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

Clear Cell Renal Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01727089
• Other study ID #: NCI-2012-02206
• Secondary ID: NCI-2012-02206PH
• Status: Completed
• Phase: Phase 2
• Start date: November 1, 2012
• Est. completion date: August 8, 2017

Study information

• Verified date: July 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). Monoclonal antibodies, such as bevacizumab and anti-endoglin monoclonal antibody TRC105, may block tumor growth in different ways by targeting certain cells.

Description:

PRIMARY OBJECTIVES:

I. 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:

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

TERTIARY OBJECTIVES:

I. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: August 8, 2017
• Est. primary completion date: August 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma
• Recurrent Renal Cell Carcinoma
• Stage IV Renal Cell Cancer
• Type 1 Papillary Renal Cell Carcinoma
• Type 2 Papillary Renal Cell Carcinoma

Intervention

Biological:
• Anti-Endoglin Chimeric Monoclonal Antibody TRC105
Given IV
• Bevacizumab
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacological Study
Correlative studies

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Taiwan	National Taiwan University Hospital	Taipei
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	University of Colorado	Denver	Colorado
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard	Fort Wayne	Indiana
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	M D Anderson Cancer Center	Houston	Texas
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	City of Hope South Pasadena	South Pasadena	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.	From time of treatment initiation until 30 days post treatment, assessed every 4 weeks.
Secondary	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	From time of treatment initiation until conclusion of treatment, assessed every 12 weeks.