Renal Cell CarcinomaPhase 2NCT00923130
Bevacizumab Plus Ixabepilone to Treat Patients With Advanced Kidney Cancer
A Phase 2 study testing Bevacizumab and Ixabepilone in people with Renal Cell Carcinoma, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
Background: Substantial preclinical antitumor synergy supports the exploration of the combination of antiangiogenic compounds (including sunitinib and bevacizumab) plus ixabepilone. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Bevacizumab and Ixabepilone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- 7 Jan 2009to Jun 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects meeting all of the following criteria will be considered for enrollment into the study:
- Pathologic confirmation of metastatic or unsectable renal cell carcinoma with predominant clear cell histology (greater than 70%) by the Laboratory of Pathology, National Cancer Institute (NCI) or the Medical University of South Carolina..
- Progression on or after stopping treatment with an agent approved by the Food and Drug Administration (FDA) for the treatment of renal cell carcinoma (RCC). Patients must have received at least one FDA approved agent (axitinib, sunitinib, sorafenib, pazopanib, temsirolimus, interleukin-2 (IL-2), interferon or everolimus). Patients must be off prior IL-2 or interferon for 4 weeks prior to entry. They must be off sunitinib, sorafenib, pazopanib, axitinib, temsirolimus or everolimus or other tyrosine kinase inhibitor (TKIs) for 2 weeks prior to entry.
- Eighteen years of age or older.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
- Resolution of any toxic effects of prior therapy (except alopecia) to NCI Common Terminology Criteria in Solid Tumors (CTCAE) v.3.0 through 12/31/10 and version 4.0 beginning 1/1/11 grade less than or equal to 1 and to baseline laboratory values as defined in inclusion criterion # 6.
Show all 19Show fewer
- Adequate organ and bone marrow function as evidenced by:
- hemoglobin greater than or equal to 9.0 g/dL
- absolute neutrophil count greater than or equal to 1.5 x 10(9)/L
- platelet count greater than or equal to 100 x 10(9)/L
- creatinine less than or equal to 1.5 times the ULN, OR measured creatinine clearance greater than or equal to 40 ml/min
- urine proteinuria less than 20mg/dL on random protein creatinine ratio urine samples or a 24-hour urine protein less than 500 mg. NOTE: If on a random protein creatinine ratio the urine protein is greater that or equal to 20mg/dL, then obtain a 24 hour urine collection to accurately demonstrate that the 24 hour total is less than 500 mg/24 hours.
- aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 times the upper limit of normal (ULN) (or less than or equal to 5 times the ULN if liver function abnormalities due to underlying malignancy)
- total bilirubin less than or equal to 1.5 times the ULN
- Subjects must be postmenopausal, surgically sterile, or using effective contraception. All female subjects of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment. Effective contraception includes hormonal or barrier methods.
- No other invasive malignancies within the past two years (with the exception of nonmelanoma skin cancers, non-invasive bladder cancer, stage I endometrial cancer or cervical cancer).
- Subjects must agree to sign and date an Institutional Review Board (IRB)-approved subject informed consent form.
- Subjects must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
- Patients must have measurable disease either by conventional imaging or clinical examination.
Who cannot join
- Subjects presenting with any of the following will not be included in the study:
- Invasive procedures defined as follows:
- Major surgical procedure, open biopsy or significant traumatic injury within 6 weeks prior to Day 1 therapy
- Anticipation of need for major surgical procedures during the course of the study
- Minor surgery, such as port-a-cath placement, and dental procedures, within 2 weeks.
- (There will be no delay for percutaneous core biopsies or peripherally inserted central catheter (PICC)/internal jugular (IJ) line placement)
Show all 24Show fewer
- Cumulative radiation therapy to greater than 25% of the total bone marrow.
- History of uncontrolled or labile hypertension, defined as blood pressure greater than 160/90 mm Hg (NCI CTCAE v.3.0 through 12/31/10 and version 4.0 beginning 1/1/11 grade greater than or equal to 2), on at least 2 repeated determinations on separate days within 15 days prior to study enrollment.
- Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure; cerebrovascular accident or transient ischemic attack, grade greater than or equal to 2 peripheral neuropathy, peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, or other thromboembolic event.
- Symptomatic spinal cord compression.
- Evidence of clinically significant bleeding diathesis or underlying coagulopathy.
