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Bortezomib and Bevacizumab ("BB-mib-mab") in Patients With Advanced or Recurrent Renal Cell Cancer (RCC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00184015
Recruitment Status : Unknown
Verified April 2017 by University of Southern California.
Recruitment status was:  Active, not recruiting
First Posted : September 16, 2005
Last Update Posted : April 11, 2017
Information provided by (Responsible Party):
University of Southern California

Brief Summary:

This research study is for subjects with cancer of the kidney (also known as renal cell carcinoma) that cannot be treated with surgery. The purpose of this study is to see if the combination of bevacizumab and bortezomib is safe and tolerable and can help people with kidney cancer. The investigators would also like to find out what dose of the study drugs can be used safely and effectively, whether the combination of these two drugs can decrease cancer symptoms and stop tumor growth, and how frequently serious side effects might occur with this combination.

The study will be conducted in two phases-Phase 1 and Phase 2. In Phase 1, subjects will be assigned to a fixed dose of bevacizumab and different strengths of bortezomib given at 2 different schedules. Phase 2 will depend on how subjects tolerate the doses and schedules of bortezomib in Phase 1.

Bortezomib is a type of drug known as a "proteasome inhibitor." By blocking the "proteasome" in cancer cells, bortezomib affects the way these cells divide. Bevacizumab is an inhibitor (blocker) of blood vessel formation. Tumors need blood vessels in order to continue to grow and bevacizumab is thought to work by preventing new blood vessels from growing.

Bortezomib (also called Velcade or PS-341) has been approved by the US Food and Drug Administration (FDA) for the treatment of myeloma, but has not been approved for the treatment of kidney cancer. Bevacizumab (also called Avastin) has been approved by the FDA for the treatment of colon cancer, but has not been approved for the treatment of kidney cancer. However, the FDA is permitting the combined use of bortezomib and bevacizumab in this research study.

The bevacizumab that will be given in this study is not a commercially marketed product. Although it is expected to be very similar in safety and activity to the commercially available drug, it is possible that some differences may exist. Because this is not a commercially marketed drug, bevacizumab can only be administered to subjects enrolled in this study and may only be administered under the direction of physicians who are investigators in this study.

Approximately 40-52 subjects will take part in this study.

Condition or disease Intervention/treatment Phase
Renal Cell Cancer Drug: Bevacizumab and Bortezomib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Actual Study Start Date : August 18, 2005
Actual Primary Completion Date : August 21, 2016
Estimated Study Completion Date : August 21, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Schedule A Drug: Bevacizumab and Bortezomib
Bevacizumab 15 mg/kg on day 1 with Bortezomib 1.0 or 1.3 mg/m2 on days 1, 4, 8 and 11 every 21 days

Experimental: Schedule B Drug: Bevacizumab and Bortezomib
Bevacizumab 15 mg/kg on day 1 with Bortezomib 1.6 or 1.8 mg/m2 on days 1 and 8 every 21 days

Primary Outcome Measures :
  1. Toxicity [ Time Frame: Toxicity as assessed by CTCAE 3.0 undertaken every 3 weeks ]

Secondary Outcome Measures :
  1. response [ Time Frame: Every 9 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Distant metastatic (TX NX M1) or locally recurrent renal cell carcinoma not amenable to cure by surgical or other means
  • Measurable or non-measurable (evaluable) disease either on imaging scan or physical examination
  • Pathological confirmation of the diagnosis of renal cell carcinoma either during prior nephrectomy or by biopsy of a primary or metastatic lesion - provision of a paraffin-embedded tissue block to confirm the diagnosis and allow molecular correlate assessment is required.
  • ECOG performance status 0 or 1.
  • Patients must have an AGC of greater than or equal to 1,500/mm3 and a platelet count of greater than or equal to 100,000/mm3. These tests must be obtained within 28 days of registration.
  • Patients must have a calculated or measured creatinine clearance greater than or equal to 40 ml/min obtained within 28 days prior to registration.
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
  • Male subject agrees to use an acceptable method of contraception for the duration of the study.
  • May have been treated with interleukin and/or interferon but must not have had more than one line of prior cytotoxic chemotherapy
  • May have had up to one biologic therapy provided they have not had bortezomib or bevacizumab
  • May have had up to 2 prior vaccine therapies
  • May have been treated with radiation therapy, provided there are measurable or evaluable lesions outside the field of radiation
  • May have had radiation provided the patient has recovered from the side effects of the therapy (typically 2 weeks after final fraction) and less than 30% of the total bone marrow has been irradiated

Exclusion Criteria:

  • Brain metastases or history of brain metastases
  • History of deep vein thrombosis or thromboembolic disease within 1 year or requiring ongoing anticoagulant therapy
  • History of stroke or myocardial infarction within six months
  • Other major illnesses likely to limit survival including poorly controlled hypertension (BP > 150/100 mmHg) or symptomatic or clinically significant peripheral vascular disease or angina pectoris
  • Unstable angina
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • Urine protein:creatinine ratio greater than or equal to 1.0 at screening
  • Evidence of bleeding diathesis or coagulopathy.
  • Major surgical procedure, open biopsy, significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study
  • Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0
  • Pregnant (positive pregnancy test) or lactating; confirmation that female subject is not pregnant by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  • Inability to comply with study and/or follow-up procedures
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to Day 0
  • Serious, non-healing wound, ulcer, or bone fracture
  • Neuropathy at baseline > grade 1
  • Patient has received other investigational drugs within 14 days before enrollment
  • Patient has hypersensitivity to bevacizumab, bortezomib, boron or mannitol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00184015

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United States, California
Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Sponsors and Collaborators
University of Southern California
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Principal Investigator: David Quinn, MD, PhD University of Southern California
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Responsible Party: University of Southern California Identifier: NCT00184015    
Other Study ID Numbers: 4K-05-1
First Posted: September 16, 2005    Key Record Dates
Last Update Posted: April 11, 2017
Last Verified: April 2017
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors