Trebananib With or Without Bevacizumab, Pazopanib Hydrochloride, Sorafenib Tosylate, or Sunitinib Malate in Treating Patients With Advanced Kidney Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01664182
First received: August 10, 2012
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

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. 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.


Condition Intervention Phase
Recurrent Renal Cell Cancer
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Biological: trebananib
Biological: bevacizumab
Drug: pazopanib hydrochloride
Drug: sorafenib tosylate
Drug: sunitinib malate
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]
  • 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.


Other Outcome Measures:
  • 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 ]
  • 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.


Estimated Enrollment: 78
Study Start Date: August 2012
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: trebananib
Given IV
Other Names:
  • AMG 386
  • AMG386
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
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.
Biological: trebananib
Given IV
Other Names:
  • AMG 386
  • AMG386
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: pazopanib hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient
Drug: sorafenib tosylate
Given PO
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: sunitinib malate
Given PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

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.

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 vascular endothelial growth factor (VEGF) targeted agent.

TERTIARY 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. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed renal cell carcinoma except medullary or collecting duct subtypes; sarcomatoid differentiation will be allowed
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Patients must have documented radiologic or clinical progressive disease following at least one prior anti-VEGF regimen administered either as a single agent or in combination with other agents for at least 8 weeks; the prior anti-VEGF treatment regimen must have included bevacizumab, pazopanib, sorafenib or sunitinib administered not more than 12 weeks before study entry; Note: enrollment not more than 8 weeks after the last dose of anti-VEGF therapy is encouraged; nevertheless, intercurrent therapy with an mammalian target of rapamycin (mTOR) inhibitor (everolimus or temsirolimus) will be allowed if progression on that treatment is observed within 12 weeks of the prior anti-VEGF therapy
  • Any number of prior regimens is allowed; prior investigational therapy is allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< institutional upper limits of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) =< upper limit of normal (ULN) per institutional laboratory range
  • International normalized ratio (INR) =< 1.5
  • Creatinine within normal institutional limits OR creatinine clearance > 40 mL/min per 24 hour (h) urine collection or calculated according to the Cockcroft-Gault formula
  • Urinary protein =< 100 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 h urine sample
  • Generally well-controlled blood pressure with systolic blood pressure =< 140 mmHg AND diastolic blood pressure =< 90 mmHg prior to enrollment; the use of anti-hypertensive medications to control hypertension is permitted
  • Patients must have a tumor site amenable to biopsy as determined by the treating investigator; any questions regarding suitability of a site for biopsy will be adjudicated by the principal investigator
  • Patients must be willing to consent to tumor biopsy for research purposes
  • Patients should have archival tumor tissue (either unstained slides or tumor blocks) available for retrieval
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 6 months after completion of AMG 386; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of AMG 386 and bevacizumab, pazopanib, sunitinib, or sorafenib administration
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Intolerance of prior treatment with bevacizumab, pazopanib, sorafenib, or sunitinib; Note: subjects who required a dose reduction of pazopanib, sorafenib, or sunitinib during prior therapy MAY be eligible if they tolerated the agent after dose level reduction (to a minimum of dose level -2 as defined in this protocol)
  • Central nervous system metastases unless: (1) metastases have been treated and have remained controlled for at least two weeks following treatment, AND (2) patient has no residual neurological dysfunction off corticosteroids for at least one week; a CT or MRI to evaluate for central nervous system (CNS) disease is required for symptomatic patients only
  • History of venous or arterial thromboembolism within 12 months prior to enrollment/randomization
  • History of clinically significant bleeding within 6 months of enrollment/randomization
  • Unresolved toxicities from prior systemic therapy that are Common Terminology Criteria in Adverse Events (CTCAE) version 3.0 or 4.0 >= grade 2 in severity except alopecia
  • Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
  • Clinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent
  • Major surgery within 28 days prior to enrollment or still recovering from prior surgery
  • Minor surgical procedures except placement of tunneled central venous access device within 3 days prior to enrollment
  • Non-healing wound, ulcer (including gastrointestinal), or fracture
  • Subject not consenting to the use of highly effective contraceptive precautions (e.g., double barrier method [i.e., condom plus diaphragm]) during the course of the study and for 6 months after administration of the last study medication
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AMG 386 or the anti-VEGF agent used in study
  • History of allergic reactions to bacterially-produced proteins
  • Patients who have had anti-VEGFR tyrosine kinase inhibitor within 1 week, mTOR inhibitor within 1 week or anti-VEGF antibody therapy within 3 weeks prior to entering the study; patients who have had other forms of chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who have not yet completed at least 21 days (30 days for prior monoclonal antibody therapy) since ending other investigational device or drug trials, or who are currently receiving other investigational treatments
  • Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4) are ineligible; caution is advised for patients requiring weak or moderate CYP450 3A4 inhibitors or inducers; specifically prohibited medicines include indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort, and troglitazone
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding must be discontinued if the mother is treated with AMG 386
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Inability to take oral medications on a continuous basis; patients who are to take pazopanib, sorafenib, or sunitinib and are unable to swallow pills whole are ineligible (the pills cannot be crushed or broken)
  • Any condition which in the investigator's opinion makes the subject unsuitable for study participation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01664182

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Przemyslaw W. Twardowski    626-256-4673ext62307    ptwardowski@coh.org   
Principal Investigator: Przemyslaw W. Twardowski         
University of Southern California/Norris Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: David I. Quinn    323-865-3956    diquinn@usc.edu   
Principal Investigator: David I. Quinn         
University of California at Davis Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Thomas J. Semrad    916-734-3771    thomas.semrad@ucdmc.ucdavis.edu   
Principal Investigator: Thomas J. Semrad         
City of Hope South Pasadena Recruiting
South Pasadena, California, United States, 91030
Contact: Stephen C. Koehler    626-396-2900    skoehler@cohmg.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    vaishamu@karmanos.org   
Principal Investigator: Ulka N. Vaishampayan         
United States, Pennsylvania
Penn State Milton S Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Chandra P. Belani    717-531-1078    cbelani@psu.edu   
Principal Investigator: Chandra P. Belani         
University of Pittsburgh Cancer Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Leonard J. Appleman    412-648-6507    applemanlj@upmc.edu   
Principal Investigator: Leonard J. Appleman         
Sponsors and Collaborators
Investigators
Principal Investigator: Thomas Semrad Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01664182     History of Changes
Other Study ID Numbers: NCI-2012-01289, NCI-2012-01289, CDR0000738785, PHII-122, 9048, N01CM00038, P30CA033572
Study First Received: August 10, 2012
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antibodies
Antibodies, Monoclonal
Endothelial Growth Factors
Bevacizumab
Niacinamide
Sunitinib
Trenananib
Sorafenib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Growth Substances
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 18, 2014