- Antiretroviral therapy for human immunodeficiency virus (HIV) disease.
- Pregnant (positive pregnancy test) or nursing women. Both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 6 months after the completion of bevacizumab therapy.
- Other severe acute or chronic medical or psychiatric condition, or significant laboratory abnormality requiring further investigation that may cause undue risk for the subjects safety, 18 inhibit protocol participation, or interfere with interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
- Prior therapy with bevacizumab
- Prior therapy with ixabepilone.
- Patients on anticoagulant therapy will be evaluated on a case by case basis for inclusion.
- Serious or non-healing wound, ulcer or bone fracture
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1
- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
- Known central nervous system (CNS) disease except for treated brain metastasis.
- -Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (magnetic resonance imaging (MRI) or computed tomography (CT)). (Stable dose of anticonvulsants are allowed). Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear particle accelerator (LINAC), or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
- Patients with known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies
- Patients receiving cytochrome P450 3A4 (CYP3A4) inhibitors in section 3.6 that cannot be discontinued.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
University of South Carolina
Charleston, South Carolina, 29425
About this study
Official title: A Phase II Multi-Center Study of Bevacizumab in Combination With Ixabepilone in Subjects With Advanced Renal Cell Carcinoma
Background:
- Substantial preclinical antitumor synergy supports the exploration of the combination of antiangiogenic compounds (including sunitinib and bevacizumab) plus ixabepilone. In Vivo, synergistic activity between ixabepilone and bevacizumab has been demonstrated using the 151-B human renal carcinoma xenograft model and this synergy compares favorably with other antiangiogenic inhibitors (i.e. sunitinib).
- Combination therapies of bevacizumab with chemotherapy demonstrated improved benefit compared with single-agent cytotoxics in multiple animal models and in humans.
- Clinical activity of both compounds used as single agents has been demonstrated in a broad spectrum of solid tumors. Bevacizumab and ixabepilone, when used as a single agent, have demonstrated substantial activity in renal cell carcinoma.
- Phase II studies with bevacizumab and ixabepilone suggest the absence of overlapping toxicities.
- Development of a well-tolerated and active bevacizumab/ixabepilone combination has the potential to further improve the treatment of metastatic renal cell carcinoma (mRCC), and could represent a second-line option after sunitinib or sorafenib are no longer of benefit or are intolerable.
Read more
Primary Objectives:
- Determine the objective response rate of the combination of ixabepilone and bevacizumab in patients with relapsed or refractory mRCC.
- Determine progression-free survival.
- Characterize the toxicity of the combination of ixabepilone and bevacizumab in patients with mRCC.
- Determine changes in biomarkers and evaluate correlation with clinical outcomes.
Eligibility:
- Pathologic confirmation of renal cell carcinoma (clear cell histology) by the Laboratory of Pathology, National Cancer Institute (NCI), or the Medical University of South Carolina.
- Presence of metastatic renal carcinoma, after progression or intolerance to Vascular endothelial growth factor receptor (VEGFR) inhibitors (sunitinib and/or sorafenib).
- Adequate organ and bone marrow function.
Design:
- Multi-center, open labeled phase II study
- Following a Simon two-stage optimal design, a maximum of 58 patients with metastatic RCC will be accrued.
- Ixabepilone will be administered daily as a one hour infusion on five successive days (daily x 5), every three weeks (one cycle equals 3 weeks or 21 days +/- 5 days). Following cycle 6, cycles will be spread out to 4 weeks or 28 days +/- 5 days. The starting dose will be a daily dose of 6 mg/m(2)/day, for a total per cycle dose of 30 mg/m(2).
- In addition, 15 mg/kg bevacizumab will be administered intravenously on day 1 of each cycle. The first infusion of bevacizumab will be 90 minutes in duration, the second 60 minutes in duration, and in all subsequent cycles bevacizumab will be infused over 30 minutes if prior infusions are well tolerated.
Read the detailed description
Background:
- Substantial preclinical antitumor synergy supports the exploration of the combination of antiangiogenic compounds (including sunitinib and bevacizumab) plus ixabepilone. In Vivo, synergistic activity between ixabepilone and bevacizumab has been demonstrated using the 151-B human renal carcinoma xenograft model and this synergy compares favorably with other antiangiogenic inhibitors (i.e. sunitinib).
- Combination therapies of bevacizumab with chemotherapy demonstrated improved benefit compared with single-agent cytotoxics in multiple animal models and in humans.
- Clinical activity of both compounds used as single agents has been demonstrated in a broad spectrum of solid tumors. Bevacizumab and ixabepilone, when used as a single agent, have demonstrated substantial activity in renal cell carcinoma.
- Phase II studies with bevacizumab and ixabepilone suggest the absence of overlapping toxicities.
- Development of a well-tolerated and active bevacizumab/ixabepilone combination has the potential to further improve the treatment of metastatic renal cell carcinoma (mRCC), and could represent a second-line option after sunitinib or sorafenib are no longer of benefit or are intolerable.
Primary Objectives:
- Determine the objective response rate of the combination of ixabepilone and bevacizumab in patients with relapsed or refractory mRCC.
- Determine progression-free survival.
- Characterize the toxicity of the combination of ixabepilone and bevacizumab in patients with mRCC.
- Determine changes in biomarkers and evaluate correlation with clinical outcomes.
Eligibility:
- Pathologic confirmation of renal cell carcinoma (clear cell histology) by the Laboratory of Pathology, National Cancer Institute (NCI), or the Medical University of South Carolina.
- Presence of metastatic renal carcinoma, after progression or intolerance to vascular endothelial growth factor receptor (VEGFR) inhibitors (sunitinib and/or sorafenib).
- Adequate organ and bone marrow function.
Design:
- Multi-center, open labeled phase II study
- Following a Simon two-stage optimal design, a maximum of 58 patients with metastatic RCC will be accrued.
- Ixabepilone will be administered daily as a one hour infusion on five successive days (daily x 5), every three weeks (one cycle equals 3 weeks or 21 days +/- 5 days). Following cycle 6, cycles will be spread out to 4 weeks or 28 days +/- 5 days. The starting dose will be a daily dose of 6 mg/m(2)/day, for a total per cycle dose of 30 mg/m(2).
- In addition, 15 mg/kg bevacizumab will be administered intravenously on day 1 of each cycle. The first infusion of bevacizumab will be 90 minutes in duration, the second 60 minutes in duration, and in all subsequent cycles bevacizumab will be infused over 30 minutes if prior infusions are well tolerated.
- Conditions
- Renal Cell Carcinoma
- Being tested
- Bevacizumab, Ixabepilone
- Keywords
- Renal Cell Carcinoma, Bevacizumab, Ixabepilone, Phase II
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
Bevacizumab will be administered intravenously every 3 weeks on an outpatient basis with the exception of admissions for the purpose of facilitating research studies. The dose of bevacizumab to be given is 15 mg/kg.
IxabepiloneDrug
Also called Ixempra
Ixabepilone will be given on days 1, 2, 3, 4, and 5 of each three week cycle as a one hour intravenous infusion. The dose will be 6 mg/m(2)/day on five successive days.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab with Ixabepilone | Experimental | Bevacizumab 15mg/kg every 3 weeks Ixabepilone given on days 1,2,3,4 and 5 of each three week cycle at a dose of 6mg/m(2)/day Receives: Drug: Bevacizumab; Drug: Ixabepilone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
The time between the first day of treatment to the day of disease progression. Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Measured: up to 44 months
Secondary outcomes (4)
Number of Participants With an Objective Response (Complete Response (CR) or Partial Response (PR)) Per the Response Evaluation Criteria in Solid Tumors (RECIST)
Response (complete response (CR) and partial response (PR)) was measured by the RECIST. Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Measured: Two Years
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For the detailed list of adverse events, see the adverse event module. Adverse events are assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Measured: Date treatment consent signed to date off study, approximately 84 months and 25 days
Number of Participants Who Had Biopsies
To obtain tumor tissue and perform analysis for molecular changes in the tumor before and after a cycle of chemotherapy.
Measured: Baseline and Cycle 2 Day 1
Overall Survival
Time between the first day of treatment and the day of death.
