This randomized phase II trial studies how well trebananib with or without bevacizumab, pazopanib hydrochloride, sorafenib tosylate, or sunitinib malate works in treating patients with kidney cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor. Immunotherapy with monoclonal, such as bevacizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pazopanib hydrochloride, sorafenib tosylate, and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. It is not yet known whether giving trebananib with or without bevacizumab, pazopanib hydrochloride, sorafenib tosylate, or sunitinib malate is more effective in treating kidney cancer.
PRIMARY OBJECTIVE: 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. SECONDARY OBJECTIVES: 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. CORRELATIVE OBJECTIVES: 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. Cycles 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. Cycles 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Given IV
Given PO
Given PO
Given PO
Given IV
City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States
...and 2 more locations
Observed Response Rate
Defined as the total number of efficacy-evaluable patients who achieve a complete or partial response by RECIST version 1.1 criteria, assessed by MRI: Complete Response (CR), Disappearance of all target lesions: any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Best response will be listed for each patient and summarized using standard descriptive methods-point estimate and associated confidence intervals.
Time frame: Up to 8 weeks
Tumor Response
Tumor Response Classification
Time frame: at 8 weeks
Progression Free Survival (PFS)
Time to reach Kaplan-Meier median survival (outcome being death or progression) (95% Confidence Interval) is reported. Progressive Disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered a progression.)
Time frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 8 weeks
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs
Adverse events were graded using CTCAE version 5.0. Grades 3, 4, 5 (on a scale of 1 to 5, 5 being the worst grade - death) toxicities related ('Possibly', 'Probably', or 'Definitely') to the treatment drugs (AMG 386 alone or in combination with prior VEGF targeted agent).
Time frame: 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks
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