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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Southern California
Sponsor:
Information provided by (Responsible Party):
University of Southern California
ClinicalTrials.gov Identifier:
NCT00184015
First received: September 12, 2005
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Renal Cell Cancer
Drug: Bevacizumab and Bortezomib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Toxicity [ Time Frame: Toxicity as assessed by CTCAE 3.0 undertaken every 3 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • response [ Time Frame: Every 9 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 46
Study Start Date: August 2005
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00184015

Contacts
Contact: Charlean Ketchens, RN 323-226-2452 ketchens_c@ccnt.hsc.usc.edu

Locations
United States, California
Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Zeno Ashai    323-865-0463    zeno.ashai@med.usc.edu   
Sponsors and Collaborators
University of Southern California
Investigators
Principal Investigator: David Quinn, MD, PhD University of Southern California
  More Information

No publications provided

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT00184015     History of Changes
Other Study ID Numbers: 4K-05-1
Study First Received: September 12, 2005
Last Updated: May 20, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Bevacizumab
Bortezomib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 31, 2014