Kidney CancerPhase 2Cyto-KIKNCT04322955
CYTO Reductive Surgery in Kidney Cancer Plus Immunotherapy and Targeted Kinase Inhibition
A Phase 2 study testing Cabozantinib, Nivolumab and Cytoreductive nephrectomy in people with Kidney Cancer and Renal Cell Carcinoma, run by Mark Stein at 4 sites in United States.
Trial summary
The purpose of this study is to determine if the use of immunotherapy nivolumab and the targeted therapy cabozantinib prior to removal of the kidney, will increase the number subjects who are without any visible kidney cancer in their body at some point during the course of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Cancer, Renal Cell Carcinoma
- What is being tested?
- Cabozantinib, Nivolumab and Cytoreductive nephrectomy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 4 sitesUnited States
- Study dates
- 22 Jun 2020to Feb 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
- Written informed consent and HIPAA authorization for release of personal health information.
- Age ≥ 18years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 28 days prior to registration.
- Radiographically consistent with metastatic renal cell carcinoma (with subsequent pathologic confirmation of renal cell carcinoma with a clear cell component) OR histological/ cytological evidence of metastatic renal cell carcinoma with a clear cell component
- Measurable tumor in the kidney according to RECIST 1.1
- No prior therapy for metastatic renal cell carcinoma
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- Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 14 days prior to registration.
- Females of childbearing potential must have a negative serum pregnancy test during screening, within 14 days of Cycle 1 Day 1. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
- Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
Who cannot join
- Patients who had previously undergone nephrectomy for renal cancer are excluded
- Uncontrolled bleeding, hypertension, or cardiovascular disease.
- Prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4 inhibitors
- The subject has active brain metastases or epidural disease
- Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment.
- The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test ≥1.3 x the laboratory upper limit of normal (ULN)
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- The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, thrombin or Factor Xa inhibitors. Aspirin (up to 325 mg/day), low-dose warfarin (≤1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
- Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
- Hemoptysis of ≥0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment
- Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
- The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
- Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment
- Patients are excluded if they have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study start
- Cardiovascular disorders including:
- Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening
- Concurrent uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 14 days of the first dose of study treatment.
- The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) >500 ms within 28 days before registration.
- Severe active infection requiring systemic treatment within 28 days before the first dose of study treatment
- Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
- Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (e.g., simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
- History of organ transplant
- Concurrent uncompensated hypothyroidism
- Unable to swallow tablets
- Active infection requiring systemic therapy
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least 2 years.
- Active central nervous system (CNS) metastases
- Treatment with any investigational drug within 28 days prior to registration.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Cleveland Clinic
Cleveland, Ohio, 44012
Ohio State University Wexner Medical Center
Columbus, Ohio, 43221
The Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: Cyto-KIK; TRIAL (CYTO Reductive Surgery in Kidney Cancer Plus Immunotherapy (Nivolumab) and Targeted Kinase Inhibition (Cabozantinib)
The purpose of this study is to determine if the use of immunotherapy nivolumab and the targeted therapy cabozantinib prior to removal of the kidney, will increase the number subjects who are without any visible kidney cancer in their body at some point during the course of treatment.
Read the detailed description
People with metastatic kidney cancer are usually treated with medications to slow the growth of the cancer. In addition, people who still have the kidney where the cancer started may have the kidney removed during the course of treatment. This surgery is done in order to decrease the amount of tumor in the body. This surgery is referred to as a cytoreductive nephrectomy. In the current study, nivolumab, an immune checkpoint inhibitor, is being administered in combination with cabozantinib, a targeted therapy. The combination of nivolumab and cabozantinib is FDA approved for the treatment of metastatic kidney cancer. In this study, treatment consists of cabozantinib and nivolumab plus a cytoreductive nephrectomy. Eligible subjects, who have not received prior therapy for metastatic clear cell renal cell carcinoma, are treated with cabozantinib and nivolumab for approximately 3 months prior to undergoing cytoreductive nephrectomy. After nephrectomy, patients who are benefiting from treatment may resume cabozantinib and nivolumab. This study will help investigators to understand the immune effects of cabozantinib and nivoluamb in the kidney tumor and will provide information on the potential clinical benefit associated with cytoreductive nephrectomy in combination with cabozanitnib and nivolumab.