Measured: Time between the first day of treatment and the day of death, assessed up to approximately 7 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2009 (estimated)
- Study start7 Jan 2009
- Primary completion1 Mar 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Ravi A. Madan, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Ravi A Madan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00923130
- Sponsor's protocol ID
- 090057
- Other IDs
- 09-C-0057
- Status last verified
- Mar 2018
- First submitted
- 17 Jun 2009
- Last updated
- 17 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ryan AM, Eppler DB, Hagler KE, Bruner RH, Thomford PJ, Hall RL, Shopp GM, O'Neill CA. Preclinical safety evaluation of rhuMAbVEGF, an antiangiogenic humanized monoclonal antibody. Toxicol Pathol. 1999 Jan-Feb;27(1):78-86. doi: 10.1177/019262339902700115.
PubMed 10367678Ferrara N, Chen H, Davis-Smyth T, Gerber HP, Nguyen TN, Peers D, Chisholm V, Hillan KJ, Schwall RH. Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat Med. 1998 Mar;4(3):336-40. doi: 10.1038/nm0398-336.
PubMed 9500609Hellman S, Rosenthal DS, Moloney WC, Chaffey JT. The treatment of non-Hodgkin's lymphoma. Cancer. 1975 Aug;36(2):804-8. doi: 10.1002/1097-0142(197508)36:2+3.0.co;2-w.
PubMed 1157038Phase II clinicaltrial of bevacizumab plus ixabepilone in renal cell carcinoma. Mauricio Emmanuel Burotto Pichun, Nicolas Acquavella, Maureen Edgerly, Susan Elaine Bates, Sanjeeve Balasubramaniam and Antonio Tito Fojo; Journal of Clinical Oncology, 2014 Genitourinary Cancers Symposium (January 30 - February 1, 2014). Vol. 32, No 4_suppl (February 1 Supplement), 2014: 427
Burotto M, Edgerly M, Velarde M, Balasubramaniam S, Drabkin H, Gormaz JG, O'Sullivan C, Madan R, Fojo T. A Phase II Multi-Center Study of Bevacizumab in Combination with Ixabepilone in Subjects with Advanced Renal Cell Carcinoma. Oncologist. 2017 Aug;22(8):888-e84. doi: 10.1634/theoncologist.2017-0211. Epub 2017 Jul 5.
PubMed 28679644
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Multi-Center Study of Bevacizumab in Combination With Ixabepilone in Subjects With Advanced Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT00923130
- Acronym / sponsor ID
- 090057
- Conditions
- Renal Cell Carcinoma
- Keywords
- Renal Cell Carcinoma, Bevacizumab, Ixabepilone, Phase II
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 7 Jan 2009 (actual)
- Primary completion
- 1 Mar 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 18 Jun 2009 (estimated)
- Results
- Posted 27 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Substantial preclinical antitumor synergy supports the exploration of the combination of antiangiogenic compounds (including sunitinib and bevacizumab) plus ixabepilone. In Vivo, synergistic activity between ixabepilone and bevacizumab has been demonstrated using the 151-B human renal carcinoma xenograft model and this synergy compares favorably with other antiangiogenic inhibitors (i.e. sunitinib).
- Combination therapies of bevacizumab with chemotherapy demonstrated improved benefit compared with single-agent cytotoxics in multiple animal models and in humans.
- Clinical activity of both compounds used as single agents has been demonstrated in a broad spectrum of solid tumors. Bevacizumab and ixabepilone, when used as a single agent, have demonstrated substantial activity in renal cell carcinoma.
- Phase II studies with bevacizumab and ixabepilone suggest the absence of overlapping toxicities.
- Development of a well-tolerated and active bevacizumab/ixabepilone combination has the potential to further improve the treatment of metastatic renal cell carcinoma (mRCC), and could represent a second-line option after sunitinib or sorafenib are no longer of benefit or are intolerable.
Primary Objectives:
- Determine the objective response rate of the combination of ixabepilone and bevacizumab in patients with relapsed or refractory mRCC.
- Determine progression-free survival.
- Characterize the toxicity of the combination of ixabepilone and bevacizumab in patients with mRCC.
- Determine changes in biomarkers and evaluate correlation with clinical outcomes.
Eligibility:
- Pathologic confirmation of renal cell carcinoma (clear cell histology) by the Laboratory of Pathology, National Cancer Institute (NCI), or the Medical University of South Carolina.
- Presence of metastatic renal carcinoma, after progression or intolerance to Vascular endothelial growth factor receptor (VEGFR) inhibitors (sunitinib and/or sorafenib).
- Adequate organ and bone marrow function.
Design:
- Multi-center, open labeled phase II study
- Following a Simon two-stage optimal design, a maximum of 58 patients with metastatic RCC will be accrued.
- Ixabepilone will be administered daily as a one hour infusion on five successive days (daily x 5), every three weeks (one cycle equals 3 weeks or 21 days +/- 5 days). Following cycle 6, cycles will be spread out to 4 weeks or 28 days +/- 5 days. The starting dose will be a daily dose of 6 mg/m(2)/day, for a total per cycle dose of 30 mg/m(2).
- In addition, 15 mg/kg bevacizumab will be administered intravenously on day 1 of each cycle. The first infusion of bevacizumab will be 90 minutes in duration, the second 60 minutes in duration, and in all subsequent cycles bevacizumab will be infused over 30 minutes if prior infusions are well tolerated.
Detailed description
Background:
- Substantial preclinical antitumor synergy supports the exploration of the combination of antiangiogenic compounds (including sunitinib and bevacizumab) plus ixabepilone. In Vivo, synergistic activity between ixabepilone and bevacizumab has been demonstrated using the 151-B human renal carcinoma xenograft model and this synergy compares favorably with other antiangiogenic inhibitors (i.e. sunitinib).
- Combination therapies of bevacizumab with chemotherapy demonstrated improved benefit compared with single-agent cytotoxics in multiple animal models and in humans.
- Clinical activity of both compounds used as single agents has been demonstrated in a broad spectrum of solid tumors. Bevacizumab and ixabepilone, when used as a single agent, have demonstrated substantial activity in renal cell carcinoma.
- Phase II studies with bevacizumab and ixabepilone suggest the absence of overlapping toxicities.
- Development of a well-tolerated and active bevacizumab/ixabepilone combination has the potential to further improve the treatment of metastatic renal cell carcinoma (mRCC), and could represent a second-line option after sunitinib or sorafenib are no longer of benefit or are intolerable.
Primary Objectives:
- Determine the objective response rate of the combination of ixabepilone and bevacizumab in patients with relapsed or refractory mRCC.
- Determine progression-free survival.
- Characterize the toxicity of the combination of ixabepilone and bevacizumab in patients with mRCC.
- Determine changes in biomarkers and evaluate correlation with clinical outcomes.
Eligibility:
- Pathologic confirmation of renal cell carcinoma (clear cell histology) by the Laboratory of Pathology, National Cancer Institute (NCI), or the Medical University of South Carolina.
- Presence of metastatic renal carcinoma, after progression or intolerance to vascular endothelial growth factor receptor (VEGFR) inhibitors (sunitinib and/or sorafenib).
- Adequate organ and bone marrow function.
Design:
- Multi-center, open labeled phase II study
- Following a Simon two-stage optimal design, a maximum of 58 patients with metastatic RCC will be accrued.
- Ixabepilone will be administered daily as a one hour infusion on five successive days (daily x 5), every three weeks (one cycle equals 3 weeks or 21 days +/- 5 days). Following cycle 6, cycles will be spread out to 4 weeks or 28 days +/- 5 days. The starting dose will be a daily dose of 6 mg/m(2)/day, for a total per cycle dose of 30 mg/m(2).
- In addition, 15 mg/kg bevacizumab will be administered intravenously on day 1 of each cycle. The first infusion of bevacizumab will be 90 minutes in duration, the second 60 minutes in duration, and in all subsequent cycles bevacizumab will be infused over 30 minutes if prior infusions are well tolerated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab with Ixabepilone | Experimental | Drug: Bevacizumab, Drug: IxabepiloneBevacizumab 15mg/kg every 3 weeks Ixabepilone given on days 1,2,3,4 and 5 of each three week cycle at a dose of 6mg/m(2)/day |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Subjects meeting all of the following criteria will be considered for enrollment into the study:
- Pathologic confirmation of metastatic or unsectable renal cell carcinoma with predominant clear cell histology (greater than 70%) by the Laboratory of Pathology, National Cancer Institute (NCI) or the Medical University of South Carolina..
- Progression on or after stopping treatment with an agent approved by the Food and Drug Administration (FDA) for the treatment of renal cell carcinoma (RCC). Patients must have received at least one FDA approved agent (axitinib, sunitinib, sorafenib, pazopanib, temsirolimus, interleukin-2 (IL-2), interferon or everolimus). Patients must be off prior IL-2 or interferon for 4 weeks prior to entry. They must be off sunitinib, sorafenib, pazopanib, axitinib, temsirolimus or everolimus or other tyrosine kinase inhibitor (TKIs) for 2 weeks prior to entry.
