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Clear Cell Renal Cell CarcinomaPhase 1NCT02595918

Nivolumab in Treating Patients With High-Risk Kidney Cancer Before Surgery

A Phase 1 study testing Metastasectomy, Nephrectomy and Nivolumab in people with Clear Cell Renal Cell Carcinoma and Metastatic Renal Cell Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Metastasectomy, Nephrectomy and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited States
Study dates
19 May 2016to 1 Aug 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Hemoglobin >= 9.0 g/dL (patients may be transfused to meet this criterion)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (except patients with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
  • Creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula)
  • The effects of nivolumab on the developing human fetus are unknown; for this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP should use an adequate method to avoid pregnancy for 23 weeks after the last dose of investigational drug; women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 14 days prior to the start of nivolumab; women must not be breastfeeding; men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception
  • Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level greater than 40 mIU/mL
  • WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; these durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days
  • Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • 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
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  • 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
  • Patients are permitted to enroll if they have 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 (precipitating event)
  • Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
  • Diagnosis of any second malignancy within the last 5 years prior to cycle 1, day 1, with the exception of those with a negligible risk of metastasis or death, per investigator's discretion (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
  • Use of live vaccines against infectious disease (e.g. varicella) within 28 days of initiation of study therapy; killed vaccinations (e.g. influenza) are allowed at any appropriate time before and during the study
  • Life expectancy < 3 months, per consenting investigator's opinion

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Pilot Study of Preoperative Nivolumab in High-Risk Non-Metastatic and Metastatic Renal Cell Carcinoma

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

  1. 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.

Being tested
Metastasectomy, Nephrectomy, Nivolumab
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetastasectomyProcedure or surgery

    Undergo metastasectomy

  • NephrectomyProcedure or surgery

    Undergo nephrectomy

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

Study groups in NCT02595918
Study groupRoleWhat they receive
Treatment (nivolumab)ExperimentalPatients receive nivolumab 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.
Receives: Procedure: Metastasectomy; Procedure: Nephrectomy; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Feasibility of a patient to receive at least 3 doses of nivolumab and complete surgery without significant delay attributable to nivolumab therapy

    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).

    Measured: Up to 8 weeks

Secondary outcomes (4)

  1. Incidence of toxicity

    Will be defined per Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 beginning April 1, 2018). All patients who receive any amount of the study drug will be evaluable for toxicity. Toxicity will be summarized according to grade as a number and percentage of participants. Each adverse event will be summarized as the highest grade experienced for an individual patient. Descriptive statistics will be used for summaries of the reported toxicity.

    Measured: Up to 90 days

  2. Surgical complications

    Defined per Clavien-Dindo Complications score.

    Measured: Up to 90 days

  3. Overall response rate

    Will be measured by radiographic response assessment for each cross sectional scan obtained using Response Evaluation Criteria in Solid Tumors 1.1. All patients will be categorized per their best radiographic response (complete response/partial response/stable disease/progressive disease), and the frequency of each category will be determined. The overall response rate will be calculated by dividing the sum of all patients achieving a complete response or confirmed partial response by the number of all evaluable patients.

    Measured: Up to 2 years

  4. Recurrence free survival

    Recurrence free survival will be estimated using the Kaplan-Meier method. Two-year recurrence free survival will be provided along with 95% confidence interval. Patients who are unable to undergo nephrectomy or metastasectomy for any reason will not be included in the analysis.

    Measured: Time from the start of the treatment to recurrence or death, assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2015 (estimated)
  2. Study start19 May 2016
  3. Primary completion1 Aug 2020
  4. Study completion1 Aug 2020

Why it stopped: Inadequate accrual rate

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02595918
Sponsor's protocol ID
NCI-2015-01913
Other IDs
NCI-2015-01913, 16-195, 16-195 A(1), 9913, 9913, P30CA008748
Status last verified
Oct 2020
First submitted
3 Nov 2015
Last updated
23 Oct 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Golkaram M, Kuo F, Gupta S, Carlo MI, Salmans ML, Vijayaraghavan R, Tang C, Makarov V, Rappold P, Blum KA, Zhao C, Mehio R, Zhang S, Godsey J, Pawlowski T, DiNatale RG, Morris LGT, Durack J, Russo P, Kotecha RR, Coleman J, Chen YB, Reuter VE, Motzer RJ, Voss MH, Liu L, Reznik E, Chan TA, Hakimi AA. Spatiotemporal evolution of the clear cell renal cell carcinoma microenvironment links intra-tumoral heterogeneity to immune escape. Genome Med. 2022 Dec 19;14(1):143. doi: 10.1186/s13073-022-01146-3.

    PubMed 36536472

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Metastasectomy, Nephrectomy and Nivolumab in people with Clear Cell Renal Cell Carcinoma and Metastatic Renal Cell Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Inadequate accrual rate). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02595918, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2020.

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