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Metastatic Renal Cell CarcinomaPhase 2NCT03126331

Intermittent Therapy in Metastatic Renal Cell Carcinoma Patients Treated With Ipilimumab and Nivolumab

A Phase 2 study testing Nivolumab and Ipilimumab in people with Metastatic Renal Cell Carcinoma, run by Case Comprehensive Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is being done with patients with advanced kidney cancer (also called renal cell carcinoma or RCC). This is a research study involving the use of the drug Nivolumab (also known as Opdivo®). Nivolumab is an anti-PD-1 antibody. It works by attaching to and blocking a molecule called PD-1. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Renal Cell Carcinoma
What is being tested?
Nivolumab and Ipilimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
3 Aug 2017to 24 Oct 2023
Phase
Phase 2
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

  • Cohort 1:
  • Must have received at least one but not more than two prior anti-angiogenic therapy regimens (including, but not limited to, sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and bevacizumab) in the advanced or metastatic RCC setting. Prior cytokine therapy (eg, IL-2, IFN-a), vaccine therapy, or treatment with cytotoxics is also allowed.
  • No more than three total prior systemic treatment regimens in the advanced or metastatic RCC setting.
  • Cohort 2:
  • --Achieved SD, PR, or CR after administration of front-line therapy with Ipi/Nivo (up to 4 doses) for advanced/metastatic RCC followed by 24 weeks (+/- 8 weeks; minimum 3 infusions) of Nivo maintenance. Patient enrollment will occur after completion of 24 weeks (+/- 8 weeks; minimum 3 infusions) of maintenance nivolumab.
  • Histological confirmation of renal cell carcinoma (RCC) (any histology)
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  • Advanced or metastatic RCC.
  • Measurable disease as defined by RECIST 1.1 criteria
  • Must have received at least one but not more than two prior anti-angiogenic therapy regimens (including, but not limited to, sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and bevacizumab) in the advanced or metastatic RCC setting. Prior cytokine therapy (for example, Interleukin (IL)-2, interferon (IFN)-α), vaccine therapy, or treatment with cytotoxics is also allowed.
  • Patients treated with neoadjuvant and/or adjuvant therapy prior to development of metastatic disease may also be included provided that at least 12 months have elapsed since last dose. These regimens do not count toward total number of prior therapies permitted for trial inclusion.
  • No more than three total prior systemic treatment regimens in the advanced or metastatic RCC setting, and must have evidence of progression on or after the last treatment regimen received and within 6 months prior to study enrollment.
  • Karnofsky Performance Score (KPS) ≥70%
  • Women of childbearing potential (WOCBP) must use effective method(s) of contraception have a negative serum or urine pregnancy test within 24 hours prior to the start of therapy, and must not be breastfeeding. Pregnant women are excluded from this study because animal studies have demonstrated that nivolumab can cause fetal harm when administered to pregnant women. Breastfeeding women are excluded from this study because nivolumab may be excreted in human milk and the potential for serious adverse reactions in nursing infants.
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year
  • Willing and able to provide informed consent.
  • Laboratory criteria for study entry must meet the following criteria:
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min (measured or calculated using the Cockcroft-Gault formula).
  • white blood cell count ≥ 2000/µL
  • Neutrophils ≥ 1500/µL
  • Platelets ≥ 100,000/µL
  • Hemaglobin ≥ 9.0g/dL
  • Aspartate Aminotransferase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN
  • Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)

Who cannot join

  • Cohort 1 only:
  • --Prior treatment with an anti-programmed death (PD)-1, anti-programmed death ligand 1 (PD-L1), anti-programmed death ligand 2 (PD-L2), anti-Cluster of differentiation (CD137), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Anti-cancer therapy less than 14 days prior to the first dose of study drug (less than 28 days for bevacizumab) or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug.
  • History of severe hypersensitivity reaction to any monoclonal antibody.
  • Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no imaging evidence of progression for 28 days after treatment is complete and within 28 days prior to the first dose of nivolumab administration.
  • Major surgery (eg, nephrectomy) less than 28 days prior to the first dose of study drug.
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  • Any active known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition or prior therapy requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
  • Any known active chronic liver disease.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection.
  • Known medical condition (for example, a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
  • Strong Cytochrome P450 3A4 (CYP3A4) inhibitors

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

Other trials in United States

About this study

Official title: A Single-arm Phase II Trial of Intermittent Nivolumab in Patients With Metastatic Renal Cell Carcinoma Who Have Received Prior Anti-Angiogenic Therapy

This study is being done with patients with advanced kidney cancer (also called renal cell carcinoma or RCC). This is a research study involving the use of the drug Nivolumab (also known as Opdivo®). Nivolumab is an anti-PD-1 antibody. It works by attaching to and blocking a molecule called PD-1. PD-1 is a protein that is present on different types of cells in the immune system and controls parts of the immune system by shutting it down. Antibodies that block PD-1 can potentially prevent PD-1 from shutting down the immune system, thus allowing it to recognize and help destroy cancer cells. In many countries (including the United States, European Union and Japan) Nivolumab is approved to treat certain cancer types. The purpose of the study is to test the safety and effectiveness of nivolumab in patients with advanced RCC when given intermittently.

Nivolumab is approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced kidney cancer, non small cell lung cancer, classical Hodgkin Lymphoma and Metastatic Melanoma. Nivolumab is FDA-approved for advanced RCC because has been shown to shrink RCC tumors that have spread outside the kidney.

Read the detailed description

Primary Objective:

  • To determine the feasibility of intermittent nivolumab therapy in patients with metastatic renal cell carcinoma.

