Metastatic Renal Cell CarcinomaPhase 2NCT05263050
Trial of an Alternative Cabozantinib Dosing Schedule in Metastatic Renal Cell Carcinoma and Neuroendocrine Tumors
A Phase 2 study testing Cabozantinib and Nivolumab in people with Metastatic Renal Cell Carcinoma and Clear-cell Metastatic Renal Cell Carcinoma, run by Fox Chase Cancer Center at 1 site in United States.
Trial summary
This is a multi-site, three-cohort phase II trial of cabozantinib for IMDC all-risk frontline metastatic renal cell carcinoma (mRCC) patients OR any line mRCC patients who have not previously been treated with cabozantinib, and patients with pancreatic or extra-pancreatic neuroendocrine tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Renal Cell Carcinoma, Clear-cell Metastatic Renal Cell Carcinoma, Neuroendocrine Tumors
- What is being tested?
- Cabozantinib and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 111 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jan 2022to Feb 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
- Cohorts A and B: Histologically or cytologically confirmed advanced RCC with any clear cell or non-clear cell component. 100% sarcomatoid is permissible.
- Cohorts A and B: Patient may have had any number of prior therapies for Cohort A, but for Cohort B patients must not have received any systemic therapy in the metastatic setting
- Patients who have received prior (neo)adjuvant immunotherapy with pembrolizumab or similar are eligible for Cohort B IF they completed the adjuvant therapy \> 12 months from start of trial therapy
- Treatment naïve patients may be treated in Cohort A if deemed not candidates for nivolumab or if felt single agent cabozantinib most appropriate by the treating clinician
- Cohort C: Well differentiated NET, grades 1-3 (any primary site) who have progressed on or are not eligible for somatostatin analogs per treating physician discretion
- Cohort C: Disease progression within prior 12 months
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- Cohort C: Prior or concurrent treatment with somatostatin analogue allowed but no limit on lines of therapy (stable dose of somatostatin for 2 months)
- All Cohorts:
- At least one measurable lesion as defined by RECIST version 1.1
- No evidence of pre-existing uncontrolled hypertension as assessed by investigator. Patients may undergo adjustments or additions to their antihypertensive regimen before or during screening to achieve optimal BP control.
- Age \> 18 years.
- ECOG performance status 0 - 2
- Patients must have normal organ and marrow function as defined below
- Leukocytes, \> 2,000/mcL
- Absolute neutrophil count, \> 1,500/mcL
- Platelets, \> 100,000/mcL
- Hgb, \> 9 g/dL (\>90 g/L)
- Total bilirubin, ≤ 1.5 x ULN (with the exception of of individuals with Gilberts syndrome who may have a bilirubin \<3.0 mg/dL)
- AST/ALT (SGOT/SGPT)/ALP, \< 3 x ULN ALP ≤ 5x ULN with documented bone metastases.
- Albumin, \> 2.8 g/dL
- Creatinine clearance, \> 30 Ml/min/1.73 m2 for patients with creatinine levels above institutional normal
- PT/INR or PTT, \< 1.3 x the laboratory ULN
- Ability to understand and willingness to sign a written informed consent and HIPAA consent document
- Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment
Who cannot join
- Patients who have had systemic anti-cancer therapy or radiotherapy within 14 days or five half-lives, whichever is shorter, prior to entering the study.
- Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks, or systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Ongoing clinically relevant complications from prior radiation therapy would preclude eligibility.
- Patients with prior therapy with cabozantinib.
- Prior systemic therapy directed at advanced RCC is not allowed for patients enrolled to Cohort B (treatment-naïve group).
- Cohort B only: Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
- Cohort B only: Patients have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
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- Patients may not be receiving any other investigational agents
- History of allergic reactions or hypersensitivity attributed to compound of similar chemical or biologic composition to the agent(s) used in this study
- Current use or anticipated need for treatment with drugs or foods that are known strong CYP3A4 inhibitors and inducers. Refer to Section 5.3.2 for detailed information. The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed.
- Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
- Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
- Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Cardiovascular disorders:
- Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
- QTcF \> 500 msec within 28 days before first dose of study treatment.
- Uncontrolled hypertension defined as sustained blood pressure (BP) \> 160 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment.
- Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
- Subjects with a diagnosis of incidental, sub-segmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion #6) for at least 1 week before first dose of study treatment.
- Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
- The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
- Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.
- Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
- Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
- Lesions invading or encasing any major blood vessels. Subjects with lesions invading the intrahepatic vasculature, including portal vein, hepatic vein, and hepatic artery, are eligible.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Matthew Zibelman, MD, 888-369-2427
About this study
Official title: GU-187: Phase II Trial of Alternative Cabozantinib Dosing Schedule in Metastatic Renal Cell Carcinoma and Neuroendocrine Tumors
This is a multi-site, three-cohort phase II trial of cabozantinib for IMDC all-risk frontline metastatic renal cell carcinoma (mRCC) patients OR any line mRCC patients who have not previously been treated with cabozantinib, and patients with pancreatic or extra-pancreatic neuroendocrine tumors.
Read the detailed description
This is a multi-site, three-cohort phase II trial of cabozantinib for IMDC all-risk frontline metastatic renal cell carcinoma (mRCC) patients OR any line mRCC patients who have not previously been treated with cabozantinib, and patients with pancreatic or extra-pancreatic neuroendocrine tumors (NETs). The study is comprised of three cohorts; Cohorts A and C will employ the alternative dosing schema with cabozantinib monotherapy in any-line clear cell or non-clear cell mRCC patients and patients with pancreatic or extra-pancreatic NETs, and Cohort B will employ the alternative dosing schema with cabozantinib in combination with standard-dosed nivolumab in front-line clear cell or non-clear cell mRCC patients.
Study will accrue a total of 111 patients (Cohort A n=49, Cohort B n=37, Cohort C n=25). Patients in cohorts A and C will be treated with the same cabozantinib alternative dosing schema and schedule, with the exception of Cohort B patients also receiving monthly fix-dosed nivolumab infusions. Patients will start at 40 mg of cabozantinib daily and dose escalate or de-escalate based on pre-specified criteria and at set dosing schedules to allow for smaller median dose changes between adjustments. The de-escalation would be fine-tuned and adjustments would be made in 10 mg average daily dosing increments by utilizing alternate day dosing schedules (e.g. 60 mg/40 mg every other day) rather than decreasing by 20 mg (table 1). The maximum dose of cabozantinib is 60 mg daily, while the lowest dosing level on trial will be 20 mg every other day. Cycles would be 28 days, with weekly follow-up for cycle 1 and bi-weekly follow-up for cycle 2 to allow for prompt dose adjustments, and then monthly. At each check-in, patients in Cohorts A and B that have met the established protocol criteria (outlined in Section 6.3) and were not yet at the maximum dose of 60 mg daily would be eligible for dose-escalation. At each check in, patients in cohort C that have met the established protocol criteria and were not yet at the maximum dose of 60 mg daily will be mandated to start next higher dose level. Patients would also be dose de-escalated as determined by the investigator. Patients who de-escalate may be allowed to re-escalate in the future.
- Conditions
- Metastatic Renal Cell Carcinoma, Clear-cell Metastatic Renal Cell Carcinoma, Neuroendocrine Tumors, Carcinoid Tumor
- Being tested
- Cabozantinib, Nivolumab
- Medical subject headings
- Carcinoma, Renal Cell, Clear-cell metastatic renal cell carcinoma, Neuroendocrine Tumors, Carcinoid Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Also called XL184
Cabozantinib initiated at 40 mg daily. Dose-escalate or de-escalate based on pre-specified criteria and at set dosing schedules
NivolumabDrug
Also called Opdivo
Nivolumab injection is to be administered as an IV infusion at a dose of 480 mg on day 1 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| Cabozantinib | Experimental | Cabozantinib treatment will start at 40 mg of cabozantinib daily and dose escalate or de-escalate based on pre-specified criteria and at set dosing schedules to allow for smaller median dose changes between adjustments. The de-escalation would be fine-tuned and adjustments would be made in 10 mg average daily dosing increments by utilizing alternate day dosing schedules (e.g 60 mg/40 mg every other day) rather than decreasing by 20 mg. The maximum dose of cabozantinib is 60 mg daily. Cycles would be 28 days, with weekly follow-up for cycle 1 and bi-weekly follow-up for cycle 2 to allow for prompt dose adjustments, and then monthly. At each check-in, patients that have met the established protocol criteria and were not yet at the maximum dose of 60 mg daily would be eligible for dose-escalation. Patients would also be dose de-escalated as determined by the investigator. Patients who de-escalate may be allowed to re-escalate in the future. Receives: Drug: Cabozantinib |
| Cabozantinib and nivolumab | Experimental | Cabozantinib treatment will receive monthly fix-dosed nivolumab infusions, and start at 40 mg of cabozantinib daily and dose escalate or de-escalate based on pre-specified criteria and at set dosing schedules to allow for smaller median dose changes between adjustments. The de-escalation would be fine-tuned and adjustments would be made in 10 mg average daily dosing increments by utilizing alternate day dosing schedules (e.g 60 mg/40 mg every other day) rather than decreasing by 20 mg. The maximum dose of cabozantinib is 60 mg daily. Cycles would be 28 days, with weekly follow-up for cycle 1 and bi-weekly follow-up for cycle 2 to allow for prompt dose adjustments, and then monthly. At each check-in, patients that have met established protocol criteria and were not yet at the maximum dose of 60 mg daily would be eligible for dose-escalation. Patients would also be dose de-escalated as determined by the investigator. Patients who de-escalate may be allowed to re-escalate in the future. Receives: Drug: Cabozantinib; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cohort A: Average daily dose of cabozantinib > 42.8 mg in at least 70% of patients
