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Kidney Medullary CarcinomaPhase 2NCT03274258

Phase II Trial of Nivolumab Plus Ipilimumab in Patients With Renal Medullary Carcinoma

A Phase 2 study testing Ipilimumab and Nivolumab in people with Kidney Medullary Carcinoma and Loss of INI 1 Protein Expression, run by M.D. Anderson Cancer Center 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 phase II trial studies how well nivolumab and ipilimumab work in treating patients with kidney cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ipilimumab and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
29 May 2018to 21 Nov 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 give written informed consent prior to initiation of therapy, in keeping with the policies of the institution. Patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy.
  • Patients with locally advanced or metastatic RMC histologically confirmed by expert pathology review and loss of SMARCB1 staining by immunohistochemistry. Patients with advanced or metastatic unclassified renal cell carcinoma with medullary phenotype (a rare SMARCB1 negative RMC variant occurring in individuals without sickle hemoglobinopathies) are also eligible. The principal investigator (PI) is the final arbiter in questions related to eligibility.
  • Patients will be eligible regardless of whether they have had prior nephrectomy or still have their primary tumor in-situ.
  • Patients must have at least one measurable site of disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures >= 15 mm with conventional techniques or >= 10 mm with more sensitive techniques such as magnetic resonance imaging (MRI) or spiral computerized tomography (CT) scan. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
  • Patients should be willing to provide a newly obtained fresh core biopsy of a tumor lesion. Not required if there is a recently obtained fresh specimen on an Institutional Review Board (IRB) approved correlated trial up to 6 weeks (42 days) prior to initiation of treatment on day 1.
  • Patients can be either naive for any previous systemic treatment or have had any number of prior systemic therapies. However, patients must not have received prior anticancer therapy with anti-PD1, anti-PD-L1, or anti-CTLA-4 immune checkpoint inhibitors.
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  • There must be evidence of progression on or after last treatment regimen received. NOTE: If subject is unable to walk due to paralysis, but is mobile in a wheelchair, subject is considered to be ambulatory for the purpose of assessing their performance status.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Consent to MD Anderson companion laboratory protocol 2014-0938.
  • Hemoglobin >= 9 g/dl (treatment allowed) (within 14 days of the first dose of the study drugs).
  • Absolute neutrophil count >= 1000/mcL (within 14 days of the first dose of the study drugs).
  • Platelets >= 75,000/L (within 14 days of the first dose of the study drugs).
  • Total bilirubin =< 1.5 mg/dl (within 14 days of the first dose of the study drugs).
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (ULN), except in known hepatic metastasis, wherein may be =< 5 x ULN (within 14 days of the first dose of the study drugs).
  • Serum creatinine =< 1.5 x ULN by gender (as long as patient does not require dialysis) (within 14 days of the first dose of the study drugs); May receive transfusion; Without growth factor support (filgrastim or pegfilgrastim) for at least 14 days; If creatinine is not < 1.5 x ULN, then calculate by Cockcroft-Gault methods or local institutional standard and creatinine clearance (CrCl) must be > 30 mL/kg/1.73 m^2.
  • International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 x ULN prior to study entry. Therapeutic anticoagulation with warfarin is allowed if target INR =< 3 on a stable dose of warfarin or on a stable dose of low molecular weight (LMW) heparin for > 2 weeks (14 days) at the time of enrollment.
  • Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected or treated with radiosurgery or Gamma knife, without recurrence or edema for 1 month (4 weeks).
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of the study drug.
  • Women must not be breastfeeding.
  • WOCBP must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 30 days (duration of ovulatory cycle) for a total of 5 months post treatment completion.
  • Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 90 days duration of sperm turnover for a total of 5 months post-treatment completion.
  • Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However WOCBP must still undergo pregnancy testing as described in these sections.

