AzTrials
AzTrials

Brain MetastasesPhase 2NCT05048212

A Phase II Study of Nivolumab With Ipilimumab and Cabozantinib in Patients With Untreated Renal Cell Carcinoma Brain Metastases

A Phase 2 study testing Nivolumab, Ipilimumab and Cabozantinib in people with Brain Metastases and Renal Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

A Phase II Study of Nivolumab with Ipilimumab and Cabozantinib in Patients with Untreated Renal Cell Carcinoma Brain Metastases Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain Metastases, Renal Cell Carcinoma
What is being tested?
Nivolumab, Ipilimumab and Cabozantinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
20 Sep 2022to 31 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Signed Informed Consent Form (ICF)
  • Ability and willingness to comply with the requirements of the study protocol
  • Age ≥18 years
  • Life expectancy >12 weeks
  • Asymptomatic and off steroids for at least 10 days except patients: who have mild symptoms from intracranial disease that do not affect their performance status
  • Prior therapies for extracranial metastatic renal cell carcinoma as long as it did not include anti- CTLA-4 or cabozantinib or MET inhibitors
Show all 26Show fewer
  • Patients with histologically confirmed metastatic renal cell carcinoma and at least one measurable intracranial target lesion for which all of the following criteria are met:
  • Previously untreated or progressive after previous local therapy(limited to SRS and surgery)
  • Immediate local therapy clinically not indicated or patient is not a suitable candidate to receive immediate local therapy.
  • 5mm to 30mm, as determined by MRI with contrast.
  • Adequate hematologic and essential organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (C1D1)
  • Absolute neutrophil count (ANC) ≥1500 cells/µL
  • White blood cell (WBC) counts >2500/µ -- Lymphocyte count ≥500/µL
  • Platelet count ≥ 100,000/µL;
  • Hemoglobin ≥9.0 g/dL
  • Serum albumin≥2.8g/dl
  • Total bilirubin ≤1.5×upper limit of normal (ULN) with the following exception:
  • Patients with known Gilbert disease who have serum bilirubin level ≤3×ULN may be enrolled.
  • Alanine aminotransferase (ALT) ≤ 3x upper limit of normal (ULN).
  • Aspartate aminotransferase (AST) ≤ 3x upper limit of normal (ULN).
  • Alkaline phosphatase ≤5×ULN in patients with documented bone metastases.
  • Serum creatinine ≤ 1.5x ULN or calculated creatinine clearance ≥ 40mL/min (≥ 0.675mL/sec) using the Cockcroft-Gault equation: Males: (140 - age) x weight (kg)/(serum creatinine [mg/dL] × 72)Females: [(140 - age) x weight (kg)/(serum creatinine [mg/dL] × 72)] × 0.85
  • Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g.
  • For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for at least 12 months after the last dose of Cabozantinib and Nivolumab
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 (see Appendix 5)
  • INR and aPTT ≤1.5×ULN within 7 days prior to study enrollment 12. Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.

Who cannot join

  • Symptomatic brain metastases requiring immediate local interventions such as craniotomy or SRS or whole brain radiation.
  • Patients who require immediate surgical or radiotherapy interventions for extra-cranial lesions.
  • Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
  • Requiring corticosteroid dose in 10 days prior to administration of first dose of study drug with following exceptions
  • Symptomatic patients who have stable or decreasing corticosteroid use in the past 10 days may be included
  • Patients with Leptomeningeal disease.
Show all 41Show fewer
  • Any approved anticancer therapy, including chemotherapy and hormonal therapy within 4 weeks prior to initiation of study treatment; however, the following are allowed:
  • Hormone-replacement therapy or oral contraceptives
  • Herbal therapy >1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to Cycle 1,Day 1)
  • Current, recent (within 3 weeks of the first infusion of this study), or planned participation in an experimental drug study.
  • AEs from prior anticancer therapy that have not resolved to Grade ≤1 except for alopecia.
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; >Childes A cirrhosis; fatty liver; and inherited liver disease.
  • Patients with acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma.
  • Patients who are pregnant, lactating, or breastfeeding.
  • Known hypersensitivity to recombinant human antibodies.
  • Inability to undergo MRI secondary to Metal implant and Gadolinium contrast allergy.
  • Inability to comply with study and follow-up procedures.
  • History of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome,
  • Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis with the following exception:
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
  • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • Rash must cover less than 10% of body surface area (BSA), Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%).
  • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan with the following exception
  • -History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
  • History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection with the following exception:
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Active tuberculosis.
  • Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
  • Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1 with the following exception.
  • Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live, attenuated vaccine will be required during the study
  • Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study and at least 5 months after last dose of nivolumab.
  • Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score
  • ≤ 6, and prostate-specific antigen [PSA] ≤ 10 mg/mL, etc.).
  • Life expectancy of less than 12 weeks

