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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01727089




Registration number
NCT01727089
Ethics application status
Date submitted
12/11/2012
Date registered
15/11/2012
Date last updated
28/08/2018

Titles & IDs
Public title
Bevacizumab With or Without TRC105 in Treating Patients With Metastatic Kidney Cancer
Scientific title
A Phase II Study of Bevacizumab Alone or in Combination With TRC105 for Advanced Renal Cell Cancer
Secondary ID [1] 0 0
NCI-2012-02206
Secondary ID [2] 0 0
NCI-2012-02206
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Clear Cell Renal Cell Carcinoma 0 0
Recurrent Renal Cell Carcinoma 0 0
Stage IV Renal Cell Cancer 0 0
Type 1 Papillary Renal Cell Carcinoma 0 0
Type 2 Papillary Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Anti-Endoglin Chimeric Monoclonal Antibody TRC105
Treatment: Other - Bevacizumab
Other interventions - Laboratory Biomarker Analysis
Other interventions - Pharmacological Study

Active comparator: Arm I (bevacizumab) - 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.

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


Treatment: Other: Anti-Endoglin Chimeric Monoclonal Antibody TRC105
Given IV

Treatment: Other: Bevacizumab
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Other interventions: Pharmacological Study
Correlative studies
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival at 24 Weeks
Timepoint [1] 0 0
The duration of time from start of treatment to time of progression or death, assessed at 24 weeks
Primary outcome [2] 0 0
Progression-free Survival at 12 Weeks
Timepoint [2] 0 0
The duration of time from start of treatment to time of progression or death, assessed at 12 weeks
Secondary outcome [1] 0 0
Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment
Timepoint [1] 0 0
From time of treatment initiation until 30 days post treatment, assessed every 4 weeks.
Secondary outcome [2] 0 0
Number of Participants With Overall Response
Timepoint [2] 0 0
From time of treatment initiation until conclusion of treatment, assessed every 12 weeks.

Eligibility
Key inclusion criteria
* 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
* Ability to understand and the willingness to sign a written informed consent document
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/08/2017
Sample size
Target
Accrual to date
Final
59
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
Taiwan
State/province [16] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT01727089
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tanya Dorff
Address 0 0
City of Hope Comprehensive Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01727089