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Papillary Renal Cell CarcinomaPhase 2NCT04413123

Cabozantinib In Combo With NIVO + IPI In Advanced NCCRCC

A Phase 2 study testing Cabozantinib, Nivolumab and Ipilimumab in people with Papillary Renal Cell Carcinoma and Unclassified Renal Cell Carcinoma, run by Bradley A. McGregor, MD at 4 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This research study will assess whether cabozantinib, nivolumab and ipilimumab in combination are safe and effective in slowing down the growth of kidney cancer(renal cell carcinoma or RCC) that has advanced or spread to other areas the body. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cabozantinib, Nivolumab and Ipilimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
4 sitesUnited States
Study dates
5 Nov 2020to 20 Jun 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

  • histologically or cytologically confirmed unresectable advanced or metastatic nccRCC, including but not limited to:
  • Papillary RCC, any type
  • Unclassified RCC
  • Translocation RCC
  • Chromophobe RCC
  • Collecting duct RCC
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  • Renal cell carcinoma with 80% or more sarcomatoid features on primary nephrectomy specimen or a biopsy
  • Other nccRCC histologies in discussion with principal investigator
  • Measurable disease as per RECIST 1.1. See Section 11 for the evaluation of measurable disease.
  • Age ≥ 18 years
  • ECOG performance status ≤1 (Karnofsky ≥70%, see Appendix A)
  • Participants must undergo fresh tumor biopsy after registration but prior to the start of treatment unless medically unsafe or not feasible. If a fresh tumor biopsy is not medically safe or not feasible, confirmation of the availability of archival tumor tissue is required. For archival tissue, a recommended minimum of 20 unstained slides should be obtained.
  • Normal organ and marrow function as defined below:
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • hemoglobin ≥9g/dL (transfusions allowed)
  • total bilirubin ≤2.0 x institutional upper limit of normal with the following exception: patients with known Gilbert disease should have a serum bilirubin ≤ 3 x ULN
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal with the following exception: patients with known liver metastases should have AST and ALT ≤ 5 x ULN
  • creatinine clearance ≥30 mL/min/1.73 m2 according to the Cockcroft-Gault equation.
  • Normal coagulation INR ≤ 1.5
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 5 months after the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 months after completion of cabozantinib, nivolumab or ipilimumab administration.
  • Ability to understand and willingness to sign a written informed consent document

Who cannot join

  • Patients could be untreated or have received prior lines of therapies. Patients who receive prior therapy may receive only one VEGF based therapy. A combination therapy (e.g.
  • lenvatinib+everolimus) is considered 1 line of therapy.
  • Previous therapy with CD137 agonists and immune checkpoint inhibitors, including but not limited to inhibitors of the PD-1/PD-L1 and/or CTLA-4 axes. Previous treatment with IFNα or IL-2 is allowed if received > 4 weeks from enrollment.
  • Treatment with small molecule tyrosine kinase inhibitors within 2 weeks of enrollment, or any other anticancer agent within 4 weeks of enrollment.
  • Prior therapy with cabozantinib
  • Patients receiving any other therapeutic investigational agents.
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  • Treatment with hydroxychloroquine within two weeks of treatment start.
  • Radiotherapy for nccRCC within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
  • Untreated brain metastases. Patients might be included if they underwent radiation therapy or surgery at least 4 weeks prior enrollment. Stability of the central nervous system disease should be confirmed by brain MRI or CT-scan or as determined by treating investigator. Patients should not be receiving prednisone dose >10 mg/d at C1D1.
  • Other malignancy diagnosed within 2 years of first study treatment unless negligible risk of metastases or death (included but not limited to carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma, or other malignancy not deemed to impact patients 5-year life expectancy).
  • Significant cardiovascular disorders including:
  • Significant cardiovascular disease including dyspnea of New York Heart Association (NYHA) class II or greater, myocardial infarction within the previous 3 months of first study treatment, unstable arrhythmias, unstable angina. Patients with known coronary artery disease or congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50%, must be on a stable and optimized in the opinion of the treating physician, in consultation with a cardiologist when appropriate.
  • Uncontrolled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg). Anti-hypertensive therapy is allowed.
  • Personal history of hypertensive crisis or hypertensive encephalopathy within the previous 3 months of registration.
  • Personal history of stroke or transient ischemic attack within 3 months of registration.
  • Significant vascular disease, such as but not limited to aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis, within 6 months of registration.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG). Furthermore, subjects with a history of additional risk factors for torsades de pointes (eg, long QT syndrome) are also excluded.
  • Known history of severe allergic reactions attributed to compounds of similar chemical or biologic composition human antibodies, or known hypersensitivity to any component of cabozantinib, nivolumab or ipilimumab products.
  • Systemic immunosuppressive medications including but not limited to: Corticosteroids at a dose > 10mg equivalent prednisone daily, cyclosporin, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor (TNF) agents, hydroxychloroquine, within 2 weeks of first study dose.
  • Patients who have received acute, low-dose systemic immunosuppressant medications may be enrolled.
  • Patients with adrenal insufficiency on physiologic replacement doses of steroids may be enrolled.
  • The use of inhaled, topical, intraocular, or intraarticular corticosteroids or mineralocorticoids are allowed
  • Prior allogenic stem cell or solid organ transplant.
  • Personal history of autoimmune disease including: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on thyroid replacement hormone, or those with autoimmune dermatologic conditions not requiring the use of prednisone > 10 mg or equivalent are eligible.
  • History of idiopathic pulmonary fibrosis, organized pneumonia, or evidence of active pneumonitis on screening imaging CT of the chest. History of radiation pneumonitis in the radiation field is permitted.
  • History of following infectious diseases:
  • Active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening).
  • Active hepatitis C infection. Patients with positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
  • Infection requiring therapeutic oral or IV anti-microbials within 2 weeks of first study treatment. Patients receiving routine antimicrobial prophylaxis for dental procedures are eligible.
  • Known positive test for HIV.
  • Administration of a live, attenuated vaccine within 3 weeks for first study treatment.
  • Bleeding diathesis, or significant coagulopathy in the absence of therapeutic anticoagulation.
  • Use of strong inhibitors and inducers of CYP3A4
  • Significant bleeding, including but not limited to hematemesis, hematuria, hemoptysis of > 0.5 teaspoon (2.5 mL), within 3 months before registration.
  • Invasion of major pulmonary blood vessels. A discussion with PI may be needed if invading lesions are suspected.
  • Concomitant use of dipyramidole, ticlopidine, clopidogrel, cilostazol is excluded. Aspirin (≤ 325 mg per day) is allowed. Prophylactic anticoagulation with oral or parenteral anticoagulants for the patency of venous access devices or other indications is allowed.
  • Therapeutic use of low-molecular weight heparin (such as enoxaparin) and subcutaneous or oral Factor Xa inhibitors are allowed. Use of warfarin is prohibited.
  • Significant GI conditions at risk of perforation or bleeding, including but not limited to:
  • Active GI obstruction or requirement of routine parenteral nutrition or tube feedings.
  • Personal history of abdominal or tracheoesophageal fistula or GI perforation within 6 months of registration.
  • Evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
  • Serious, non-healing or dehiscing wound or active ulcer.
  • Major surgical procedure to include major dental, oral or maxillofacial procedures within 14 days of first study treatment.
  • Proteinuria as demonstrated by > 1.5 gram of protein in a 24-hour urine collection. All patients with ≥ 2+ protein on urinalysis must undergo 24-hour urine collection for protein.
  • Unable to swallow pills.
  • Malabsorption syndrome.
  • Inability to receive IV medications
  • Pregnant or lactating women.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02115

  • Brigham & Woman's Hospital

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • UT Southwestern Medical

    Dallas, Texas, 75390

Other trials in United States

About this study

Official title: A Phase 2 Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Advanced Non-Clear Cell Renal Cell Carcinoma

This research study will assess whether cabozantinib, nivolumab and ipilimumab in combination are safe and effective in slowing down the growth of kidney cancer(renal cell carcinoma or RCC) that has advanced or spread to other areas the body.

Read the detailed description

This research study involves an investigational drug combination not approved by the FDA (the U.S. Food and Drug Administration) for your kidney cancer.

The names of the study drugs in this investigational combination are:

  • Cabozantinib
  • Nivolumab
  • Ipilimumab

The research study procedures include screening for eligibility, study treatment, participant evaluations and safety follow-up visits, in addition to general health status follow-up after study treatment.

It is expected that about 40 people will take part in this research study.

Keywords
Papillary Renal Cell Carcinoma, Unclassified Renal Cell Carcinoma, Translocation Renal Cell Carcinoma, Chromophobe Renal Cell Carcinoma, Collecting duct Renal Cell Carcinoma, Renal Cell Carcinoma, Unresectable Advanced Renal Cell Carcinoma, Metastatic ncc Renal Cell Carcinoma
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.