- Conditions
- Kidney Cancer, Renal Cell Carcinoma
- Being tested
- Cabozantinib, Nivolumab, Cytoreductive nephrectomy
- Medical subject headings
- Kidney Neoplasms, 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 XL184
2 x 20 mg capsules taken orally daily
NivolumabDrug
Also called BMS-936558
480mg IV on first day of each 28-day cycle
Cytoreductive nephrectomyProcedure or surgery
Surgery removing as much tumor tissue as possible, possibly including surrounding tissues.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with cabozantinib and nivolumab with nephrectomy | Experimental | All study participants will receive the same study medications, cabozantinib and nivolumab. The study drug, nivolumab, will be administered through an IV infusion every 4 weeks and cabozantinib will be administered orally daily. Initially participants will receive study treatment for 12 weeks. The cabozantinib will then be stopped prior to the nephrectomy. Initially patients enrolled on the study will be assigned to cohort 1.
Patients who are assigned to cohort 1 will be treated with cabozantinib until 21 days prior to surgery. A patient in cohort 1 will be evaluable for assessment of the cabozantinib washout interval ("evaluable patients") if they
1. complete at least 10 of the 14 scheduled cabozantinib doses in the two week period prior to stopping cabozantinib AND
2. have surgical resection of the primary tumor.
In cohort 2, subjects will receive cabozantinib until 14 days prior to nephrectomy. Receives: Drug: Cabozantinib; Drug: Nivolumab; Procedure: Cytoreductive nephrectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with a Complete Response
The percentage of participants with a complete response following treatment. Complete response 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.
Measured: Up to 5 years after completion of treatment
Secondary outcomes (5)
Median Size Reduction of the Primary Tumor
Median size reduction of the primary tumor after treatment for 12 weeks prior to nephrectomy will be determined using RECIST 1.1 criteria applied to the primary tumor.
Measured: 12 weeks
Progression Free Survival (PFS)
PFS is defined as the time from the time of first treatment on study until disease's progression or death as a result of any cause.
Measured: Up to 5 years after completion of treatment
Response Rate
Response rate will include confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST1.1.
Measured: Up to 5 years after completion of treatment
Overall Survival
Overall survival will be measured from the time of first treatment on study until death or last follow-up.
Measured: Up to 5 years after completion of treatment
Surgical Outcomes
Surgical outcomes will be assessed by the Clavien-Dindo classification system, which ranks the severity of surgical complications. The scale consists of several grades (Grade I, II, IIIa, IIIb, IVa, IVb and V) from Grade I being of low severity outcome to Grade V being highest and worst outcome.
Measured: Up to 5 years after completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2020
- Study start22 Jun 2020
- Primary completionMay 2027 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney CancerStudies of the same condition, open and under way.
- 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
- Sequential
- Model description
- Initially patients enrolled on the study will be assigned to Cohort 1. Patients assigned to Cohort 1 will have the cabozantinib held for three weeks prior to removal of the kidney. A patient in cohort 1 will be evaluable for assessment of the cabozantinib washout interval ("evaluable patients") if they 1. complete at least 10 of the 14 scheduled cabozantinib doses in the two week period prior to stopping cabozantinib AND 2. have surgical resection of the primary tumor. In cohort 2, subjects will receive cabozantinib until 14 days prior to nephrectomy.
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mark Stein
- Sponsor type
- University, hospital or other
- Collaborators
- Exelixis, Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Mark Stein, Columbia University
- Investigators
- Mark N Stein, MD, Principal investigator, Associate Professor of Medicine Division of Hematology/Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04322955
- Sponsor's protocol ID
- AAAS6927
- Acronym
- Cyto-KIK
- Status last verified
- Jun 2026
- First submitted
- 10 Feb 2020
- Last updated
- 5 Jun 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 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cyto-KIK; TRIAL (CYTO Reductive Surgery in Kidney Cancer Plus Immunotherapy (Nivolumab) and Targeted Kinase Inhibition (Cabozantinib)
- ClinicalTrials.gov ID
- NCT04322955
- Acronym / sponsor ID
- Cyto-KIK / AAAS6927
- Conditions
- Kidney Cancer, Renal Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Mark SteinUniversity, hospital or other
- Collaborators
- Exelixis, Bristol-Myers Squibb
- Study start
- 22 Jun 2020 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- Feb 2028 (estimated)
- First posted
- 26 Mar 2020 (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.
The purpose of this study is to determine if the use of immunotherapy nivolumab and the targeted therapy cabozantinib prior to removal of the kidney, will increase the number subjects who are without any visible kidney cancer in their body at some point during the course of treatment.
Detailed description
People with metastatic kidney cancer are usually treated with medications to slow the growth of the cancer. In addition, people who still have the kidney where the cancer started may have the kidney removed during the course of treatment. This surgery is done in order to decrease the amount of tumor in the body. This surgery is referred to as a cytoreductive nephrectomy. In the current study, nivolumab, an immune checkpoint inhibitor, is being administered in combination with cabozantinib, a targeted therapy. The combination of nivolumab and cabozantinib is FDA approved for the treatment of metastatic kidney cancer. In this study, treatment consists of cabozantinib and nivolumab plus a cytoreductive nephrectomy. Eligible subjects, who have not received prior therapy for metastatic clear cell renal cell carcinoma, are treated with cabozantinib and nivolumab for approximately 3 months prior to undergoing cytoreductive nephrectomy. After nephrectomy, patients who are benefiting from treatment may resume cabozantinib and nivolumab. This study will help investigators to understand the immune effects of cabozantinib and nivoluamb in the kidney tumor and will provide information on the potential clinical benefit associated with cytoreductive nephrectomy in combination with cabozanitnib and nivolumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Initially patients enrolled on the study will be assigned to Cohort 1. Patients assigned to Cohort 1 will have the cabozantinib held for three weeks prior to removal of the kidney. A patient in cohort 1 will be evaluable for assessment of the cabozantinib washout interval ("evaluable patients") if they 1. complete at least 10 of the 14 scheduled cabozantinib doses in the two week period prior to stopping cabozantinib AND 2. have surgical resection of the primary tumor. In cohort 2, subjects will receive cabozantinib until 14 days prior to nephrectomy.
| Arm | Type | Receives |
|---|---|---|
| Treatment with cabozantinib and nivolumab with nephrectomy | Experimental | Drug: Cabozantinib, Drug: Nivolumab, Procedure: Cytoreductive nephrectomyAll study participants will receive the same study medications, cabozantinib and nivolumab. The study drug, nivolumab, will be administered through an IV infusion every 4 weeks and cabozantinib will be administered orally daily. Initially participants will receive study treatment for 12 weeks. The cabozantinib will then be stopped prior to the nephrectomy. Initially patients enrolled on the study will be assigned to cohort 1. Patients who are assigned to cohort 1 will be treated with cabozantinib until 21 days prior to surgery. A patient in cohort 1 will be evaluable for assessment of the cabozantinib washout interval ("evaluable patients") if they 1. complete at least 10 of the 14 scheduled cabozantinib doses in the two week period prior to stopping cabozantinib AND 2. have surgical resection of the primary tumor. In cohort 2, subjects will receive cabozantinib until 14 days prior to nephrectomy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Written informed consent and HIPAA authorization for release of personal health information.
- Age ≥ 18years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 28 days prior to registration.
- Radiographically consistent with metastatic renal cell carcinoma (with subsequent pathologic confirmation of renal cell carcinoma with a clear cell component) OR histological/ cytological evidence of metastatic renal cell carcinoma with a clear cell component
- Measurable tumor in the kidney according to RECIST 1.1
Key exclusion criteria (28 listed)
- Patients who had previously undergone nephrectomy for renal cancer are excluded
- Uncontrolled bleeding, hypertension, or cardiovascular disease.
- Prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4 inhibitors
- The subject has active brain metastases or epidural disease
- Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment.
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 |
|---|---|---|
| CabozantinibAlso: XL1842 x 20 mg capsules taken orally daily | Drug | Treatment with cabozantinib and nivolumab with nephrectomy |
| NivolumabAlso: BMS-936558480mg IV on first day of each 28-day cycle | Drug | Treatment with cabozantinib and nivolumab with nephrectomy |
| Cytoreductive nephrectomySurgery removing as much tumor tissue as possible, possibly including surrounding tissues. | Procedure or surgery | Treatment with cabozantinib and nivolumab with nephrectomy |
Primary outcome
Percentage of Participants with a Complete Response
Time frame: Up to 5 years after completion of treatment
The percentage of participants with a complete response following treatment. Complete response 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.
5 secondary outcomes
Median Size Reduction of the Primary Tumor
Time frame: 12 weeks
Progression Free Survival (PFS)
Time frame: Up to 5 years after completion of treatment
Response Rate
Time frame: Up to 5 years after completion of treatment
Overall Survival
Time frame: Up to 5 years after completion of treatment
Surgical Outcomes
Time frame: Up to 5 years after completion of treatment
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 5 Jun 2026.
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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. This study is not recruiting at the moment.
Mark N Stein, MD principal investigator
Associate Professor of Medicine Division of Hematology/Oncology
4 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 Cabozantinib, Nivolumab and Cytoreductive nephrectomy in people with Kidney Cancer and Renal Cell Carcinoma, run by Mark Stein 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 10 inclusion and 28 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 5 Jun 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?
Percentage of Participants with a Complete Response (time frame: Up to 5 years after completion of treatment). 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 5 Jun 2026.