Cabozantinib in Patients With Locally Advanced or Metastatic Urothelial Cell Carcinoma.

NCT04066595 | Terminated Phase 2 DMC

• 1 other identifier: CabUC
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

In this Phase II study we investigate the benefit of cabozantinib treatment for patients with locally advanced or metastasized urothelial cell carcinoma who have been pre-treated with checkpoint inhibitors only (cohort 1) or who have been pre-treated with cisplatin-based chemotherapy and checkpoint inhibitors (cohort 2). We are lacking adequate response and outcome data in patients after immunotherapy and consider that this study will improve future treatment modalities for this important patient cohort.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate after 6 months of cabozantinib treatment

  The response rate is defined as the percentage of subjects with a confirmed reduction in tumor size compared to baseline as well as fulfilling the criteria for complete or partial response according to RECIST 1.1. The response to treatment is measured by computer tomography (CT) every 12 weeks starting from the first day of cabozantinib treatment.

  6 months

Secondary Outcomes (7)

• Progression-free survival (PFS)

  Through study completion, up to approximately 2 years

• 1-year survival

  1 year

• Overall survival

  Through study completion, up to approximately 2 years

• Clinical benefit rate

  Through study completion, up to approximately 2 years

• Response duration

  Through study completion, up to approximately 2 years

Study Arms (1)

Experimental (cohorts 1 and 2)

EXPERIMENTAL

Cohort 1 will consist of patients who have been pre-treated with checkpoint inhibitors only (2nd line setting for cabozantinib). Cohort 2 will consist of patients who have been pre-treated with cisplatin-based chemotherapy and checkpoint inhibitors (3rd line setting for cabozantinib). Both cohorts receive the same treatment.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

60 mg cabozantinib oral daily. When dose reduction is necessary, it is recommended to reduce to 40 mg daily, and then to 20 mg daily.

Also known as: Cabometyx

Experimental (cohorts 1 and 2)

Eligibility Criteria

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

You may qualify if:

• Ability of subject to understand nature, importance and individual consequences of clinical trial.
• Signed and dated informed consent of the subject must be available before start of any specific trial procedures.
• Male or female patients ≥ 18 years
• Life expectancy ≥ 10 weeks, by judgment of the Investigator.
• Patients must be able to swallow intact tablets.
• Patients with histology/cytology confirmed urothelial carcinoma (UC) including mixed pathology with predominantly UC, with locally advanced (T4b) or metastatic (lymph node or visceral) UC arising from bladder or upper urinary tracts. Patients with measurable disease (at least one tumor lesion measurable on radiographic imaging as defined by RECIST 1.1).
• ECOG (Eastern Cooperative Oncology Group) Performance Status 0-1.
• Cohort 1: patients who have been pre-treated with checkpoint inhibitors only for one of the following reasons: glomerular filtration rate more ≥30 ml/min and ≤ 60 ml/min (Cockcroft-Gault formula), grade 2 or higher hearing loss or peripheral neuropathy. Cohort 2: patients who have been pre-treated with cisplatin-based chemotherapy and checkpoint inhibitors.
• Recurrence within 12 months (by RECIST criteria version 1.1) from last cycle of chemotherapy or PD-1/PD-L1 therapy.
• Recovery to baseline or ≤ Grade 1 CTCAE v.5.0 from toxicities related to any prior treatments, unless the side effects are clinically non-significant and/or stable on supportive therapy.

You may not qualify if:

• Radiation, chemotherapy, or other anti-cancer therapy \< 4 weeks prior to enrollment in the study.
• Patients previously treated with small molecule tyrosine kinase inhibitors.
• Systemic treatment with radionuclides \< 4 weeks prior to enrollment in the study, and subjects with clinically relevant ongoing complications from prior radiation therapy.
• Abdominal surgery \<10 weeks prior to enrollment in the study. Complete wound healing must be observed at least 10 days prior to enrollment, and patients should not have relevant ongoing complications at study enrollment.
• Inadequate organ and bone marrow function as evidenced by:
• Hemoglobin \<9.0 g/dL;
• HbA1c \> 8%;
• Absolute neutrophil count \<1.5 x 109/L;
• Platelet count \<100 x 109/L;
• Fasting serum triglycerides \> 2.5 x ULN and total cholesterol \> 300 mg/dL. Lipid-lowering medication is allowed;
• AST (aspartate aminotransferase) /SGOT (serum glutamate oxaloacetate transaminase) and/or ALT (alanine aminotransferase)/SGPT (serum glutamate pyruvate transaminase) ≥3.0 x ULN (upper limit of normal);
• Total bilirubin \>1.5 x ULN (upper limit of normal), for subjects with Gilbert's disease \> 3 mg/dL;
• Serum creatinine \>2.0 x ULN;
• Creatinine clearance ≤ 30 mL/min (Cockroft-Gault formula);
• PT (prothrombin time) or INR (international normalized ratio) or PTT (partial thromboplastin time) ≥ 1.3 x ULN.

Sponsors & Collaborators

• Johannes Gutenberg University Mainz: lead
• Interdisciplinary Center Clinical Trials (IZKS), University Medical Center Mainz: collaborator

Study Sites (1)

Department of Urology of the University Medical Center Mainz

Mainz, 55131, Germany

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

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: Assistant Medical Director of Department of Urology and Pediatric Urology

Model Details: 2 cohorts. Cohort 1 will consist of patients who have been pre-treated with checkpoint inhibitors only (2nd line setting for cabozantinib). Cohort 2 will consist of patients who have been pre-treated with cisplatin-based chemotherapy and checkpoint inhibitors (3rd line setting for cabozantinib).

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: August 26, 2019
• Study Start: February 10, 2020
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: August 30, 2021

Record last verified: 2021-08

Locations

DE (1)