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Clear Cell Renal Cell CarcinomaPhase 2NCT01727089

Bevacizumab With or Without TRC105 in Treating Patients With Metastatic Kidney Cancer

A Phase 2 study testing Anti-Endoglin Chimeric Monoclonal Antibody TRC105, Bevacizumab and Laboratory Biomarker Analysis in people with Clear Cell Renal Cell Carcinoma and Recurrent Renal Cell Carcinoma, run by National Cancer Institute (NCI) at 30 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anti-Endoglin Chimeric Monoclonal Antibody TRC105, Bevacizumab and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
30 sitesin 3 countries
Study dates
1 Nov 2012to 8 Aug 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • 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
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  • Patients on full-dose anticoagulation will be excluded; antiplatelet therapy will not be exclusionary
  • 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
  • Patients with clinically significant cardiovascular disease are excluded:
  • Inadequately controlled hypertension (HTN) (systolic blood pressure [SBP] > 160 mmHg and/or diastolic blood pressure [DBP] > 90 mmHg despite antihypertensive medication)
  • History of cerebrovascular accident (CVA) within 6 months
  • Myocardial infarction or unstable angina within 6 months
  • New York Heart Association grade II or greater congestive heart failure
  • Serious and inadequately controlled cardiac arrhythmia
  • Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection)
  • Clinically significant peripheral vascular disease
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements will be excluded

Trial locations and contacts

30 sites in 3 countries.

30 sites in 3 countries

United States28 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • University of Colorado Cancer Center - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • University of Colorado

    Denver, Colorado, 80217-3364

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard

    Fort Wayne, Indiana, 46804

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • NorthShore University HealthSystem-Glenbrook Hospital

    Glenview, Illinois, 60026

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

  • City of Hope South Pasadena

    South Pasadena, California, 91030

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

Australia1 site

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

Other trials in Australia

Taiwan1 site

  • National Taiwan University Hospital

    Taipei, 100

Other trials in Taiwan

About this study

Official title: A Phase II Study of Bevacizumab Alone or in Combination With TRC105 for Advanced Renal Cell Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare the progression-free survival at 12 and 24 weeks for bevacizumab alone or in combination with TRC105 (anti-endoglin monoclonal antibody TRC105).

SECONDARY OBJECTIVES:

  1. Toxicity and Response Evaluation Criteria in Solid Tumors (RECIST) response rate for the combination compared to single agent bevacizumab.

TERTIARY OBJECTIVES:

  1. To evaluate tumor tissue expression of endoglin (CD105), transforming growth factor, beta receptor II (TGFBR2), activin A receptor type II-like 1 (ACVRL1) and transforming growth factor, beta receptor 1 (TGFBR1) kinase from pre- and post-treatment tissue samples in order to determine whether CD105 and stem cell activation occurs after exposure to anti-vascular endothelial growth factor (VEGF) therapy as predicted by laboratory models, and whether exposure to anti-endoglin monoclonal antibody TRC105 affects these changes.

II. To compare the soluble CD105 levels at baseline and after treatment between the group receiving bevacizumab alone and the group receiving bevacizumab in combination with anti-endoglin monoclonal antibody TRC105.

III. To compare TGFBR2 levels at baseline and after treatment between the group receiving bevacizumab alone and the group receiving bevacizumab in combination with anti-endoglin monoclonal antibody TRC105.

IV. To evaluate whether circulating tumor cells (CTCs) can be detected in this patient population using parylene membrane filter technology, and whether changes in CTC counts and CD105 expression on CTCs during therapy correspond to imaging and clinical response.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.

ARM II: 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.

In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for 4 weeks.

Being tested
Anti-Endoglin Chimeric Monoclonal Antibody TRC105, Bevacizumab, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-Endoglin Chimeric Monoclonal Antibody TRC105Biological

    Also called TRC105

    Given IV

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01727089
Study groupRoleWhat they receive
Arm I (bevacizumab)Active comparatorPatients 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.
Receives: Biological: Bevacizumab; Other: Laboratory Biomarker Analysis
Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)ExperimentalPatients 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.
Receives: Biological: Anti-Endoglin Chimeric Monoclonal Antibody TRC105; Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

Secondary outcomes (2)

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

    The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be utilized for AE reporting.

    Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

    Grade 2 - Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL).

    Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.

    Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related adverse event.

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

  2. Number of Participants With Overall Response

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Nov 2012 (estimated)
  2. Study start1 Nov 2012
  3. Primary completion8 Aug 2017
  4. Study completion8 Aug 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01727089
Sponsor's protocol ID
NCI-2012-02206
Other IDs
NCI-2012-02206, PHII-121, PhII-121, 9144, N01CM00038, N01CM00039, N01CM00071, N01CM00099
Status last verified
Jul 2018
First submitted
12 Nov 2012
Last updated
28 Aug 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anti-Endoglin Chimeric Monoclonal Antibody TRC105, Bevacizumab and Laboratory Biomarker Analysis in people with Clear Cell Renal Cell Carcinoma and Recurrent Renal Cell Carcinoma, run by National Cancer Institute (NCI) at 30 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in United States, Australia, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival at 24 Weeks (time frame: The duration of time from start of treatment to time of progression or death, assessed at 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01727089.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2018.

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