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Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma

This study is currently recruiting participants.
Verified June 2017 by University of Texas Southwestern Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02781506
First Posted: May 24, 2016
Last Update Posted: June 23, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center
  Purpose
Nivolumab (brand name Opdivo): IV, 3 mg/kg q2 weeks, until disease progression or unacceptable toxicity; SABR, dose variable, in 1-3 fractions.

Condition Intervention Phase
Metastatic Clear Cell Renal Cell Carcinoma Drug: Nivolumab Radiation: SAbR Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma (mRCC)

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Response Rate (RR) [ Time Frame: 5 years ]
    The primary objective of the randomized phase II trial will be to increase the RR of treatment with Nivolumab by the concurrent administration of SAbR. The assessment of RR will be based on the evaluation of irRECIST criteria and radiated lesions will be excluded from target lesions.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: 5 years ]
    To evaluate and compare the overall survival (OS), which is defined as the time between date of registration and the date of death due to any cause, between the Nivolumab alone and the combination therapy arms

  • Progression free survival [ Time Frame: 5 years ]
    To evaluate and compare progression free survival (PFS), which is defined as the time between date of registration and the first date of documented disease progression or date of death due to any cause, between the Nivolumab alone and the combination therapy arms

  • Complete response rate [ Time Frame: 5 years ]
    To evaluate and compare complete response rate in each arm, which is defined as the percentage of patients who show complete response as per ir-RECIST criteria

  • Time to progression [ Time Frame: 5 years ]
    To evaluate and compare time to progression (TTP), which is defined as time between date of registration and date of documented progression, between the experimental and control arms.

  • Median response duration [ Time Frame: 5 years ]
    To evaluate and compare median response duration, which is defined as the time between the date a response (CR or PR) was first seen until date of progression, between the two arms

  • Toxicity [ Time Frame: 5 years ]
    To evaluate the tolerability and toxicity in each arm as measured according to CTCAE v4.0.

  • Health-related quality of life [ Time Frame: 5 years ]
    To compare health-related quality of life (HR-QoL) between the experimental and control arms.

  • immunogenicity [ Time Frame: 5 years ]
    To measure and compare treatment-related tumor-specific immune response (immunogenicity) in each arm

  • Immunological biomarkers [ Time Frame: 5 years ]
    To identify immunological biomarkers as predictors of treatment response or resistance.

  • Cost-effectiveness [ Time Frame: 5 years ]
    To evaluate the cost-effectiveness and cost-utility of the addition of SAbR to Nivolumab in patients with mRCC


Estimated Enrollment: 35
Actual Study Start Date: June 20, 2016
Estimated Study Completion Date: December 2022
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nivolumab and SABR
Nivolumab alone: IV, 3 mg/kg q2 weeks, until disease progression or unacceptable toxicity. SABR, dose variable, in 1-3 fractions.
Drug: Nivolumab
Nivolumab IV, 3 mg/kg q2 weeks
Other Name: Opdivo
Radiation: SAbR
SAbR (1-3 lesions)
Other Names:
  • SBRT
  • Stereotactic Ablative Radiation Therapy

Detailed Description:
A single institution, safety lead-in phase II trial with SAbR to multiple metastatic sites concurrently administered with Nivolumab for patients with metastatic clear cell renal cell cancer who have failed at least one anti-angiogenic therapy.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At least 18 years of age
  • Willing and able to provide consent
  • Pathologic diagnosis of metastatic RCC with clear cell component
  • Measurable disease in at least 2 non-radiated sites. Progression or intolerance to at least one prior systemic anti-angiogenic therapy.
  • Eligible for extra-CNS SAbR to 1-6 sites of disease
  • Must have received at least one prior anti-angiogenic therapy in the advanced or metastatic setting. Prior cytokine therapy (eg, IL-2, IFN-α), vaccine therapy, or treatment with cytotoxic therapy is also allowed but not any other drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Previous treatment with surgery, radiation, chemotherapy, targeted agents (see above) are allowed provided that: Chemotherapy/Major surgery was administered > 14 days before the start Nivolumab; Minor surgery, radiation, or any targeted agents were administered > 7 days before the start of Nivolumab
  • Performance status ECOG 0, 1, 2 or 3.
  • Adequate organ and marrow function as defined below (obtained within 14 days of first dose of drug):

    • leukocytes≥ 2,000/mcL
    • absolute neutrophil count ≥ 1,500/mcL
    • platelets ≥ 50,000/mcl
    • total bilirubin ≤ 2mg/dL
    • AST(SGOT)/ALT(SPGT) ≤ 3 X institutional upper limit of normal
  • Women of child-bearing potential

    • female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
    • must have a negative serum or urine pregnancy test within 24 hours prior to the start of investigational product.
    • Women must not be breastfeeding.
    • must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and contraception should be continued for a period of 30 days plus the time required for the investigational drug to undergo five half lives.
    • Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
    • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Contraception should be continued for a period of 90 days plus the time required for the investigational drug to undergo five half lives. This is equivalent to 31 weeks after discontinuation of Nivolumab.
  • Adequate Renal function with Cr ≤ 2.5 mg/dL.

Exclusion Criteria:

  • Subjects who have had major surgery (such as nephrectomy) or chemotherapy within 2 weeks prior to first dose of drug
  • Subjects who have had radiation therapy within 2 weeks prior to first dose of drug
  • Uncontrolled adrenal insufficiency or active chronic liver disease
  • Any history of CNS metastases that is not adequately treated with surgery or SABR >14 days prior.
  • Prior treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Any positive history for HIV/AIDS, HTLV, hepatitis B or hepatitis C virus indicating acute or chronic infection.
  • Any active known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalent are permitted (although not encouraged) in the absence of active autoimmune disease.
  • Subjects with life expectancy < 6 months
  • Subjects receiving any other investigational or standard antineoplastic agents.
  • Prior malignancies active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, breast?, or etc.
  • Psychiatric illness/social situations that would limit consenting and compliance with study requirements.
  • Patients with history of hypersensitivity to monoclonal antibodies
  • Subjects who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02781506


Contacts
Contact: Raquibu Hannan, MD, PhD 214-645-8525
Contact: Irma Smith, MS 214-645-8525 irma.charles@utsouthwestern.edu

Locations
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Raquibul Hannan, MD    214-645-8525      
Contact: Jean Wu, MSN    214-645-8525      
Principal Investigator: Raquibul Hannan, MD, PhD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Raquibu Hannan, MD, PhD UT Southwestern Medical Center at Dallas
  More Information

Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT02781506     History of Changes
Other Study ID Numbers: STU 122015-052
First Submitted: May 19, 2016
First Posted: May 24, 2016
Last Update Posted: June 23, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs