Renal Cell CarcinomaPhase 2NCT06053658
Phase 2 Study of Combination Tivozanib and Nivolumab in Advanced Non-Clear Cell Renal Cell Carcinoma
A Phase 2 study testing Tivozanib and Nivolumab in people with Renal Cell Carcinoma, run by M.D. Anderson Cancer Center at 6 sites in United States.
Trial summary
To learn if giving tivozanib in combination with nivolumab can help to control advanced nccRCC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Tivozanib and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 6 sitesUnited States
- Study dates
- 5 Jan 2024to 1 Nov 2028
- 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
- Patients with histologically or cytologically confirmed metastatic non-clear cell renal cell carcinoma of papillary, chromophobe, oncocytic neoplasms, unclassified, or not otherwise specified (NOS) as clear cell. Medullary carcinoma of the kidney and collecting duct tumors are NOT allowed
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Up to 1 systemic line of therapy (either monotherapy or combination) including prior immunotherapy (anti-PD1, PD-L1, or CTLA-4) and multi-tyrosine kinase inhibitors in non-metastatic or metastatic setting is allowed. A washout period of 5 half lives or 21 days, whichever one is shorter, will be required for patients that have received previous systemic therapy.
- Age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) Appendix 1 performance status ≤2 (Karnofsky ≥60%).
- Patients must have adequate organ and marrow function as defined below:
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- absolute neutrophil count ≥1,000/mcL
- platelets ≥100,000/mcL
- total bilirubin ≤ institutional upper limit of normal (ULN)
- AST ≤3 × institutional ULN
- (ALT) ≤3 × institutional ULN
- creatinine ≤1.5 × institutional ULN
- eGFR ≥30 ml/min
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Patients with treated brain metastases (at least 4 weeks have passed from treatment) are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
- Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
- The effects of combination tivozanib and nivolumab on the developing human fetus are unknown. For this reason and because tyrosine kinase inhibitors and immunotherapy agents as well as other therapeutic agents used in this trial are known to be teratogenic, 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. (refer to MDA Policy CLN 1114) This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
- Postmenopausal (no menses in greater than or equal to 12 consecutive months).
- History of hysterectomy or bilateral salpingo-oophorectomy.
- Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
- History of bilateral tubal ligation or another surgical sterilization procedure. Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device, Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide.
- Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. 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 4 months after completion of combination tivozanib and nivolumab administration.
- Participants or their legally acceptable representative (LAR) must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
Who cannot join
- Prior tivozanib therapy.
- Prior nivolumab therapy.
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia.
- Patients who are receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to tivozanib or nivolumab.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 2 hours apart. Anti-hypertensives must not have been increased 30 days prior to enrollment.
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- History of autoimmune disorders except for the following:
- Patients with vitiligo or alopecia
- Hypothyroidism (e.g. following Hashimoto syndrome) that is stable on thyroid hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active autoimmune disease requiring treatment in the last 3 years may be included after consultation with study MDA lead Principal Investigator
- Active human immunodeficiency virus (HIV) infection unless patients are on effective anti-retroviral therapy with undetectable viral load within 6 months.
- Has evidence of any other medical conditions, psychiatric condition, physical examination or laboratory findings that may interfere with the planned treatment, affect subject compliance or place the subject at high risk from treatment-related complications in the opinion of the local principal investigator (PI).
- Current systemic corticosteroid use greater than prednisone 10 mg daily or equivalent.
- Pregnant women are excluded from this study because tivozanib and nivolumab are agents with the 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 tivozanib and nivolumab, breastfeeding should be discontinued if the mother is treated with tivozanib and nivolumab.
- Receiving concomitant CYP3A inducers.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United States6 sites, 6 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Irene Tsung, MD, itsung@med.umich.edu
- Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Jacob Zaemes, MD, jzaemes@bidmc.harvard.edu
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Bradley McGregor, MD, bradley_mcgregor@dfci.harvard.edu
- Recruiting
UT Southwestern Medical Center
Dallas, Texas, 75390
Hans Hammers, M.D., Ph.D., hans.hammers@utsouthwestern.edu
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Eric Jonasch, M D, 713-563-7232, ejonasch@mdanderson.org
Eric Jonasch, M D
- Recruiting
City of Hope
Irvine, California, 92618
Charles Nguyen, MD, charnguyen@coh.org
Charles Nguyen, MD
About this study
To learn if giving tivozanib in combination with nivolumab can help to control advanced nccRCC.
