Clinical trial NCT02575222: Study of Neoadjuvant Nivolumab in Patients With Non-metastatic Stage II-IV Clear Cell Renal Cell Carcinoma
Official title: Phase I Study of Neoadjuvant Nivolumab in Patients With Non-metastatic High-risk Clear Cell Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Clear Cell Renal Cell Carcinoma
Keywords: Immunotherapy
PD-1
anti-PD-1
antibody
Kidney Cancer
RCC
non-metastatic
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2015-10-14
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Safety as assessed by number of participants experiencing adverse events
timeFrame: From the first dose of nivolumab treatment through 100 days post-surgery
Secondary outcomes:
measure: Objective Tumor Response Rate (by RECIST)
timeFrame: Assessed at baseline, prior to surgery, and 3 months after surgery
measure: Objective Tumor Response Rate (by irRC)
timeFrame: Assessed at baseline, prior to surgery, and 3 months after surgery
measure: Quality of Life as assessed by the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) -15 questionnaire
timeFrame: Baseline, 2 weeks, 4 weeks, prior to surgery, and at 1-, 3-, 6-, and 12-months after surgery
measure: Metastasis-Free Survival
timeFrame: 12 months post-operatively, then every 6 months for 5 years
measure: Overall Survival
timeFrame: 12 months post-operatively, then every 6 months for 5 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Department of Urology and The Brady Urological Institute at Johns Hopkins
name: Mohamad E Allaf, M.D
role: PRINCIPAL_INVESTIGATOR
References: