A Pilot Study of Preoperative Nivolumab in High-Risk Non-Metastatic and Metastatic Renal Cell Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Clear Cell Renal Cell Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 19
- Locations
- 1
- Primary Endpoint
- Feasibility of a patient to receive at least 3 doses of nivolumab and complete surgery without significant delay attributable to nivolumab therapy
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
This pilot phase I trial studies the side effects of nivolumab and how well it works in treating patients with high-risk kidney cancer before surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed Description
PRIMARY OBJECTIVE: I. To study the safety and feasibility of preoperative nivolumab administration in subjects with resectable, high-risk, non-metastatic and metastatic renal cell carcinoma undergoing planned cytoreductive nephrectomy or metastasectomy. SECONDARY OBJECTIVES: I. To assess overall response rate in patients receiving preoperative nivolumab. II. To assess recurrence free survival at 2 years in patients receiving preoperative nivolumab in patients with high-risk, non-metastatic disease. EXPLORATORY OBJECTIVES: I. To evaluate the association between baseline tumor mutational burden and both immune infiltration and radiographic tumor response to nivolumab. II. To explore predicted and expressed tumor neoantigens and their correlation with radiographic tumor response to nivolumab. III. To explore the association between the predicted immune signature (via ribonucleic acid sequencing \[RNAseq\]) in the tumor microenvironment with radiographic tumor response to nivolumab. IV. To determine whether changes in the tumor microenvironment before, during, and after therapy are associated with response. V. To assess the potential association between PD-L1 expression (by immunohistochemistry \[IHC\]) and radiographic tumor response to nivolumab. OUTLINE: Patients receive nivolumab intravenously (IV) over 30 minutes on days -56, -42, -28, and -14 in the absence of disease progression or unacceptable toxicity. Patients then undergo nephrectomy or metastasectomy on day 0. After completion of study treatment, patients are followed up at 14-28 days, at 90 days, and then at 24-28 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically or cytologically confirmed clear cell renal cell carcinoma (RCC)
- •For non-metastatic patients, the preoperative Memorial Sloan-Kettering (MSK) nomogram estimates the patient's likelihood of freedom from metastatic recurrence within the first 12 years following radical or partial nephrectomy to be =\< 80%
- •Measurable disease, 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) as \>= 20 mm (\>= 2 cm) with conventional techniques or as \>= 10 mm (\>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- •Non-metastatic disease will be defined by no evidence of metastases other than regional lymphadenopathy as assessed by imaging of the chest, abdomen and pelvis with CT of the chest and CT or MRI of the abdomen; regional lymph nodes, per 7th edition American Joint Committee on Cancer (AJCC) staging manual (2010) for kidney cancer, include the following positions: renal hilar, precaval, paracaval, retrocaval, interaortocaval, paraaortic, preaortic, and retroaortic
- •Scheduled to undergo nephrectomy or metastasectomy as part of treatment plan, per assessment through an MSK urologic surgeon or medical oncologist listed as investigator on this trial
- •Availability of a frozen biopsy core prior to cycle 1, day 1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky \>= 80%)
- •Leukocytes \>= 2,500/mcL
- •Absolute neutrophil count \>= 1,500/mcL (without granulocyte colony-stimulating factor support within 2 weeks prior to cycle 1, day 1)
- •Platelets \>= 100,000/mcL (without transfusion within 2 weeks prior to cycle 1, day 1)
Exclusion Criteria
- •Prior receipt of systemic checkpoint inhibitor therapy for renal cell carcinoma
- •Inability to safely delay surgery by 8 weeks as per surgeon's discretion
- •Patients who are receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab
- •History of severe hypersensitivity reaction to any monoclonal antibody
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study because nivolumab has a potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab, breastfeeding should be discontinued if the mother is treated with nivolumab
- •Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- •Patients should be excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection
- •Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease; patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome, psoriasis controlled with topical medication, and patients with positive serology, such as antinuclear antibodies (ANA) or anti-thyroid antibodies, should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
Outcomes
Primary Outcomes
Feasibility of a patient to receive at least 3 doses of nivolumab and complete surgery without significant delay attributable to nivolumab therapy
Time Frame: Up to 8 weeks
Significant delay is defined as delay of \> 112 days after the first dose of nivolumab, which would constitute a doubling of the 'planned delay' that our design requires for administration of preoperative therapy (56 days).
Secondary Outcomes
- Overall response rate(Up to 2 years)
- Incidence of toxicity(Up to 90 days)
- Surgical complications(Up to 90 days)
- Recurrence free survival(Time from the start of the treatment to recurrence or death, assessed up to 2 years)