Read the detailed description
Primary Objectives
- To demonstrate efficacy of combination tivozanib and nivolumab in advanced non-clear cell renal cell carcinoma (nccRCC).
Secondary Objectives
- To assess the safety and toxicity of combination tivozanib and nivolumab.
- To estimate the duration of clinical efficacy
Exploratory Objectives
- To associate immune and tumor biomarkers with clinical efficacy
- Conditions
- Renal Cell Carcinoma
- Being tested
- Tivozanib, 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.
TivozanibDrug
Also called KRN 951, KRN-951, KRN951, UNII-172030934T
Given by PO
NivolumabDrug
Also called Opdivo, BMS-936558
Given by IV (vein)
| Study group | Role | What they receive |
|---|---|---|
| Combination Tivozanib and Nivolumab | Experimental | Nivolumab by vein over about 60 minutes every 4 weeks (Day 1 of each cycle). Tivozanib tablets by mouth 1 time every day for 21 days (Days 1-21 of each cycle), and then no tablets on Days 22-28 of each cycle. Receives: Drug: Tivozanib; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: through study completion; 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.
- First posted26 Sep 2023
- Study start5 Jan 2024
- Primary completion1 Nov 2028 (estimated)
- Study completion1 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- AVEO Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Eric Jonasch, M D, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06053658
- Sponsor's protocol ID
- 2022-0485
- Other IDs
- NCI-2023-07385
- Status last verified
- Oct 2026
- First submitted
- 19 Sep 2023
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Combination Tivozanib and Nivolumab in Advanced Non-Clear Cell Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT06053658
- Acronym / sponsor ID
- 2022-0485
- Conditions
- Renal Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- AVEO Pharmaceuticals, Inc.
- Study start
- 5 Jan 2024 (actual)
- Primary completion
- 1 Nov 2028 (estimated)
- Study completion
- 1 Nov 2028 (estimated)
- First posted
- 26 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To learn if giving tivozanib in combination with nivolumab can help to control advanced nccRCC.
Detailed description
Primary Objectives
- To demonstrate efficacy of combination tivozanib and nivolumab in advanced non-clear cell renal cell carcinoma (nccRCC).
Secondary Objectives
- To assess the safety and toxicity of combination tivozanib and nivolumab.
- To estimate the duration of clinical efficacy
Exploratory Objectives
- To associate immune and tumor biomarkers with clinical efficacy
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination Tivozanib and Nivolumab | Experimental | Drug: Tivozanib, Drug: NivolumabNivolumab by vein over about 60 minutes every 4 weeks (Day 1 of each cycle). Tivozanib tablets by mouth 1 time every day for 21 days (Days 1-21 of each cycle), and then no tablets on Days 22-28 of each cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Patients with histologically or cytologically confirmed metastatic non-clear cell renal cell carcinoma of papillary, chromophobe, oncocytic neoplasms, unclassified, or not otherwise specified (NOS) as clear cell. Medullary carcinoma of the kidney and collecting duct tumors are NOT allowed
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Up to 1 systemic line of therapy (either monotherapy or combination) including prior immunotherapy (anti-PD1, PD-L1, or CTLA-4) and multi-tyrosine kinase inhibitors in non-metastatic or metastatic setting is allowed. A washout period of 5 half lives or 21 days, whichever one is shorter, will be required for patients that have received previous systemic therapy.
- Age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) Appendix 1 performance status ≤2 (Karnofsky ≥60%).
Key exclusion criteria (16 listed)
- Prior tivozanib therapy.
- Prior nivolumab therapy.
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia.
- Patients who are receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to tivozanib or nivolumab.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TivozanibAlso: KRN 951, KRN-951, KRN951, UNII-172030934TGiven by PO | Drug | Combination Tivozanib and Nivolumab |
| NivolumabAlso: Opdivo, BMS-936558Given by IV (vein) | Drug | Combination Tivozanib and Nivolumab |
Primary outcome
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Time frame: through study completion; average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
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A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
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RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Eric Jonasch, M D principal investigator
M.D. Anderson Cancer Center
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tivozanib and Nivolumab in people with Renal Cell Carcinoma, run by M.D. Anderson Cancer Center at 6 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 27 inclusion and 16 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 7 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 6 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?
Contact Eric Jonasch, M D ((713) 563-7232, ejonasch@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion; average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Oct 2026.