To show that alternative cabozantinib dosing can improve average daily dose compared to historical controls
Measured: 2 years
Cohort B: 75% of patients alive and progression free at 12 months
Cohort B: To show that alternative cabozantinib dosing + nivolumab (standard dose) can improve 12-month rate of progression-free survival over standard dose cabozantinib + nivolumab
Measured: 1 year
Cohort C: Decreased rate of grade ≥ 3 adverse events compared to 75% reported in CABINET trial
Cohort C: To show that alternative cabozantinib dosing can improve rates of grade > 3 adverse events compared to the grade 3-5 adverse events reported in the CABINET trial
Measured: 2 years
Secondary outcomes (10)
Cohort A: Decreased grade ≥ 3 adverse events compared to historical controls (METEOR trial)
Demonstrate that alternative dosing can change overall toxicity compared to historical controls by monitoring grade ≥ 3 adverse events compared to historical controls
Measured: 2 years
Cohort A: Improved median duration of time on drug compared to historical controls
Show that alternative scheduling can change median duration of time on drug compared to historical controls
Measured: 2 years
Cohort A: Objective response rate per RECIST 1.1 criteria of all patients treated
Response rates will be summarized via frequencies and 95% confidence intervals, and compared to historical results using two-sided one-sample exact binomial tests of proportions
Measured: 2 years
Cohort B: Decreased grade ≥ 3 adverse events compared to historical comparison from the CheckMate 9ER trial
Demonstrate that alternative dosing can change overall toxicity compared to historical controls by monitoring grade ≥ 3 adverse events compared to historical controls
Measured: 2 years
Cohort B: Improved median duration on the drug (as defined by time from initiation of therapy to time of cessation of therapy) compared to historical comparison to the CheckMate 9ER trial
Show that alternative scheduling can change median duration of time on drug compared to historical controls
Measured: 2 years
Cohort B: Increased median average daily dose of cabozantinib
Calculate the median average daily dose, and compare it to the null hypothesis using a one-sample Wilcoxon signed-ran test
Measured: 2 years
Cohort B: Objective response rate per RECIST 1.1 criteria of all patients treated
Response rates will be summarized via frequencies and 95% confidence intervals, and compared to historical results using two-sided one-sample exact binomial tests of proportions
Measured: 2 years
Cohort B: Overall Survival analysis of all patients treated within the cohort
Overall survival will be analyzed and summarized using Kaplan-Meier methods and compared to results of historic control using two-sided one-sample log-rank tests
Measured: 2 years
Cohort C: Percent of patients requiring dose reduction as a descriptive endpoint
Percent of patients requiring dose reduction as a descriptive endpoint will be calculated along with the 95% confidence interval.
Measured: 2 years
Cohort C: Progression free survival as a descriptive endpoint
Progression free survival will be characterized as a descriptive endpoint using a Kaplan-Meier curve.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2022
- Study start21 Jan 2022
- Primary completionDec 2026 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Fox Chase 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Patients will start at 40 mg of cabozantinib daily and dose escalate or de-escalate based on pre-specified criteria and at set dosing schedules to allow for smaller median dose changes between adjustments. Patients in cohorts A and C will be treated with the same cabozantinib alternative dosing schema and schedule, with the exception of Cohort B patients also receiving monthly fix-dosed nivolumab infusions.
- Masking
- None (open label)
- Enrolment
- 111 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Exelixis
- Responsible party
- Sponsor
- Investigators
- Matthew Zibelman, MD, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05263050
- Sponsor's protocol ID
- 21-1020
- Other IDs
- GU-187
- Status last verified
- Jul 2026
- First submitted
- 21 Feb 2022
- Last updated
- 28 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GU-187: Phase II Trial of Alternative Cabozantinib Dosing Schedule in Metastatic Renal Cell Carcinoma and Neuroendocrine Tumors
- ClinicalTrials.gov ID
- NCT05263050
- Acronym / sponsor ID
- 21-1020
- Conditions
- Metastatic Renal Cell Carcinoma, Clear-cell Metastatic Renal Cell Carcinoma, Neuroendocrine Tumors, Carcinoid Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 111 participants (estimated)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Collaborators
- Exelixis
- Study start
- 21 Jan 2022 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 2 Mar 2022 (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.
