every 21 Days | Drug | Bevacizumab + Bortezomib |
| BortezomibAlso: Velcade, PS-341, LDP-341, MLN341Starting Dose 0.7 mg/m^2 By Vein On Days 1 and 8 Every 21 Days | Drug | Bevacizumab + Bortezomib |
Primary outcome
Maximum tolerated dose (MTD) and Dose-limiting toxicities (DLT) of Combination Treatment with Bevacizumab and Bortezomib
Time frame: Weekly during 21 Day Cycle
The MTD is defined as the highest dose studied in which the incidence of DLT was less than 33%.
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 12 Feb 2013.
- UT MD Anderson Cancer Center websiteLink provided by the sponsor.
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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.
Gerald Falchook, MD principal investigator
M.D. Anderson Cancer Center
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 and Bortezomib in people with Advanced Malignancy and Lymphoma, run by M.D. Anderson Cancer Center 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 7 inclusion and 9 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 12 Feb 2013. 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 (MTD) and Dose-limiting toxicities (DLT) of Combination Treatment with Bevacizumab and Bortezomib (time frame: Weekly during 21 Day Cycle). 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 12 Feb 2013.