Secondary Objectives:

  • To determine the clinical outcome (overall response rate (ORR), progressive free survival (PFS), overall survival (OS)) in metastatic renal cell carcinoma patients treated with intermittent nivolumab therapy.
  • To evaluate the toxicity of intermittent nivolumab therapy in patients with metastatic renal cell carcinoma.

Correlative Objective

  • Investigate correlations between baseline and post-treatment immunomodulatory cells [specifically, myeloid-derived suppressor cells (MDSC) regulatory T cells (Treg), cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8), T Cells, T-cell receptor (TCR) repertoire and time off therapy.
Being tested
Nivolumab, Ipilimumab
Keywords
Kidney Cancer, Metastatic, Nivolumab
Medical subject headings
Carcinoma, Renal Cell, Kidney Neoplasms, Neoplasm Metastasis

What participants receive

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

  • NivolumabDrug

    Also called Opdivo®

    Nivolumab monotherapy will be administered dosed at 480mg IV over 30 minutes for all patients every 4 weeks, regardless of weight (when given in combination with ipilimumab, the dose of nivolumab is 3mg/kg every 3 weeks).

    Tumor assessed after 12 weeks If tumor decreases by 10% or more, then hold drug for 12 week and test tumor again. Continue treatment if tumor is not decreased by 10% or more.

  • IpilimumabDrug

    Ipilimumab is dosed at 1mg/kg over 30 minutes every 3 weeks

Study groups in NCT03126331
Study groupRoleWhat they receive
Cohort I: Intermittent NivolumabExperimentalNivolumab monotherapy. Participants who have initial 10% or greater tumor burden reduction will discontinue nivolumab until they experience a pre-specified disease progression at which time nivolumab will be restarted
Receives: Drug: Nivolumab
Cohort II: combination ipilimumab/nivolumabExperimentalCombination of ipilimumab/nivolumab for previously untreated intermediate and poor risk mRCC Includes participants treated front-line ipilimumab/nivolumab. Participants with treatment-naïve mRCC who receive up to four doses of induction ipilimumab/nivolumab and 24 weeks (+/- 8 weeks; minimum 3 infusions) of maintenance nivolumab and achieve stable disease (SD), complete response (CR), or partial response (PR) will be eligible for inclusion. Participants who achieve SD will continue with nivolumab maintenance per standard of care while those who achieve a PR or CR will enter an observation period off therapy. Upon disease progression, participants will be re-challenged with combination ipilimumab/nivolumab.
Receives: Drug: Nivolumab; Drug: Ipilimumab

What is being measured

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

  1. the proportion of patients who receive intermittent therapy

    For cohort I: Assess feasibility of an intermittent dosing schedule, where feasibility is defined in terms of the proportion of patients eligible for intermittent therapy who actually receive it. An underlying acceptance rate of >80% is arbitrarily considered necessary in order to accept the intermittent schedule as feasible whereas an acceptance rate <50% is considered evidence that the intermittent schedule is not feasible

    Measured: Expected duration 5.5 months

  2. Rate of participants who maintain CR/PR off therapy for at least 9 months

    For cohort II: Rate of participants who maintain CR/PR off therapy for at least 9 months

    Measured: Up to 9 months after treatment

Secondary outcomes (4)

  1. Change in tumor burden

    Measured: Expected duration 5.5 months

  2. Objective Response

    Number of patients with tumor response per the RECIST 1.1 Criteria:

    Complete response (CR) is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm.

    Partial response (PR) is defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesions

    Progressive disease (PD) is defined as a greater than or equal to 20% increase in the sum of the longest dimensions of the target lesions, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD

    Measured: Expected duration 5.5 months

  3. Length of Progression Free Survival

    Time from enrollment in the study to progression, when progression is defined as a greater than or equal to 20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: Expected duration 5.5 months

  4. Percent of patients who experience grade 3 AE or higher with re-induction ipi/nivo

    Estimate toxicity rate in participants undergoing reinduction with ipilimumab/nivolumab as measured by percent of patients who experience grade 3 AE or higher

    Measured: up to 100 days after end of treatment

Timeline

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

  1. First posted24 Apr 2017
  2. Study start3 Aug 2017
  3. Primary completion24 Oct 2023
  4. Study completion24 Oct 2023

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03126331
Sponsor's protocol ID
CASE5816
Status last verified
Mar 2024
First submitted
19 Apr 2017
Last updated
18 Mar 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Ornstein MC, George L, Wei W, Diaz-Montero CM, Rayman P, Martin A, Basu A, Beckermann KE, Nizam A, Wee CE, Gilligan TD, Gupta S, Rini BI. Phase II Trial of Intermittent Therapy in Patients with Metastatic Renal Cell Carcinoma Treated with Front-line Ipilimumab and Nivolumab. Clin Genitourin Cancer. 2024 Dec;22(6):102181. doi: 10.1016/j.clgc.2024.102181. Epub 2024 Jul 31.

    PubMed 39208489

  • Ornstein MC, Wood LS, Hobbs BP, Allman KD, Martin A, Bevan M, Gilligan TD, Garcia JA, Rini BI. A phase II trial of intermittent nivolumab in patients with metastatic renal cell carcinoma (mRCC) who have received prior anti-angiogenic therapy. J Immunother Cancer. 2019 May 16;7(1):127. doi: 10.1186/s40425-019-0615-z.

    PubMed 31097024

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Ipilimumab in people with Metastatic Renal Cell Carcinoma, run by Case Comprehensive Cancer Center 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 23 inclusion and 13 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: finished, as of the sponsor's last update on 18 Mar 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

the proportion of patients who receive intermittent therapy (time frame: Expected duration 5.5 months). The study lists 2 primary outcomes in all. 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 NCT03126331, which also lists 2 linked publications.

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 18 Mar 2024.

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