Bortezomib and Bevacizumab ("BB-mib-mab") in Patients With Advanced or Recurrent Renal Cell Cancer (RCC)
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Colorectal Cancer, Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | August 2005 |
| End Date: | June 2017 |
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.
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.
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
We found this trial at
1
site
Click here to add this to my saved trials
