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Clear Cell Renal Cell CarcinomaPhase 2NCT04022343

Neoadjuvant Cabozantinib in Treating Patients With Locally Advanced Kidney Cancer

A Phase 2 study testing Cabozantinib in people with Clear Cell Renal Cell Carcinoma and Renal Cell Carcinoma, run by Emory University at 1 site in United States.

Active, not recruiting

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

Official record
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Trial summary

This phase II clinical trial studies how well cabozantinib works in treating patients with kidney cancer before surgery. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cabozantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteUnited States
Study dates
6 Aug 2019to 9 Dec 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 renal mass consistent with a clinical stage ≥ T3Nx or TanyN+ or deemed unresectable by surgeon.
  • Renal cell carcinoma with clear cell component on pre-treatment biopsy of the primary tumor.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • Patients must have adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
  • Absolute neutrophil count (ANC) ≥ 1500/mm³ (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support.
  • White blood cell count ≥ 2500/mm³ (≥ 2.5 GI/L).
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  • Platelets ≥ 100,000/mm³ (≥ 100 GI/L) without transfusion.
  • Hemoglobin ≥ 9 g/dL.
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). ALP ≤ 5 x ULN with documented bone metastases.
  • Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN).
  • Serum albumin ≥ 2.8 g/dl.
  • Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min (≥ 0.67 mL/sec) using the Cockcroft-Gault equation:
  • Males: (140 - age) x weight (kg)/(serum creatinine [mg/dL] × 72)
  • Females: [(140 - age) x weight (kg)/(serum creatinine [mg/dL] × 72)] × 0.85
  • Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol).
  • No hormonal therapy, chemotherapy, immunotherapy, or any other systemic therapy for a malignancy, in the 5 years prior to current study enrollment.
  • Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, 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.
  • Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.
  • Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.

Who cannot join

  • Evidence of metastatic disease on pre-treatment imaging.
  • The subject has received of any type of cytotoxic, biologic or other systemic anticancer therapy for kidney cancer.
  • The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
  • Known brain metastases or cranial epidural disease.
  • Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
  • Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.
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  • Low-dose low molecular weight heparins (LMWH) are permitted.
  • Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
  • The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test ≥ 1.3 × the laboratory ULN within 14 days before the first dose of study treatment.
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders:
  • Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
  • Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 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 (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
  • 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, active inflammatory bowel disease (eg, 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. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.
  • Clinically significant hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose.
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
  • Other clinically significant disorders that would preclude safe study participation.
  • Serious non-healing wound/ulcer/bone fracture.
  • Uncompensated/symptomatic hypothyroidism.
  • Moderate to severe hepatic impairment (Child-Pugh B or C).
  • Major surgery (eg, 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 (eg, simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Prolongation of the QT corrected for HR using Fridericia's method (QTcF) interval defined as > 500 msec per electrocardiogram (ECG) within 28 days before first dose of study treatment. Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
  • Pregnant or lactating females.
  • Inability to swallow tablets.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations.
  • Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy. Patients with Gleason 6 (3+3) prostate cancer with previous treatment or on active surveillance may also be allowed on protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

Other trials in United States

About this study

Official title: A Phase 2 Study of Neoadjuvant Cabozantinib in Patients With Locally Advanced Non-Metastatic Clear Cell Renal Cell Carcinoma

This phase II clinical trial studies how well cabozantinib works in treating patients with kidney cancer before surgery. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the objective response rate (complete and partial responses), following the administration of cabozantinib for 12 weeks in patients with locally advanced biopsy-proven non-metastatic clear cell renal cell carcinoma (ccRCC) prior to undergoing surgery.

SECONDARY OBJECTIVES:

  1. To assess the safety, and tolerability of neoadjuvant cabozantinib.

II. To determine the clinical outcome (disease-free survival [DFS], overall survival [OS]) of patients with non-metastatic ccRCC who treated with neoadjuvant cabozantinib.

III. To evaluate the surgery related outcomes.

IV. To evaluate correlative studies, including biomarkers, quality of life, and frailty/sarcopenia assessment of patients with non-metastatic ccRCC who treated with neoadjuvant cabozantinib.

OUTLINE:

Patients receive cabozantinib orally (PO) once daily (QD) for 12 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Being tested
Cabozantinib
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, BMS-907351, XL184

    Given PO

Study groups in NCT04022343
Study groupRoleWhat they receive
Treatment (cabozantinib)ExperimentalPatients receive cabozantinib orally once daily for 12 weeks in the absence of disease progression or unacceptable toxicity. The assigned starting dose for cabozantinib is 60 mg/day. Two dose reduction levels of cabozantinib are permitted
Receives: Drug: Cabozantinib

What is being measured

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

  1. Objective Response Rate (ORR)

    Objective response rate will be evaluated using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria. All tumor measurements must be recorded in centimeters.

