Urothelial CarcinomaPhase 2CabUCNCT04066595
Cabozantinib in Patients With Locally Advanced or Metastatic Urothelial Cell Carcinoma.
A Phase 2 study testing Cabozantinib in people with Urothelial Carcinoma, run by Johannes Gutenberg University Mainz at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma
- 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
- 7 participants
- Where
- 1 siteGermany
- Study dates
- 10 Feb 2020to 1 Jul 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- 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).
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- 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.
Who cannot join
- 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;
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- 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.
- Urine protein-to-creatinine ratio (UPCR) > 1 mg/mg (> 113.2 mg/mmol)
- Symptomatic brain metastases or leptomeningeal disease (in case of clinical suspicion of central nervous system involvement confirmed by existing CT or MRI scan of the brain).
- History of another neoplasm except non-metastatic melanoma skin cancers, carcinoma in situ of the cervix, treated patients with incidental prostate cancer (pT2 (after RPE), Gleason ≤ 6) and PSA (prostate specific antigen) ≤ 0.5 ng/mL, or cancer cured by surgery, small field radiation or chemotherapy <5 years prior to enrollment.
- History of inflammatory bowel disease, significant bowel obstruction, GI disorder with a high risk of perforation or fistula.
- Any of the following events within 6 months prior to inclusion: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant arrhythmias (grade 3-4).
- Concurrent treatment with strong inhibitors of cytochrome P450 3A4 (including but not limited to cyclosporin, erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital salt with quinidine, ritonavir, valspodar, verapamil, St John's wort, rifampicin) or patients planning to receive these treatments. For patients who were receiving treatment with such agents, a one-week washout period is required prior to enrollment.
- Currently receiving any other investigational agent or received an investigational agent within 30 days (or within 5 times the half-life of this agent) before the first dose of cabozantinib.
- Significant allergy to a pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the patient.
- History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
- Active substance abuse (including active alcohol abuse).
- Medical or psychological conditions that would jeopardize an adequate and orderly completion of the trial.
- Women who are pregnant or breastfeeding.
- Women of childbearing potential (WOCBP, a woman is considered of childbearing potential i.e. fertile, following menarche and until becoming post-menopausal (defined as spontaneous amenorrhea for at least a year) or permanently sterilized (e.g. bilateral oophorectomy, hysterectomy, bilateral salpingectomy)), unless they have a negative serum or urine pregnancy test within 7 days prior to first dose of cabozantinib. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG (human chorionic gonadotropin).
- Women of childbearing potential, unless they agree to practice a highly effective and medically accepted contraception method during trial and for 4 months after last dose of study drug. A highly effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as:
- combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- oral
- intravaginal
- transdermal
- progestogen-only hormonal contraception associated with inhibition of ovulation:
- oral
- injectable
- implantable
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- vasectomized partner (medical assessment must be present and done)
- sexual abstinence when this is in line with the preferred and usual lifestyle of the subject
- Sexually active male subjects, unless they agree to use contraception (condom, contraception for non-pregnant WOCBP partner) with their partners throughout the study and for 4 months after last dose of study drug and agree to inform the Investigator if the respective partner becomes pregnant during this time.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Urology of the University Medical Center Mainz
Mainz, 55131
About this study
Official title: Cabozantinib in Patients With Locally Advanced or Metastatic Urothelial Cell Carcinoma Who Have Progressed After Cisplatin-based Chemotherapy and Anti-PD-1/PD-L1 Therapy or After Anti-PD-1/PD-L1 Therapy Only.
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
- Being tested
- Cabozantinib
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Also called Cabometyx
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cabozantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (7)
Progression-free survival (PFS)
PFS is defined as the time from first intake of trial medication to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm.
Measured: Through study completion, up to approximately 2 years
1-year survival
Rate of subjects surviving for at least one year after first intake/dose of trial medication
Measured: 1 year
Overall survival
The time between first application of trial medication to date of death due to any cause
Measured: Through study completion, up to approximately 2 years
Clinical benefit rate
Complete or partial response or stable disease for ≥ 6 months according to RECIST 1.1
Measured: Through study completion, up to approximately 2 years
Response duration
Duration of response in months from the first response (CR or PR) to progress after first intake of treatment medication
Measured: Through study completion, up to approximately 2 years
Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.
Measured: Through study completion, up to approximately 2 years
Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs)
The number of participants who discontinue study treatment due to an AE will be presented.
Measured: Through study completion, up to approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2019
- Study start10 Feb 2020
- Primary completion1 Jul 2021
- Study completion1 Jul 2021
Why it stopped: Recruitment problems
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CarcinomaStudies 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
- Single group
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johannes Gutenberg University Mainz
- Sponsor type
- University, hospital or other
- Collaborators
- Interdisciplinary Center Clinical Trials (IZKS), University Medical Center Mainz
- Responsible party
- Principal investigator, Georg Bartsch, Johannes Gutenberg University Mainz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04066595
- Sponsor's protocol ID
- CabUC
- Acronym
- CabUC
- Status last verified
- Aug 2021
- First submitted
- 21 Aug 2019
- Last updated
- 30 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cabozantinib in Patients With Locally Advanced or Metastatic Urothelial Cell Carcinoma Who Have Progressed After Cisplatin-based Chemotherapy and Anti-PD-1/PD-L1 Therapy or After Anti-PD-1/PD-L1 Therapy Only.
- ClinicalTrials.gov ID
- NCT04066595
- Acronym / sponsor ID
- CabUC / CabUC
- Conditions
- Urothelial Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment problems
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Johannes Gutenberg University MainzUniversity, hospital or other
- Collaborators
- Interdisciplinary Center Clinical Trials (IZKS), University Medical Center Mainz
- Study start
- 10 Feb 2020 (actual)
- Primary completion
- 1 Jul 2021 (actual)
- Study completion
- 1 Jul 2021 (actual)
- First posted
- 26 Aug 2019 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Experimental (cohorts 1 and 2) | Experimental | Drug: CabozantinibCohort 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (43 listed)
- 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:
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: Cabometyx60 mg cabozantinib oral daily. When dose reduction is necessary, it is recommended to reduce to 40 mg daily, and then to 20 mg daily. | Drug | Experimental (cohorts 1 and 2) |
Primary outcome
Objective response rate after 6 months of cabozantinib treatment
Time frame: 6 months
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.
7 secondary outcomes
Progression-free survival (PFS)
Time frame: Through study completion, up to approximately 2 years
1-year survival
Time frame: 1 year
Overall survival
Time frame: Through study completion, up to approximately 2 years
Clinical benefit rate
Time frame: Through study completion, up to approximately 2 years
Response duration
Time frame: Through study completion, up to approximately 2 years
Number of Participants with Adverse Events (AEs)
Time frame: Through study completion, up to approximately 2 years
Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs)
Time frame: Through study completion, up to approximately 2 years
Results and safety
The study was stopped early (reason given: Recruitment problems). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2021.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 in people with Urothelial Carcinoma, run by Johannes Gutenberg University Mainz at 1 site in Germany.
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 43 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: stopped early, as of the sponsor's last update on 30 Aug 2021. 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 Germany. 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?
The study was stopped early (reason given: Recruitment problems). Results are not available in the source record.
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 after 6 months of cabozantinib treatment (time frame: 6 months). 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 30 Aug 2021.