  • CabozantinibDrug

    Also called COMETRIQ™, CABOMETYX™

    Cabozantinib predetermined protocol dosage po daily

  • NivolumabDrug

    Also called Opdivo®

    Nivolumab predetermined protocol dosage via IV every 3 weeks

  • IpilimumabDrug

    Also called Yervoy

    Ipilimumab predetermined protocol dosage via IV every 3 weeks

Study groups in NCT04413123
Study groupRoleWhat they receive
CabozantinibExperimentalEligible patients will be enrolled and receive treatment with * Cycle 1-4 (cycles of 21 days) * Cabozantinib predetermined protocol dosage po daily * Nivolumab predetermined protocol dosage via IV every 3 weeks * Ipilimumab predetermined protocol dosage via IV every 3 weeks * After the first four cycles of therapy, * Cabozantinib determined protocol dosage po daily * Nivolumab predetermined protocol dosage via IV every 3 weeks (cycles of 28 days)
Receives: Drug: Cabozantinib; Drug: Nivolumab; Drug: Ipilimumab

What is being measured

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

  1. Overall Response Rate

    Percent of patients who achieve overall response (CR or PR) by RECIST 1.1 will be summarized with 80% two-sided exact binomial confidence intervals (CI)

    Measured: tart of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started up to 21 Months

Secondary outcomes (7)

  1. Duration of response (DOR)

    will be estimated using the method of Kaplan-Meier, for all patients and by histology subtypes. M

    Measured: first documentation of response, to the earlier of the first documentation of disease progression or death from any cause, and calculated for patients with a best confirmed response of CR up to 21 Months

  2. Progression-free survival (PFS)

    the method of Kaplan-Meier, for all patients and by histology subtypes evaluation.

    Measured: trial treatment start to the earlier of progression or death due to any cause per investigator assessment. Participants alive without disease progression are censored at date of last disease evaluation up to 21 Months

  3. Overall survival (OS)

    the method of Kaplan-Meier, for all patients and by histology subtypes

    Measured: from trial treatment start to death due to any cause or censored at date last known alive up to 21 Months

  4. "Number of Participants with TreatmentRelated Adverse Events as Assessed by CTCAE version 5.

    For toxicity reporting, all adverse events will be graded and analyzed using CTCAE version 5.

    Measured: Baseline, day 1 of every cycle (21 days for first 4 cycles and then 28 days for each cycle tehreafter) and End of Treatment up 21 months

  5. Quality of life- FKSI-19 Scale

    The Functional Assessment of Cancer Therapy-Kidney Symptom (FKSI-19) is a 19 item questionnaire with each item scored on a scale of 0-4 for a total score of 0-76 with higher scores indicating fewer symptom

    Measured: 12 weeks for the first assessment, then every 8 weeks (+/- 7 days) for the first 6 months. Then take place every 12 weeks (+/- 7 days)

  6. Quality of life-BFI Questionaire

    The Brief Fatigue Inventory (BFI) is a 9-item questionnaire with each item scored on a scale of 0-10.

    Scores are categorized as mild (1-3), moderate (4-6), or severe (7-10). A global fatigue score can be found by averaging the score obtained on each test item completed

    Measured: 2 weeks for the first assessment, then every 8 weeks (+/- 7 days) for the first 6 months. Then take place every 12 weeks (+/- 7 days)

  7. Objective response rate (ORR)

    ORR by RECIST 1.1 according to histology subtypes (Papillary RCC versus other histology types) will be summarized with 80% two-sided exact CIs.

    Measured: defined as the percentage of patients with partial (PR) or complete response (CR) as best overall response according to RECIST 1.1 by investigator assessment up to 21 Months

Timeline

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

  1. First posted2 Jun 2020
  2. Study start5 Nov 2020
  3. Primary completion20 Dec 2026 (estimated)
  4. Study completion20 Jun 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04413123
Sponsor's protocol ID
19-789
Status last verified
Jan 2026
First submitted
26 Mar 2020
Last updated
23 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib, Nivolumab and Ipilimumab in people with Papillary Renal Cell Carcinoma and Unclassified Renal Cell Carcinoma, run by Bradley A. McGregor, MD at 4 sites 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 48 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: under way, not looking for participants, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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?

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?

Overall Response Rate (time frame: tart of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started up to 21 Months). 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 NCT04413123.

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 Jul 2026.

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