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CompletedNCT01664182Updated Jun 7, 2022Results posted

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

A Phase 2 interventional study of Bevacizumab and Pazopanib Hydrochloride in Advanced Renal Cell Carcinoma, Advanced Sarcomatoid Renal Cell Carcinoma and Stage III Renal Cell Cancer AJCC v7, sponsored by National Cancer Institute (NCI). Completed at 12 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-06-07.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
41
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Advanced Renal Cell Carcinoma
  • Advanced Sarcomatoid Renal Cell Carcinoma
  • Stage III Renal Cell Cancer AJCC v7
  • Stage IV Renal Cell Cancer AJCC v7
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 41 is close to the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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 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
  • The effects of AMG 386 are known to be detrimental to fetal development; for this reason and because inhibitors of angiogenesis as well as other therapeutic agents used in this trial are known to be teratogenic, 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

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 because AMG 386, bevacizumab, pazopanib, sorafenib, and sunitinib are inhibitors of angiogenesis with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AMG 386, breastfeeding must be discontinued if the mother is treated with AMG 386
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pazopanib, sorafenib, or sunitinib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; 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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
41 participants (actual)

Study arms

  • Experimental
    Arm I (trebananib monotherapy)

    Patients receive trebananib 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.

    Biological: 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. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.

    Biological: Bevacizumab · Drug: Pazopanib Hydrochloride · Drug: Sorafenib Tosylate · Drug: Sunitinib Malate · Biological: Trebananib

Interventions

  • BiologicalBevacizumab

    Given IV

    Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501

  • DrugPazopanib Hydrochloride

    Given PO

    Also known as: GW786034B, Votrient

  • DrugSorafenib Tosylate

    Given PO

    Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

  • DrugSunitinib Malate

    Given PO

    Also known as: SU011248, SU11248, sunitinib, Sutent

  • BiologicalTrebananib

    Given IV

    Also known as: AMG 386, AMG386, Angiopoietin 1/2-Neutralizing Peptibody AMG 386

06

What researchers measure

Primary outcomes

  1. 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

  2. Tumor Response

    Tumor Response Classification

    Time frame: at 8 weeks

Secondary outcomes

  1. 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

  2. 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

Other outcomes

  1. Changes in Circulating Angiogenic Factors

    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.

    Time frame: Baseline to up to 8 weeks

07

Results

Posted Jun 7, 2022

Participant flow

Participant flow — Overall Study
MilestoneArm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)
Started1922
Completed1718
Not completed24

Outcome measures

PrimaryObserved 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
Reported as:
Number · percentage of patients responding
Observed Response Rate
percentage of patients respondingArm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)
Observed Response Rate0 (0 to 20)11 (1 to 35)
PrimaryTumor Response

Tumor Response Classification

Time frame:
at 8 weeks
Reported as:
Count of participants · Participants
Tumor Response
ParticipantsArm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)
Partial Response02
Stable Disease58
Progressive Disease116
Not Evaluable12
SecondaryProgression 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
Reported as:
Median · months
Progression Free Survival (PFS)
monthsArm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)
Progression Free Survival (PFS)2.7 (2.3 to 4.7)5.2 (2.7 to 10.8)
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs
ParticipantsArm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)
SAE Cardiac disorders: Cardiac arrest01
SAE Metabolism and nutrition disorders: Hypokalemia10
SAE Respiratory, thoracic and mediastinal disorders: Dyspnea11
SAE Respiratory, thoracic and mediastinal disorders: Pleural effusion10
Blood and lymphatic system disorders: Anemia01
General disorders and administrative site conditions: Fatigue13
Investigations: Lymphocyte count decreased01
Investigations: Weight gain01
Metabolism and nutrition disorders: Acidosis01
Metabolism and nutrition disorders: Hyperglycemia10
Metabolism and nutrition disorders: Hyponatremia01
Musculoskeletal and connective tissue disorders: Back pain11
Vascular disorders: Hypertension33
Other pre-specifiedChanges in Circulating Angiogenic Factors

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.

Time frame:
Baseline to up to 8 weeks
Reported as:
Median · pg/ml
Changes in Circulating Angiogenic Factors
pg/mlArm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)
Angiopoietin--2 at baseline3909 (3246 to 4863)3237 (2424 to 4813)
Angiopoietin--2 prior to cycle 2132156 (110775 to 160316)120956 (84474 to 131643)
Angiopoietin--2 prior to cycle 3125928 (114871 to 141528)96075 (84200 to 150486)
Tie--2 at baseline803 (510 to 1035)835 (650 to 1094)
Tie--2 prior to cycle 2783 (535 to 1041)671 (571 to 856)
Tie--2 prior to cycle 3912 (263 to 1232)753 (424 to 912)
VEGF--A at baseline27.3 (10.5 to 48.4)26.1 (19.6 to 38.0)
VEGF--A prior to cycle 221.3 (10.5 to 29.0)33.4 (13.6 to 48.2)
VEGF--A prior to cycle 320.7 (0.3 to 34.2)41.2 (26.1 to 56.7)
PIGF at baseline31.1 (26.1 to 35.2)30.7 (28.3 to 46.7)
PIGF prior to cycle 230.5 (21.8 to 36.0)33.6 (29.9 to 39.2)
PIGF prior to cycle 331.4 (30.5 to 34.3)31.5 (26.3 to 41.8)
VEGFR--3 at baseline873 (157 to 1073)489 (50 to 898)
VEGFR--3 prior to cycle 2722 (117 to 869)50 (50 to 321)
VEGFR--3 prior to cycle 3489 (362 to 954)50 (50 to 416)
VEGF--C at baseline255 (72 to 425)283 (251 to 380)
VEGF--C prior to cycle 2209 (67 to 340)311 (247 to 357)
VEGF--C prior to cycle 3230 (45 to 358)311 (154 to 503)
IL--8 at baseline0.1 (0.1 to 12.6)0.1 (0.1 to 4.0)
IL--8 prior to cycle 23.6 (0.1 to 17.5)5.9 (0.1 to 13.5)
IL--8 prior to cycle 32.5 (0.1 to 8.1)0.4 (0.1 to 17.3)
ICAM--1 at baseline161879 (103645 to 240620)243594 (185653 to 601003)
ICAM--1 prior to cycle 2193335 (117584 to 247434)239027 (160295 to 318968)
ICAM--1 prior to cycle 3262636 (221161 to 266594)200959 (150610 to 276615)
VCAM--1 at baseline965554 (738499 to 1421550)1307900 (982643 to 1946700)
VCAM--1 prior to cycle 21336300 (955663 to 1903550)1850000 (1327000 to 2555600)
VCAM--1 prior to cycle 3982488 (969237 to 1581000)1666200 (1351500 to 2091050)
FGF2 at baseline124 (105 to 136)120 (105 to 136)
FGF2 prior to cycle 2112 (89 to 131)110 (95 to 132)
FGF2 prior to cycle 3131 (104 to 136)120 (97 to 133)
PDGF -- AA at baseline351 (237 to 788)478 (112 to 647)
PDGF -- AA prior to cycle 2291 (190 to 394)262 (213 to 829)
PDGF -- AA prior to cycle 3264 (119 to 710)173 (105 to 777)
Statistical analysis
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.86 (No adjustment for multiple comparisons. A-priori threshold for statistical significance is 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.76 (Angiopoietin -- 2 prior to cycle 3.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.14 (No adjustment for multiple comparison. A-priori threshold for statistical significance is 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.069 (No adjustment for multiple comparisons. A-priori threshold for statistical significance is 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.19 (P-value is not adjusted for multiple comparisons. A-priori threshold for statistical significance is 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.046 (P-value is not adjusted for multiple comparisons. The a-priori threshold for statistical significance is 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.029 (Not adjusted for multiple comparisons. A-priori threshold for statistical significance is 0.05)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.20 (P-value is not adjusted for multiple comparisons. A priori threshold for statistical significance is 0.05)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.11 (The p-value was not adjusted for multiple comparisons. The a-priori threshold for statistical significance is 0.05)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.068 (P-value was not adjusted for multiple comparisons. The a-priori threshold for statistical significance was 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.61 (The p-value was not adjusted for multiple comparisons. The a-priori threshold for statistical significance was 0.05)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.27 (Two sided hypothesis. Wilcoxon rank-sum test comparing the two arms in terms of the ratio of the post-treatment levels divided by the baseline.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.61 (The p-value was not adjusted for multiple comparisons. The a-priori threshold for statistical significance was 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.49 (The p-value was not adjusted for multiple comparisons, and the a-priori threshold for statistical significance was 0.05)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.82 (The p-value was not adjusted for multiple comparisons. The a-priori threshold for statistical significance was 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.069 (The p-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.34 (The p-value was not adjusted for multiple comparisons. The a priori threshold for statistical significance was 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.046 (The p-value was not adjusted for multiple comparisons. The a priori threshold for statistical significance was set to 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.11 (The p-value was not adjusted for multiple comparisons. The a priori threshold for statistical significance was set to 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.23 (The p-value was adjusted for multiple comparisons. The a prior threshold for statistical significance was set to 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.37 (The p-value was not adjusted for multiple comparisons. The a priori threshold for statistical significance was set to 0.05.)
  • Arm I (Trebananib Monotherapy) vs Arm II (Trebananib and Anti-VEGF Therapy) · Wilcoxon (Mann-Whitney) · p = 0.35 (The p-value was not adjusted for multiple comparisons. The a priori threshold for statistical significance was set to 0.05.)

Adverse events

Collected over 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm I (Trebananib Monotherapy)0/17 (0%)10/17 (58.8%)16/17 (94.1%)
Arm II (Trebananib and Anti-VEGF Therapy)2/18 (11.1%)18/18 (100%)18/18 (100%)
Most frequent serious events
Showing 10 of 25
Most frequent serious events
EventArm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)
DyspneaRespiratory, thoracic and mediastinal disorders1/173/18
Myocardial infarctionCardiac disorders0/172/18
Acute kidney injuryRenal and urinary disorders0/172/18
NauseaGastrointestinal disorders1/171/18
Urinary tract infectionInfections and infestations1/170/18
UrosepsisInfections and infestations1/170/18
Lymphocyte count decreasedInvestigations1/171/18
HyperglycemiaMetabolism and nutrition disorders1/170/18
HypokalemiaMetabolism and nutrition disorders1/170/18
Back painMusculoskeletal and connective tissue disorders1/170/18
Most frequent other events
Showing 10 of 163
Most frequent other events
EventArm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)
HypertensionVascular disorders5/1711/18
FatigueGeneral disorders9/1710/18
Creatinine increasedInvestigations4/1710/18
NauseaGastrointestinal disorders7/178/18
DyspneaRespiratory, thoracic and mediastinal disorders7/173/18
HyponatremiaMetabolism and nutrition disorders6/177/18
ProteinuriaRenal and urinary disorders4/177/18
AnemiaBlood and lymphatic system disorders5/176/18
Weight gainInvestigations2/176/18
HypoalbuminemiaMetabolism and nutrition disorders4/176/18

Baseline characteristics

Age, Continuous
Age, Continuous(years)Arm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)Total
Median64 (49 to 76)59 (46 to 74)60 (46 to 76)
Sex: Female, Male
Sex: Female, Male(Participants)Arm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)Total
Female448
Male131427
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Arm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)Total
American Indian/Alaska Native202
Asian/Pacific Islander011
Black213
Hispanic448
White91221
Region of Enrollment
Region of Enrollment(participants)Arm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)Total
United States171835
ECOG Performance Score
ECOG Performance Score(Participants)Arm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)Total
0121123
15712
Prior Anti-VEGF Agent
Prior Anti-VEGF Agent(Participants)Arm I (Trebananib Monotherapy)Arm II (Trebananib and Anti-VEGF Therapy)Total
Bevacizumab51015
Pazopanib6511
Sorafenib224
Sunitinib415
08

Study locations

12 sites
  • City of Hope Comprehensive Cancer Center
    Duarte, California 91010, United States
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California 95817, United States
  • City of Hope South Pasadena
    South Pasadena, California 91030, United States
  • Wayne State University/Karmanos Cancer Institute
    Detroit, Michigan 48201, United States
  • Mayo Clinic in Rochester
    Rochester, Minnesota 55905, United States
  • Metro Minnesota Community Oncology Research Consortium
    Saint Louis Park, Minnesota 55416, United States
  • Rutgers Cancer Institute of New Jersey
    New Brunswick, New Jersey 08903, United States
  • UNC Lineberger Comprehensive Cancer Center
    Chapel Hill, North Carolina 27599, United States
  • Penn State Milton S Hershey Medical Center
    Hershey, Pennsylvania 17033-0850, United States
  • University of Pittsburgh Cancer Institute (UPCI)
    Pittsburgh, Pennsylvania 15232, United States
  • VCU Massey Cancer Center at Hanover Medical Park
    Mechanicsville, Virginia 23116, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Aug 26, 2020

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 7, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01664182
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Aug 14, 2012
Start date
Aug 1, 2012
Primary completion
Dec 7, 2020
Completion
Dec 7, 2020
Results posted
Jun 7, 2022
Last update
Jun 7, 2022

Study contacts

Thomas J Semrad
principal investigator · City of Hope Comprehensive Cancer Center
View the source record on ClinicalTrials.gov ↗

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