Trebananib With or Without Bevacizumab, Pazopanib Hydrochloride, Sorafenib Tosylate, or Sunitinib Malate in Treating Patients With Advanced Kidney Cancer
|Recurrent Renal Cell Carcinoma Stage III Renal Cell Cancer Stage IV Renal Cell Cancer||Biological: Bevacizumab Other: Laboratory Biomarker Analysis Drug: Pazopanib Hydrochloride Other: Pharmacological Study Drug: Sorafenib Tosylate Drug: Sunitinib Malate Biological: Trebananib||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Randomized Phase 2 Study of AMG 386 With or Without Continued Anti-vascular Endothelial Growth Factor (VEGF) Therapy in Patients With Renal Cell Carcinoma Who Have Progressed on Bevacizumab, Pazopanib, Sorafenib, or Sunitinib|
- Overall tumor response rate, defined as the total number of efficacy-evaluable patients who achieve a complete or partial response by Response Evaluation Criteria in Solid Tumors version 1.1 criteria [ Time Frame: Up to 8 weeks ]Best response will be listed for each patient and summarized using standard descriptive methods-point estimate and associated confidence intervals.
- Incidence of toxicity of trebananib alone and in combination with anti-VEGF agent assessed using CTCAE version 4.0 [ Time Frame: Up to 8 weeks ]Toxicities (grade, type, cycle, and attribution) experienced will be listed for each patient and summarized using standard descriptive methods, such as point estimates and associated confidence intervals.
- Progression free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 8 weeks ]Kaplan-Meier plots will be used to display the PFS in each arm.
- Tolerance of trebananib alone and in combination with anti-VEGF agent assessed using CTCAE version 4.0 [ Time Frame: Up to 8 weeks ]
- Changes in circulating angiogenic factors [ Time Frame: Baseline to up to 8 weeks ]Analyzed as continuous variables (most likely after transformation). The gene expression results from the pretreatment tumor biopsies are expressed as ratios between that of the gene of interest and the internal reference gene beta-actin and can be analyzed as continuous variables - generally after log transformation.
- Expression of angiogenic genes in RCC tumors [ Time Frame: Up to 8 weeks ]The mean levels and patient-to-patient variability based on the two sets of specimens (archival and research biopsy) will be compared. The Spearman correlation coefficient and associated 95% confidence interval will be calculated.
- Pre-treatment tumor gene expression levels [ Time Frame: Baseline ]
- SNPs in angiogenic genes [ Time Frame: Up to 8 weeks ]
|Actual Study Start Date:||August 1, 2012|
|Estimated Primary Completion Date:||December 31, 2017 (Final data collection date for primary outcome measure)|
Experimental: Arm I (trebananib monotherapy)
Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
Correlative studiesBiological: Trebananib
Experimental: Arm II (trebananib and anti-VEGF therapy)
Patients receive trebananib as in Arm I and either bevacizumab IV over 30-90 minutes on days 1, 15, and 29; pazopanib hydrochloride PO QD on days 1-42; sorafenib tosylate PO BID on days 1-42; or sunitinib malate PO QD on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Given IVOther: Laboratory Biomarker Analysis
Correlative studiesDrug: Pazopanib Hydrochloride
Given POOther: Pharmacological Study
Correlative studiesDrug: Sorafenib Tosylate
Given PODrug: Sunitinib Malate
Given POBiological: Trebananib
I. To evaluate the overall response rate (complete response [CR] + partial response [PR]) of trebananib (AMG 386) alone and in combination with continuation of previously administered bevacizumab, pazopanib hydrochloride (pazopanib), sorafenib tosylate (sorafenib), or sunitinib malate (sunitinib) in advanced renal cell carcinoma.
I. To evaluate progression free survival in each arm. II. To evaluate the tolerance and toxicity of AMG 386 alone and in combination with continuation of the prior VEGF targeted agent.
I. To evaluate the association between pretreatment tumor gene expression levels and response to AMG 386 in combination with continuation of the prior VEGF targeted agent.
II. To evaluate the association between single nucleotide polymorphisms (SNPs) in angiogenic genes and response to AMG 386 in combination with continuation of the prior VEGF targeted agent.
III. To compare changes in circulating angiogenic factors in patients treated with AMG 386 monotherapy to those treated with AMG 386 in combination with VEGF-targeted therapy.
IV. To compare expression of angiogenic genes from archival tumor specimens to the expression in biopsy specimens obtained after progression on anti-VEGF therapy.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive trebananib intravenously (IV) over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive trebananib as in Arm I and either bevacizumab IV over 30-90 minutes on days 1, 15, and 29; pazopanib hydrochloride orally (PO) once daily (QD) on days 1-42; sorafenib tosylate PO twice daily (BID) on days 1-42; or sunitinib malate PO QD on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4-8 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01664182
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|City of Hope South Pasadena|
|South Pasadena, California, United States, 91030|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Metro Minnesota Community Oncology Research Consortium|
|Saint Louis Park, Minnesota, United States, 55416|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Virginia|
|VCU Massey Cancer Center at Hanover Medical Park|
|Mechanicsville, Virginia, United States, 23116|
|Principal Investigator:||Thomas Semrad||City of Hope Comprehensive Cancer Center|