Bevacizumab and Bortezomib in Patients With Advanced Malignancy

February 11, 2013 updated by: M.D. Anderson Cancer Center

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
104

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • UT MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 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.
  2. 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.
  3. The Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%).
  4. 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.
  5. 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.
  6. Ability to understand and the willingness to sign a written informed consent document.
  7. Life expectancy of at least 3 months.

Exclusion Criteria:

  1. Patients with hemoptysis within 28 days prior to entering the study.
  2. Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
  3. Uncontrolled systemic vascular hypertension.
  4. 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.
  5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
  6. Pregnant or lactating women.
  7. History of hypersensitivity to bevacizumab, murine products, or any component of the formulation.
  8. History of hypersensitivity to bortezomib, boron, mannitol, or any component of the formulation.
  9. (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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Bevacizumab + Bortezomib
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.
Drug: Bevacizumab
Starting Dose 2.5 mg/kg By Vein On Day 1 Every 21 Days
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Bortezomib
Starting Dose 0.7 mg/m^2 By Vein On Days 1 and 8 Every 21 Days
Other Names:
  • Velcade
  • MLN341
  • PS-341
  • LDP-341

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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%.
Weekly during 21 Day Cycle

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
M.D. Anderson Cancer Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gerald Falchook, MD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 26, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 30, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 12, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 11, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2006-0764

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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