Trebananib With or Without Bevacizumab, Pazopanib Hydrochloride, Sorafenib Tosylate, or Sunitinib Malate in Treating Patients With Advanced Kidney Cancer
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. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor. Bevacizumab, 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.
Recurrent Renal Cell Carcinoma
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Other: Laboratory Biomarker Analysis
Drug: Pazopanib Hydrochloride
Other: Pharmacological Study
Drug: Sorafenib Tosylate
Drug: Sunitinib Malate
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]
- Changes in circulating angiogenic factors [ Time Frame: Baseline to up to 8 weeks ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- SNPs in angiogenic genes [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||August 2012|
|Estimated Primary Completion Date:||May 2016 (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.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Pazopanib Hydrochloride
Other Names:Other: Pharmacological Study
Correlative studiesDrug: Sorafenib Tosylate
Other Names:Drug: Sunitinib Malate
Other Names:Biological: Trebananib
I. To evaluate the overall response rate (complete response [CR] + partial response [PR]) of AMG 386 (trebananib) alone and in combination with continuation of previously administered bevacizumab, pazopanib (pazopanib hydrochloride), sorafenib (sorafenib tosylate), or sunitinib (sunitinib malate) 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 vascular endothelial growth factor (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||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Przemyslaw W. Twardowski 626-256-4673 ext 62307 firstname.lastname@example.org|
|Principal Investigator: Przemyslaw W. Twardowski|
|USC / Norris Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90033|
|Contact: David I. Quinn 323-865-3956 email@example.com|
|Principal Investigator: David I. Quinn|
|University of California Davis Comprehensive Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Thomas J. Semrad 916-734-3771 firstname.lastname@example.org|
|Principal Investigator: Thomas J. Semrad|
|City of Hope South Pasadena||Recruiting|
|South Pasadena, California, United States, 91030|
|Contact: Stephen C. Koehler 626-396-2900 email@example.com|
|Principal Investigator: Stephen C. Koehler|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Ulka N. Vaishampayan 313-576-8715 firstname.lastname@example.org|
|Principal Investigator: Ulka N. Vaishampayan|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Brian A. Costello 507-284-2511 email@example.com|
|Principal Investigator: Brian A. Costello|
|Saint Louis Park, Minnesota, United States, 55416|
|Contact: Patrick J. Flynn 952-993-1550 MMCCOP@parknicollet.com|
|Principal Investigator: Patrick J. Flynn|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey||Recruiting|
|New Brunswick, New Jersey, United States, 08903|
|Contact: Mark N. Stein 732-235-6031 firstname.lastname@example.org|
|Principal Investigator: Mark N. Stein|
|United States, North Carolina|
|University of North Carolina at Chapel Hill||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Kimryn Rathmell 919-966-4432 email@example.com|
|Principal Investigator: Kimryn Rathmell|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center||Recruiting|
|Hershey, Pennsylvania, United States, 17033-0850|
|Contact: Chandra P. Belani 717-531-1078 firstname.lastname@example.org|
|Principal Investigator: Chandra P. Belani|
|University of Pittsburgh Cancer Institute||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: Leonard J. Appleman 412-648-6507 email@example.com|
|Principal Investigator: Leonard J. Appleman|
|United States, Virginia|
|VCU Massey Cancer Center at Hanover Medical Park||Recruiting|
|Mechanicsville, Virginia, United States, 23116|
|Contact: Craig Swainey 804-828-9723 firstname.lastname@example.org|
|Principal Investigator: Craig Swainey|
|National University Hospital Singapore||Recruiting|
|Singapore, Singapore, 119074|
|Contact: Alvin S. Wong 65-6772-2527 email@example.com|
|Principal Investigator: Alvin S. Wong|
|Principal Investigator:||Thomas Semrad||Beckman Research Institute|