- Eighteen years of age or older.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
Key exclusion criteria (24 listed)
- Invasive procedures defined as follows:
- Cumulative radiation therapy to greater than 25% of the total bone marrow.
- History of uncontrolled or labile hypertension, defined as blood pressure greater than 160/90 mm Hg (NCI CTCAE v.3.0 through 12/31/10 and version 4.0 beginning 1/1/11 grade greater than or equal to 2), on at least 2 repeated determinations on separate days within 15 days prior to study enrollment.
- Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure; cerebrovascular accident or transient ischemic attack, grade greater than or equal to 2 peripheral neuropathy, peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, or other thromboembolic event.
- Symptomatic spinal cord compression.
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: AvastinBevacizumab will be administered intravenously every 3 weeks on an outpatient basis with the exception of admissions for the purpose of facilitating research studies. The dose of bevacizumab to be given is 15 mg/kg. | Drug | Bevacizumab with Ixabepilone |
| IxabepiloneAlso: IxempraIxabepilone will be given on days 1, 2, 3, 4, and 5 of each three week cycle as a one hour intravenous infusion. The dose will be 6 mg/m(2)/day on five successive days. | Drug | Bevacizumab with Ixabepilone |
Primary outcome
Progression-free Survival
Time frame: up to 44 months
The time between the first day of treatment to the day of disease progression. Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
4 secondary outcomes
Number of Participants With an Objective Response (Complete Response (CR) or Partial Response (PR)) Per the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Two Years
Number of Participants With Adverse Events
Time frame: Date treatment consent signed to date off study, approximately 84 months and 25 days
Number of Participants Who Had Biopsies
Time frame: Baseline and Cycle 2 Day 1
Overall Survival
Time frame: Time between the first day of treatment and the day of death, assessed up to approximately 7 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10367678Ryan AM, Eppler DB, Hagler KE, Bruner RH, Thomford PJ, Hall RL, Shopp GM, O'Neill CA. Preclinical safety evaluation of rhuMAbVEGF, an antiangiogenic humanized monoclonal antibody. Toxicol Pathol. 1999 Jan-Feb;27(1):78-86. doi: 10.1177/019262339902700115.
- Background: PubMed 9500609Ferrara N, Chen H, Davis-Smyth T, Gerber HP, Nguyen TN, Peers D, Chisholm V, Hillan KJ, Schwall RH. Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat Med. 1998 Mar;4(3):336-40. doi: 10.1038/nm0398-336.
- Background: PubMed 1157038Hellman S, Rosenthal DS, Moloney WC, Chaffey JT. The treatment of non-Hodgkin's lymphoma. Cancer. 1975 Aug;36(2):804-8. doi: 10.1002/1097-0142(197508)36:2+3.0.co;2-w.
- Results publicationPhase II clinicaltrial of bevacizumab plus ixabepilone in renal cell carcinoma. Mauricio Emmanuel Burotto Pichun, Nicolas Acquavella, Maureen Edgerly, Susan Elaine Bates, Sanjeeve Balasubramaniam and Antonio Tito Fojo; Journal of Clinical Oncology, 2014 Genitourinary Cancers Symposium (January 30 - February 1, 2014). Vol. 32, No 4_suppl (February 1 Supplement), 2014: 427
- Derived from this study: PubMed 28679644Burotto M, Edgerly M, Velarde M, Balasubramaniam S, Drabkin H, Gormaz JG, O'Sullivan C, Madan R, Fojo T. A Phase II Multi-Center Study of Bevacizumab in Combination with Ixabepilone in Subjects with Advanced Renal Cell Carcinoma. Oncologist. 2017 Aug;22(8):888-e84. doi: 10.1634/theoncologist.2017-0211. Epub 2017 Jul 5.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Ravi A Madan, M.D. principal investigator
National Cancer Institute (NCI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab and Ixabepilone in people with Renal Cell Carcinoma, run by National Cancer Institute (NCI) at 2 sites 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 19 inclusion and 24 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 17 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression-free Survival (time frame: up to 44 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00923130, which also lists 5 linked publications.
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 17 Apr 2018.