Trial record 3 of 273 for:    Open Studies | "Carcinoma, Renal Cell"

Bevacizumab With or Without Monoclonal Antibody Therapy in Treating Patients With Metastatic Kidney Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01727089
First received: November 12, 2012
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

This randomized phase II trial studies how well bevacizumab with or without monoclonal antibody therapy works in treating patients with metastatic kidney cancer. Monoclonal antibodies, such as bevacizumab and anti-endoglin monoclonal antibody TRC105, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.


Condition Intervention Phase
Clear Cell Renal Cell Carcinoma
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Type 1 Papillary Renal Cell Carcinoma
Type 2 Papillary Renal Cell Carcinoma
Biological: bevacizumab
Biological: anti-endoglin monoclonal antibody TRC105
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Bevacizumab Alone or in Combination With TRC 105 for Advanced Renal Cell Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: The duration of time from start of treatment to time of progression or death, assessed at 12 weeks ] [ Designated as safety issue: No ]
    Planning is based on the supposition of 12-week PFS of 61% on the control arm and 78% on the combination arm.

  • PFS [ Time Frame: The duration of time from start of treatment to time of progression or death, assessed at 24 weeks ] [ Designated as safety issue: No ]
    The corresponding hypothesized PFS at 24 weeks would be 37% on the single-agent arm and 60% on the combination arm.


Secondary Outcome Measures:
  • Response rate assessed by RECIST [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
  • Incidence of adverse events (AE) and toxicity of study treatment [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • Change in CD105 expression [ Time Frame: Baseline to week 13 ] [ Designated as safety issue: No ]
    Generalized linear models for ordered categorical data will be used to address the treatment and staining interaction using the full dataset.

  • Change in TGFbeta-R2 expression [ Time Frame: Baseline to week 13 ] [ Designated as safety issue: No ]
  • Change in TGFBR1 expression [ Time Frame: Baseline to week 13 ] [ Designated as safety issue: No ]
  • Change in activin A receptor type II-like 1 expression [ Time Frame: Baseline to week 13 ] [ Designated as safety issue: No ]

Estimated Enrollment: 88
Study Start Date: November 2012
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: laboratory biomarker analysis
Correlative studies
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.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Biological: anti-endoglin monoclonal antibody TRC105
Given IV
Other Name: TRC105
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed 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. A primary goal of tissue analysis will be to generate preliminary data to correlate levels of CD105, TGFBR2, ACVRL1 and TGFBR1 in tissue with response to bevacizumab in combination with anti-endoglin monoclonal antibody TRC105 compared to bevacizumab alone.

III. 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.

IV. 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.

V. 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 for 4 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 due to the risk of bleeding; 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] > 160mmHg 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01727089

  Show 27 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Tanya Dorff Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01727089     History of Changes
Other Study ID Numbers: NCI-2012-02206, NCI-2012-02206, PHII-121, 9144, N01CM00071, P30CA033572, N01CM00039, N01CM00099, N01CM00038
Study First Received: November 12, 2012
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Bevacizumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014