    For target lesions, a complete response (CR) is defined as the disappearance of all target lesions. A partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.

    Measured: At 12 weeks after cabozantinib dose

Secondary outcomes (6)

  1. Disease-free Survival (DFS)

    Disease-free survival will be defined as the interval between time of surgery and the first tumor recurrence or death. Patients will be censored at time of last follow-up. Disease-free survival will be estimated with the Kaplan-Meier method.

    Measured: From time of surgery to first tumor recurrence or death, assessed up to 3 years

  2. Overall Survival (OS)

    For overall survival, death from any cause will be defined as the event. Patients will be censored at time of last follow-up. Overall survival will be estimated with the Kaplan-Meier method.

    Measured: From time of surgery to death from any cause, assessed up to 3 years

  3. Quality of Life Assessment: Functional Assessment of Cancer Therapy-Kidney Specific Index-19 (FKSI-19) Questionnaire

    Quality of life will be studied using the Functional Assessment of Cancer Therapy-Kidney Specific Index-19 (FKSI-19) questionnaire. The questionnaire consists of 19 statements that patients answer on a 0-4 scale ("Not at all" to "Very much"). Per the instrument's official scoring guidelines, items are then reverse scored as needed and summed to create a final score ranging from 0-76, where 76 indicates the best quality of life and 0 indicates the worst.

    Measured: Baseline and weeks 6 and 12 after treatment initiation

  4. Quality of Life Assessment: Functional Assessment of Cancer Therapy-Kidney Specific Index-19 (FKSI-19) Questionnaire

    Quality of life will be studied using the Functional Assessment of Cancer Therapy-Kidney Specific Index-19 (FKSI-19) questionnaire. The questionnaire consists of 19 statements such as "I have a lack of energy" and "I have pain" which are answered on a scale of 0-4, with 0 being "Not at all" and 4 being "Very much." The scale is 0-76 (0 = worst QoL, 76 = best QoL).

    Measured: Baseline and weeks 6 and 12 after treatment initiation

  5. Frailty Assessment

    Frailty assessment will be studied using the Fried Frailty score. Domains to be assessed include shrinking, weakness, exhaustion, low activity, and slow walking speed. Scored on a total scale of 0-25 (from 5 variables, each 0-5). 0 = not frail, 25 = most frail.

    Measured: Baseline and weeks 6 and 12 after treatment initiation

  6. Sarcopenia Assessment

    Sarcopenia assessment will be done by using baseline and week 12 scans via SliceOmatic version 5.0 by TomoVision program. Cross-sectional skeletal muscle area (SMA) at the L3 vertebra will be segmented to calculate the Skeletal Muscle Index (SMI = SMA cm² / height m²). Sarcopenia is defined as an SMI at or below the 25th percentile of age- and sex-specific reference values from the Fintelmann et al. (2024) Framingham Heart Study cohort.

    Measured: Baseline and week 12 after treatment initiation

Timeline

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

  1. First posted17 Jul 2019
  2. Study start6 Aug 2019
  3. Primary completion2 Feb 2022
  4. Study completion9 Dec 2026 (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
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04022343
Sponsor's protocol ID
IRB00110583
Other IDs
NCI-2019-02253, Winship4643-19, P30CA138292
Status last verified
Apr 2026
First submitted
15 Jul 2019
Last updated
5 May 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bilen MA, Vo BT, Liu Y, Greenwald R, Davarpanah AH, McGuire D, Shiradkar R, Li L, Nazha B, Brown JT, Williams S, Session W, Russler G, Caulfield S, Joshi SS, Narayan VM, Filson CP, Ogan K, Kucuk O, Carthon BC, Del Balzo L, Cohen A, Boyanton A, Prokhnevska N, Cardenas MA, Sobierajska E, Jansen CS, Patil DH, Nicaise E, Osunkoya AO, Kissick H, Master VA. Neoadjuvant cabozantinib restores CD8+ T cells in patients with locally advanced non-metastatic clear cell renal cell carcinoma: a phase 2 trial. Res Sq [Preprint]. 2024 Aug 8:rs.3.rs-4849400. doi: 10.21203/rs.3.rs-4849400/v1.

    PubMed 39149474

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib in people with Clear Cell Renal Cell Carcinoma and Renal Cell Carcinoma, run by Emory University 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 19 inclusion and 29 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 May 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?

Yes. Results are posted in the registry (first posted 13 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Response Rate (ORR) (time frame: At 12 weeks after cabozantinib dose). 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 NCT04022343, which also lists 1 linked publication.

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 May 2026.

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