Study of Neoadjuvant Nivolumab in Patients With Non-metastatic Stage II-IV Clear Cell Renal Cell Carcinoma

Phase I Study of Neoadjuvant Nivolumab in Patients With Non-metastatic High-risk Clear Cell Renal Cell Carcinoma

This study will evaluate the use of nivolumab before surgery in patients with high-risk clear cell renal cell carcinoma who are eligible for nephrectomy. Nivolumab is an antibody that may help activate the immune system by blocking the function of an inhibitory molecule, Programmed cell death-1 (PD-1).

Study Overview

• Status: Completed
• Conditions: Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria (abbreviated):

1. Confirmed non-metastatic high-risk clear cell renal cell carcinoma (T2a-T4NanyM0 or TanyN1M0)
2. Schedule to undergo either partial or radical nephrectomy as part of treatment plan
3. Patient agrees to have a tumor biopsy
4. ECOG performance status of 0 or 1
5. Adequate organ and marrow function defined by study-specified laboratory tests
6. Must use acceptable form of birth control while on study and for approximately 31 weeks post-treatment completion
7. Willingness and ability to comply with scheduled visits, treatment plans, lab tests and other study procedures

Exclusion Criteria (abbreviated):

1. Other active malignancies within last 3 years (with some exceptions for skin, prostate, cervical, or breast cancer)
2. Need for urgent or emergent nephrectomy to relieve symptoms
3. Prior treatment for RCC including surgery, radiation, thermoablation or systemic therapy
4. Surgery within 28 days of starting study treatment (some exceptions for minor procedures)
5. Received live vaccine for infectious diseases within 28 days of starting study treatment
6. Prior treatment with any antibody or drug targeting T-cell costimulation or immune checkpoint pathways (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, etc)
7. Use of immunosuppressive doses of systemic medications within 14 days prior to starting study drug.
8. Current use of immunosuppressive agents
9. History of severe hypersensitivity reaction to other monoclonal antibodies
10. Current signs or symptoms of severe progressive or uncontrolled hepatic, hematologic, gastrointestinal, endocrine, pulmonary or cardiac disease other than directly related to RCC
11. Uncontrolled psychiatric illness/social situations that would limit compliance with study requirements.
12. Active infection requiring therapy.
13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
14. Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
15. History of autoimmune disease or syndrome requiring systemic steroids or immunosuppressants (some exceptions apply).
16. Pulse oximetry of <92% on room air
17. Pregnant or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab; 3 mg/kg, IV (in the vein) on day 1 of each 2-week cycle, for a total of 3 doses prior to nephrectomy.	Drug: Nivolumab; 3 mg/kg, IV (in the vein) on day 1 of each 2-week cycle, for a total of 3 doses prior to nephrectomy.; Other Names: BMS-936558; MDX-1106; Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by number of participants experiencing adverse events	Number of participants experiencing any adverse event as defined by Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)	From the first dose of nivolumab treatment through 100 days post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Tumor Response Rate (by RECIST)	Number of patients achieving a complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST)	Assessed at baseline, prior to surgery, and 3 months after surgery
Objective Tumor Response Rate (by irRC)	Number of patients achieving a complete response (CR) or partial response (PR) by immune-related response criteria (irRC)	Assessed at baseline, prior to surgery, and 3 months after surgery
Quality of Life as assessed by the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) -15 questionnaire	Total score range 0-60 with higher scores indicating a less symptomatic respondent.	Baseline, 2 weeks, 4 weeks, prior to surgery, and at 1-, 3-, 6-, and 12-months after surgery
Metastasis-Free Survival	Number of months without evidence of metastasis.	12 months post-operatively, then every 6 months for 5 years
Overall Survival	Number of months alive.	12 months post-operatively, then every 6 months for 5 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Mohamad E Allaf, M.D, Department of Urology and The Brady Urological Institute at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): June 9, 2020
• Study Completion (Actual): June 9, 2020

Study Registration Dates

• First Submitted: October 6, 2015
• First Submitted That Met QC Criteria: October 13, 2015
• First Posted (Estimate): October 14, 2015

Study Record Updates

• Last Update Posted (Actual): June 12, 2020
• Last Update Submitted That Met QC Criteria: June 10, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Immunotherapy; antibody; PD-1; Kidney Cancer; anti-PD-1; non-metastatic; RCC
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: J15179; IRB00068726 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO