Neoadjuvant Cabozantinib in Treating Patients With Locally Advanced Kidney Cancer

NCT04022343 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB00110583NCI-2019-02253Winship4643-19P30CA138292
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Stage III Renal Cell Cancer AJCC v8; Clear Cell Renal Cell Carcinoma; Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (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.

  At 12 weeks after cabozantinib dose

Secondary Outcomes (6)

• Disease-free Survival (DFS)

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

• Overall Survival (OS)

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

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

  Baseline and weeks 6 and 12 after treatment initiation

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

  Baseline and weeks 6 and 12 after treatment initiation

• Frailty Assessment

  Baseline and weeks 6 and 12 after treatment initiation

Study Arms (1)

Treatment (cabozantinib)

EXPERIMENTAL

Patients 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

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Given PO

Also known as: Cometriq, Cabometyx, BMS-907351, XL184, 1140909-48-3

Treatment (cabozantinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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).

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Emory University: lead
• Exelixis: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• 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.

  PMID: 39149474 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Mehmet Asim Bilen, MD
• Organization: Emory University

mehmet.a.bilen@emory.edu

404-778-1900

Study Officials

• Mehmet Asim Bilen, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 15, 2019
• First Posted: July 17, 2019
• Study Start: August 6, 2019
• Primary Completion: February 2, 2022
• Study Completion (Estimated): December 9, 2026
• Last Updated: May 5, 2026
• Results First Posted: August 13, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)