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jianbo Wang contact

(713) 792-3393

jwang38@mdanderson.org

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Jianbo Wang, MD, 713-792-3393, jwang38@mdanderson.org

    Jianbo Wang, MD

    Recruiting

Other trials in United States

About this study

A Phase II Study of Nivolumab with Ipilimumab and Cabozantinib in Patients with Untreated Renal Cell Carcinoma Brain Metastases

Read the detailed description

This is a phase II study to assess the safety and efficacy of the combination of nivolumab with ipilimumab and cabozantinib in patients with untreated brain metastases from RCC until disease progression or intolerable toxicities or patient withdrawal. We will accrue a total of 40 patients. Patients will be treated with nivolumab (3mg/kg) and ipilimumab (1mg/kg) IV every 3 weeks for 4 doses and cabozantinib 40mg daily. Then patients will be treated with nivolumab 480mg IV Q 4 weeks and cabozantinib 40mg daily until progression or intolerable toxicities or patient's withdrawal. A lead-in group of 6 patients will be closely monitored for DLT. If stopping criteria (>3 patients develop DLTs) is met then, treatment will be switched to Nivolumab plus Cabozantinib omitting ipilimumab.

Being tested
Nivolumab, Ipilimumab, Cabozantinib
Medical subject headings
Brain Neoplasms, Carcinoma, Renal Cell

What participants receive

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

Study groups in NCT05048212
Study groupRoleWhat they receive
NivolumabExperimentalby vein every 3 weeks for 4 doses
Receives: Drug: Nivolumab; Drug: Ipilimumab; Drug: Cabozantinib
IpilimumabExperimentalby vein over 30 minutes every 3 weeks for 4 doses
Receives: Drug: Nivolumab; Drug: Ipilimumab; Drug: Cabozantinib
CabozantinibExperimentaltablets by mouth 1 time every day.
Receives: Drug: Nivolumab; Drug: Ipilimumab; Drug: Cabozantinib

What is being measured

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

  1. To associate if the combination of nivolumab with ipilimumab and cabozantinib produces improvesintracranial progression-free survival (PFS) in patients.

    Measured: through study completion, an average of 1 year

Timeline

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

  1. First posted17 Sep 2021
  2. Study start20 Sep 2022
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

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
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05048212
Sponsor's protocol ID
2021-0520
Other IDs
NCI-2021-10708
Status last verified
Sep 2026
First submitted
2 Sep 2021
Last updated
18 Sep 2026
Results posted
No
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 Nivolumab, Ipilimumab and Cabozantinib in people with Brain Metastases and Renal Cell Carcinoma, 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 26 inclusion and 41 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: looking for participants now, as of the sponsor's last update on 18 Sep 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Jianbo Wang ((713) 792-3393, jwang38@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To associate if the combination of nivolumab with ipilimumab and cabozantinib produces improvesintracranial progression-free survival (PFS) in patients. (time frame: through study completion, an average of 1 year). 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 NCT05048212.

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 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in