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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT02575222

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Location

Arm

52.2

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Clear Cell Renal Cell Carcinoma	Drug: Nivolumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

17 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 1, 2016

Actual Primary Completion Date :

Jun 9, 2020

Actual Study Completion Date :

Jun 9, 2020

Arms and Interventions

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: MDX-1106 BMS-936558 Opdivo

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:

MDX-1106

BMS-936558

Opdivo

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria (abbreviated):

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

Exclusion Criteria (abbreviated):

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