This is a multi-site, three-cohort phase II trial of cabozantinib for IMDC all-risk frontline metastatic renal cell carcinoma (mRCC) patients OR any line mRCC patients who have not previously been treated with cabozantinib, and patients with pancreatic or extra-pancreatic neuroendocrine tumors.
Detailed description
This is a multi-site, three-cohort phase II trial of cabozantinib for IMDC all-risk frontline metastatic renal cell carcinoma (mRCC) patients OR any line mRCC patients who have not previously been treated with cabozantinib, and patients with pancreatic or extra-pancreatic neuroendocrine tumors (NETs). The study is comprised of three cohorts; Cohorts A and C will employ the alternative dosing schema with cabozantinib monotherapy in any-line clear cell or non-clear cell mRCC patients and patients with pancreatic or extra-pancreatic NETs, and Cohort B will employ the alternative dosing schema with cabozantinib in combination with standard-dosed nivolumab in front-line clear cell or non-clear cell mRCC patients.
Study will accrue a total of 111 patients (Cohort A n=49, Cohort B n=37, Cohort C n=25). Patients in cohorts A and C will be treated with the same cabozantinib alternative dosing schema and schedule, with the exception of Cohort B patients also receiving monthly fix-dosed nivolumab infusions. Patients will start at 40 mg of cabozantinib daily and dose escalate or de-escalate based on pre-specified criteria and at set dosing schedules to allow for smaller median dose changes between adjustments. The de-escalation would be fine-tuned and adjustments would be made in 10 mg average daily dosing increments by utilizing alternate day dosing schedules (e.g. 60 mg/40 mg every other day) rather than decreasing by 20 mg (table 1). The maximum dose of cabozantinib is 60 mg daily, while the lowest dosing level on trial will be 20 mg every other day. Cycles would be 28 days, with weekly follow-up for cycle 1 and bi-weekly follow-up for cycle 2 to allow for prompt dose adjustments, and then monthly. At each check-in, patients in Cohorts A and B that have met the established protocol criteria (outlined in Section 6.3) and were not yet at the maximum dose of 60 mg daily would be eligible for dose-escalation. At each check in, patients in cohort C that have met the established protocol criteria and were not yet at the maximum dose of 60 mg daily will be mandated to start next higher dose level. Patients would also be dose de-escalated as determined by the investigator. Patients who de-escalate may be allowed to re-escalate in the future.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will start at 40 mg of cabozantinib daily and dose escalate or de-escalate based on pre-specified criteria and at set dosing schedules to allow for smaller median dose changes between adjustments. Patients in cohorts A and C will be treated with the same cabozantinib alternative dosing schema and schedule, with the exception of Cohort B patients also receiving monthly fix-dosed nivolumab infusions.
| Arm | Type | Receives |
|---|---|---|
| Cabozantinib | Experimental | Drug: CabozantinibCabozantinib treatment will start at 40 mg of cabozantinib daily and dose escalate or de-escalate based on pre-specified criteria and at set dosing schedules to allow for smaller median dose changes between adjustments. The de-escalation would be fine-tuned and adjustments would be made in 10 mg average daily dosing increments by utilizing alternate day dosing schedules (e.g 60 mg/40 mg every other day) rather than decreasing by 20 mg. The maximum dose of cabozantinib is 60 mg daily. Cycles would be 28 days, with weekly follow-up for cycle 1 and bi-weekly follow-up for cycle 2 to allow for prompt dose adjustments, and then monthly. At each check-in, patients that have met the established protocol criteria and were not yet at the maximum dose of 60 mg daily would be eligible for dose-escalation. Patients would also be dose de-escalated as determined by the investigator. Patients who de-escalate may be allowed to re-escalate in the future. |
| Cabozantinib and nivolumab | Experimental | Drug: Cabozantinib, Drug: NivolumabCabozantinib treatment will receive monthly fix-dosed nivolumab infusions, and start at 40 mg of cabozantinib daily and dose escalate or de-escalate based on pre-specified criteria and at set dosing schedules to allow for smaller median dose changes between adjustments. The de-escalation would be fine-tuned and adjustments would be made in 10 mg average daily dosing increments by utilizing alternate day dosing schedules (e.g 60 mg/40 mg every other day) rather than decreasing by 20 mg. The maximum dose of cabozantinib is 60 mg daily. Cycles would be 28 days, with weekly follow-up for cycle 1 and bi-weekly follow-up for cycle 2 to allow for prompt dose adjustments, and then monthly. At each check-in, patients that have met established protocol criteria and were not yet at the maximum dose of 60 mg daily would be eligible for dose-escalation. Patients would also be dose de-escalated as determined by the investigator. Patients who de-escalate may be allowed to re-escalate in the future. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Cohorts A and B: Histologically or cytologically confirmed advanced RCC with any clear cell or non-clear cell component. 100% sarcomatoid is permissible.
- Cohorts A and B: Patient may have had any number of prior therapies for Cohort A, but for Cohort B patients must not have received any systemic therapy in the metastatic setting
- Patients who have received prior (neo)adjuvant immunotherapy with pembrolizumab or similar are eligible for Cohort B IF they completed the adjuvant therapy \> 12 months from start of trial therapy
- Treatment naïve patients may be treated in Cohort A if deemed not candidates for nivolumab or if felt single agent cabozantinib most appropriate by the treating clinician
- Cohort C: Well differentiated NET, grades 1-3 (any primary site) who have progressed on or are not eligible for somatostatin analogs per treating physician discretion
Key exclusion criteria (25 listed)
- Patients who have had systemic anti-cancer therapy or radiotherapy within 14 days or five half-lives, whichever is shorter, prior to entering the study.
- Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks, or systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Ongoing clinically relevant complications from prior radiation therapy would preclude eligibility.
- Patients with prior therapy with cabozantinib.
- Prior systemic therapy directed at advanced RCC is not allowed for patients enrolled to Cohort B (treatment-naïve group).
- Cohort B only: Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
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: XL184Cabozantinib initiated at 40 mg daily. Dose-escalate or de-escalate based on pre-specified criteria and at set dosing schedules | Drug | Cabozantinib, Cabozantinib and nivolumab |
| NivolumabAlso: OpdivoNivolumab injection is to be administered as an IV infusion at a dose of 480 mg on day 1 of each cycle | Drug | Cabozantinib and nivolumab |
Primary outcome
Cohort A: Average daily dose of cabozantinib > 42.8 mg in at least 70% of patients
Time frame: 2 years
To show that alternative cabozantinib dosing can improve average daily dose compared to historical controls
Cohort B: 75% of patients alive and progression free at 12 months
Time frame: 1 year
Cohort B: To show that alternative cabozantinib dosing + nivolumab (standard dose) can improve 12-month rate of progression-free survival over standard dose cabozantinib + nivolumab
Cohort C: Decreased rate of grade ≥ 3 adverse events compared to 75% reported in CABINET trial
Time frame: 2 years
Cohort C: To show that alternative cabozantinib dosing can improve rates of grade > 3 adverse events compared to the grade 3-5 adverse events reported in the CABINET trial
10 secondary outcomes
Cohort A: Decreased grade ≥ 3 adverse events compared to historical controls (METEOR trial)
Time frame: 2 years
Cohort A: Improved median duration of time on drug compared to historical controls
Time frame: 2 years
Cohort A: Objective response rate per RECIST 1.1 criteria of all patients treated
Time frame: 2 years
Cohort B: Decreased grade ≥ 3 adverse events compared to historical comparison from the CheckMate 9ER trial
Time frame: 2 years
Cohort B: Improved median duration on the drug (as defined by time from initiation of therapy to time of cessation of therapy) compared to historical comparison to the CheckMate 9ER trial
Time frame: 2 years
Cohort B: Increased median average daily dose of cabozantinib
Time frame: 2 years
Cohort B: Objective response rate per RECIST 1.1 criteria of all patients treated
Time frame: 2 years
Cohort B: Overall Survival analysis of all patients treated within the cohort
Time frame: 2 years
Cohort C: Percent of patients requiring dose reduction as a descriptive endpoint
Time frame: 2 years
Cohort C: Progression free survival as a descriptive endpoint
Time frame: 2 years
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 28 Jul 2026.
- Individual participant dataSharing planned: No
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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.
Matthew Zibelman, MD principal investigator
Fox Chase Cancer Center
1 site 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 and Nivolumab in people with Metastatic Renal Cell Carcinoma and Clear-cell Metastatic Renal Cell Carcinoma, run by Fox Chase 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 24 inclusion and 25 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 28 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 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 Ryan Romasko (888-369-2427, ryan.romasko@fccc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cohort A: Average daily dose of cabozantinib > 42.8 mg in at least 70% of patients (time frame: 2 years). 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?
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 28 Jul 2026.