Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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 October 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: November 21, 2014
Last verified: October 2014

August 10, 2012
November 21, 2014
August 2012
May 2015   (final data collection date for primary outcome measure)
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.
Overall tumor response rate (ORR) defined as the total number of efficacy-evaluable patients who achieve a complete or partial response by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria [ Time Frame: Up to 8 weeks post-treatment ] [ Designated as safety issue: No ]
Both arms will be evaluated separately using a Simon Optimum design. If trebananib is ineffective (alone or in the presence of an anti-VEGF agent), then we would expect to see no objective responses (by RECIST v1.1), while a 15% response rate would be taken as interesting enough to encourage future study.
Complete list of historical versions of study NCT01664182 on ClinicalTrials.gov Archive Site
  • 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.
  • Progression free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 8 weeks post-treatment ] [ Designated as safety issue: No ]
    Kaplan-Meier plots will be used to display the PFS in each arm.
  • Tolerance and toxicity of trebananib alone and in combination with anti-VEGF agent assessed using CTCAE version 4.0 [ Time Frame: Up to 8 weeks post-treatment ] [ 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.
  • 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.
Not Provided
 
Trebananib With or Without Bevacizumab, Pazopanib Hydrochloride, Sorafenib Tosylate, or Sunitinib Malate in Treating Patients With Advanced Kidney Cancer
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Renal Cell Carcinoma
  • Stage III Renal Cell Cancer
  • Stage IV Renal Cell Cancer
  • Biological: Trebananib
    Given IV
    Other Names:
    • AMG 386
    • Angiopoietin 1/2-Neutralizing Peptibody AMG 386
  • Biological: Bevacizumab
    Given IV
    Other Names:
    • Avastin
    • rhuMab-VEGF
  • Drug: Pazopanib Hydrochloride
    Given PO
    Other Names:
    • GW786034B
    • Votrient
  • Drug: Sorafenib Tosylate
    Given PO
    Other Names:
    • BAY 54-9085
    • Nexavar
    • SFN
  • Drug: Sunitinib Malate
    Given PO
    Other Names:
    • SU011248
    • SU11248
    • sunitinib
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacological Study
    Correlative studies
    Other Name: pharmacological studies
  • 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.
    Interventions:
    • Biological: Trebananib
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacological Study
  • 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.
    Interventions:
    • Biological: Trebananib
    • Biological: Bevacizumab
    • Drug: Pazopanib Hydrochloride
    • Drug: Sorafenib Tosylate
    • Drug: Sunitinib Malate
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacological Study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
78
Not Provided
May 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
United States
 
NCT01664182
NCI-2012-01289, NCI-2012-01289, CDR0000738785, PHII-122, 9048, N01CM00038, P30CA033572
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Thomas Semrad Beckman Research Institute
National Cancer Institute (NCI)
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP