NCT01727089

Brief Summary

This randomized phase II trial studies how well bevacizumab with or without anti-endoglin monoclonal antibody TRC105 (TRC105) works in treating patients with kidney cancer that has spread to other parts of the body (metastatic). Monoclonal antibodies, such as bevacizumab and anti-endoglin monoclonal antibody TRC105, may block tumor growth in different ways by targeting certain cells.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
59

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Nov 2012

Longer than P75 for phase_2

Geographic Reach
3 countries

30 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2012

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

November 12, 2012

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 15, 2012

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 8, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 8, 2017

Completed
11 months until next milestone

Results Posted

Study results publicly available

June 26, 2018

Completed
Last Updated

August 28, 2018

Status Verified

July 1, 2018

Enrollment Period

4.8 years

First QC Date

November 12, 2012

Results QC Date

April 24, 2018

Last Update Submit

July 30, 2018

Conditions

Outcome Measures

Primary Outcomes (2)

  • Progression-free Survival at 24 Weeks

    Progression-free survival 24 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    The duration of time from start of treatment to time of progression or death, assessed at 24 weeks

  • Progression-free Survival at 12 Weeks

    Progression-free survival 12 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    The duration of time from start of treatment to time of progression or death, assessed at 12 weeks

Secondary Outcomes (2)

  • Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment

    From time of treatment initiation until 30 days post treatment, assessed every 4 weeks.

  • Number of Participants With Overall Response

    From time of treatment initiation until conclusion of treatment, assessed every 12 weeks.

Study Arms (2)

Arm I (bevacizumab)

ACTIVE COMPARATOR

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Biological: BevacizumabOther: Laboratory Biomarker Analysis

Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)

EXPERIMENTAL

Patients receive bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Biological: Anti-Endoglin Chimeric Monoclonal Antibody TRC105Biological: BevacizumabOther: Laboratory Biomarker AnalysisOther: Pharmacological Study

Interventions

Given IV

Also known as: TRC105
Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)
BevacizumabBIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar FKB238, 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
Arm I (bevacizumab)Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)

Correlative studies

Arm I (bevacizumab)Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)

Correlative studies

Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have histologically or cytologically confirmed renal cancer; all histologic subtypes will be eligible
  • Patients must have metastatic disease which is measurable, 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) to \>= 20 mm in the long axis by chest x-ray, \>= 10 mm in the long axis by spiral computed tomography (CT), magnetic resonance imaging (MRI), calipers, or clinical exam, or \>= 15 mm in the short axis for lymph nodes
  • Patients must have received at least 1 prior systemic therapy for renal cancer but no more than 4 prior therapies; they must have documented intolerance to or progression despite at least 1 systemic therapy; therapy administered in the adjuvant setting counts toward the prior systemic therapy total; if adjuvant therapy is the patient's only prior therapy the disease must have recurred during treatment or within 3 months of discontinuation
  • Allowable prior therapies include VEGF tyrosine kinase inhibitor (TKIs), mammalian target of rapamycin (mTOR) inhibitors, and cytokine therapy (example: interleukin-2 \[IL2\])
  • At least 2 weeks must have elapsed from the last dose of the prior systemic therapy for biologics and 4 weeks for chemotherapy (6 weeks for nitrosoureas or mitomycin C); also note that at least 3 weeks should have elapsed since prior TKI administration
  • Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
  • Life expectancy of greater than 6 months
  • Leukocytes \>= 3,000/mcL
  • Absolute neutrophil count \>= 1,500/mcL
  • Platelets \>= 100,000/mcL
  • Total bilirubin =\< institutional upper limits or normal (except for Gilbert's)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal (except subjects with liver metastases, who can have AST/ALT =\< 5 x ULN)
  • Creatinine glomerular filtration rate (GFR) (calculated or measured) \> 50 mL/min
  • Hemoglobin \>= 9 g/dL
  • 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 and for the duration of study participation; 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 TRC105 or bevacizumab administration
  • +1 more criteria

You may not qualify if:

  • Patients who have had systemic biologic therapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events related to their prior therapy
  • Patients who have previously been treated with bevacizumab
  • Patients who have previously been treated with TRC105
  • Patients who are receiving any other investigational agents
  • Known central nervous system (CNS) disease except for treated brain metastasis; treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (MRI or CT) (stable dose of anticonvulsants are allowed); treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; gamma knife, linear accelerator \[LINAC\], or equivalent) or a combination as deemed appropriate by the treating physician; patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to TRC105 or bevacizumab
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unhealed wound, gastrointestinal fistula, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction, cerebrovascular accident
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother wishes to participate in the study
  • Patients with a history of bleeding diathesis or inherited coagulopathy are excluded; in addition, those with a history of deep vein thrombosis (DVT) or pulmonary embolus within 1 year and still requiring active anticoagulation will be excluded; those with a more remote history of DVT or pulmonary embolus may be eligible but the risk of recurrent thrombosis should be considered
  • Patients with history of hereditary hemorrhagic telangiectasis (HHT-1 and HHT-2)
  • Serious or non-healing wound, ulcer, or bone fracture OR history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1
  • Invasive procedures defined as follows:
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day 1 therapy
  • Anticipation of need for major surgical procedures during the course of the study
  • Core biopsy within 7 days prior to day 1 therapy
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (30)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

University of Colorado

Denver, Colorado, 80217-3364, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

NorthShore University HealthSystem-Glenbrook Hospital

Glenview, Illinois, 60026, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard

Fort Wayne, Indiana, 46804, United States

Location

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, 46845, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

carotuximabBevacizumabImmunoglobulin GDisulfides

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsImmunoglobulin IsotypesSulfidesAnionsIonsElectrolytesInorganic ChemicalsHydrogen SulfideSulfur CompoundsOrganic Chemicals

Results Point of Contact

Title
Jeff Longmate, Ph.D.
Organization
City of Hope

Study Officials

  • Tanya Dorff

    City of Hope Comprehensive Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 12, 2012

First Posted

November 15, 2012

Study Start

November 1, 2012

Primary Completion

August 8, 2017

Study Completion

August 8, 2017

Last Updated

August 28, 2018

Results First Posted

June 26, 2018

Record last verified: 2018-07

Locations