Who cannot join

  • Patients must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, or adequately treated (without recurrence post-resection or post-radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
  • Patients currently receiving anticancer therapies or who have received anticancer therapies (including chemotherapy and targeted therapy) within 2 weeks (14 days) prior to study day are excluded. Patients who have completed palliative radiation therapy more than 14 days prior to the first dose of the combination ipilimumab plus nivolumab are eligible.
  • Patients, who have had a major surgery or significant traumatic injury (injury requiring > 4 weeks [28 days] to heal) within 4 weeks (28 days) of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that are expected to require major surgery, other than cytoreductive nephrectomy +/- retroperitoneal lymph node dissection, during the course of the study.
  • Patients who have organ allografts.
  • Known or suspected autoimmune disease. Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g., Wegener's granulomatosis) are excluded from this study. Patients with a history of Hashimoto's thyroiditis only requiring hormone replacement, type I diabetes, or psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are allowed to participate.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
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  • Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection. If hepatitis C antibody test is positive then active infection has to be confirmed by hepatitis C RNA testing for the patient to be excluded.
  • Any underlying medical condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea, uncontrolled nausea or vomiting.
  • Patients must not have received prior anticancer therapy with anti-PD1, anti-PD-L1, or anti- CTLA-4 immune checkpoint inhibitors.
  • Patients receiving any concomitant systemic therapy for renal cell cancer are excluded.
  • Patients must not be scheduled to receive another experimental drug while on this study.
  • Patients who are on high dose steroid (e.g., > 10 mg prednisone daily or equivalent) or other more potent immune suppression medications (e.g., infliximab). Topical, inhaled, intraarticular, ocular, or intranasal corticosteroids (with minimal systemic absorption) are allowed. A brief course (< 48 hours) of systemic corticosteroids for prophylaxis (e.g., from contrast dye allergy) is permitted. Physiological corticosteroid replacement therapy for adrenal insufficiency is also permitted.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: a) Symptomatic congestive heart failure of New York heart Association class III or IV; b) Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease; c) Severely impaired lung function as defined as oxygen (O2) saturation that is 92% or less at rest on room air; d) Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN; e) Systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement) despite appropriate antibiotics or other treatment; f) Known active or symptomatic viral hepatitis or chronic liver disease. Uncontrolled adrenal insufficiency.
  • Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ipilimumab or nivolumab or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
  • Patients should not receive immunization with attenuated live vaccines within one week (7 days) of study entry or during study period; Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods as defined above. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception.
  • Any patients who cannot be compliant with the appointments required in this protocol must not be enrolled in this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

This phase II trial studies how well nivolumab and ipilimumab work in treating patients with kidney cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, 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 OBJECTIVES:

  1. To determine the objective response rate (ORR) of patients with locally advanced or metastatic renal medullary carcinoma (RMC) treated with combination of nivolumab plus ipilimumab.

SECONDARY OBJECTIVES:

  1. To determine the efficacy and safety of the combination of nivolumab plus ipilimumab in patients with RMC.

II. To evaluate potential biomarkers for patient stratification and treatment response, as well as tumor antigen-specific immune responses, such as antibody and T cell responses, as surrogates for anti-tumor activity.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 60 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Being tested
Ipilimumab, 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.

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4

    Given IV

  • NivolumabBiological

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

    Given IV

Study groups in NCT03274258
Study groupRoleWhat they receive
Treatment (nivolumab, ipilimumab)ExperimentalPatients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Ipilimumab; Biological: Nivolumab

What is being measured

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

  1. Objective Response Rate (ORR)

    To determine the objective response rate (ORR) of patients with locally advanced or metastatic renal medullary carcinoma (RMC) treated with combination of nivolumab plus ipilimumab.

    Measured: 2 years and 6 months

  2. Overall Survival (OS), Progression-free Survival (PFS), and the Disease Control Rate (DCR)

    To determine the efficacy and safety of the combination of nivolumab plus ipilimumab in patients with RMC. Efficacy will be measured by overall survival (OS) and progression-free survival (PFS).

    Measured: 2 years and 6 months

  3. Disease Control Rate (DCR)

    To determine the efficacy and safety of the combination of nivolumab plus ipilimumab in patients with RMC. Efficacy will be measured by disease control rate (DCR).

    Measured: 2 years and 6 months

Secondary outcomes (1)

  1. Exploratory Biomarker Assessments Associated With Treatment Response

    Exploratory analyses of tumor and immune biomarkers associated with treatment response, including antibody and T-cell immune responses, were planned using protocol-specified laboratory assays.

    Measured: 2 years and 6 months

Timeline

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

  1. First posted6 Sep 2017
  2. Study start29 May 2018
  3. Primary completion21 Nov 2025
  4. Study completion21 Nov 2025

Why it stopped: The study met its prespecified futility criteria during the prespecified interim futility analysis after enrolling the first cohort of 10 patients.

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03274258
Sponsor's protocol ID
2017-0201
Other IDs
NCI-2018-01066, 2017-0201, P30CA016672
Status last verified
Sep 2026
First submitted
5 Sep 2017
Last updated
20 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ipilimumab and Nivolumab in people with Kidney Medullary Carcinoma and Loss of INI 1 Protein Expression, run by M.D. Anderson 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 22 inclusion and 18 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 20 Oct 2026. 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?

Yes. Results are posted in the registry (first posted 20 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Response Rate (ORR) (time frame: 2 years and 6 months). The study lists 3 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 NCT03274258.

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 20 Oct 2026.

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