Bladder (Urothelial, Transitional Cell) Cancer Metastatic or UnresectablePhase 4SELECTIO-UCNCT06820255
DDR Genes Alteration and Response to Platinum-based Chemotherapy in Advanced Urothelial Cancer.
A Phase 4 study testing Platinum + Gemcitabine, Avelumab first-line maintenance and NGS test for DDR alterations in people with Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable and Upper Tract Urothelial Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
This study aims to prospectively observe whether certain alterations in some genes related to the DNA repair mechanism are related to better response to platinum-based chemotherapy used to treat metastatic bladder or urothelial cancers. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable, Upper Tract Urothelial Cancer
- What is being tested?
- Platinum + Gemcitabine, Avelumab first-line maintenance and NGS test for DDR alterations
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 1 siteItaly
- Study dates
- 7 Jan 2025to 7 Jan 2027
- Phase
- Phase 4
- 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
- Informed consent obtained before any study-specific procedures. Patients must be able to understand and be willing to sign a written informed consent.
- Male or female patient ≥18 years of age.
- Histological or cytological documentation of urothelial cancer.
- Available tumor tissue for analysis
- Measurable disease according to Response Evaluation Criteria in Solid Tumors criteria, version 1.1.
- Eastern Cooperative Oncology Group performance status of ≤2. (Patients with ECOG PS of 2 were required to also meet the additional criteria: hemoglobin ≥10 g/dL, GFR ≥50mL/min, may not have NYHA class III heart failure).
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- Life expectancy of at least 6 months.
- Eligible to standard chemotherapy with cisplatin or carboplatin + gemcitabine as per clinical practice.
- Women of childbearing potential and men must agree to use adequate contraception since signing of the informed consent form until 180 days after the last dose of chemotherapy and 30 days after the last dose of avelumab. The investigator or a designated associate is requested to advise the subject how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommend method (or combination of methods) as per standard of care.
- Adequate bone-marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days of starting to study treatment:
- a Creatinine value <2.5 mg/dl and creatinine clearance > 30 ml/min evaluated by the Cockcroft-Gault Formula.
- b Total bilirubin ≤1∙5 × the upper limit of normal (ULN); c Alanine aminotransferase and aspartate aminotransferase ≤2 × ULN (≤5 × ULN for patients with liver involvement of their cancer); d International normalized ratio (INR) and partial thromboplastin time (PTT) ≤1∙5 × ULN. Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no prior evidence of an underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care; e Platelet count ≥100 000/mm3, hemoglobin >9 g/dl, absolute neutrophil count >1,500/mm3; f Alkaline phosphatase limit ≤2∙5 × ULN (≤5 × ULN for patients with liver involvement of their cancer).
Who cannot join
- Previous treatment for metastatic or locally advanced disease.
- Previous adjuvant therapy within 1 year from the diagnosis of metastatic disease.
- Prior treatment with immunotherapy.
- Previous or concurrent cancer that is distinct in primary site or histology from urothelial cancer within 3 years before enrollment EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ], and T1 [tumor invades lamina propria]), pT2 prostate cancer with PSA<0.01.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
- Pregnancy or breast-feeding. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment.
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- Any cardiological condition among:
- Congestive heart failure of New York Heart Association class 3 or worse.
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study drug.
- Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted).
- Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg despite optimal medical management).
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), pulmonary embolism within the 4 months before start of study medication.
- Ongoing infection higher than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 grade 2.
- Known history of human immunodeficiency (HIV) virus infection or known history of chronic hepatitis B or C.
- Any autoimmune disease that contraindicates the use of maintenance immunotherapy in case of stable or responsive disease to chemotherapy.
- Seizure disorder requiring medication.
- Symptomatic metastatic brain or meningeal tumors unless the patient is >2 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also, the patient must not be undergoing acute steroid therapy or tapering (chronic steroid therapy is acceptable provided that the dose is stable for 1 month before and after screening radiographic studies).
- History of organ allograft.
- Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event of CTCAE grade 3 or higher within 4 weeks of start of study medication.
- Non-healing wound, ulcer, or bone fracture.
- Renal failure requiring hemodialysis or peritoneal dialysis.
- Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his or her compliance in the study.
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
- Participation to another clinical trial at the time of the enrollment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione Policlinico Universitario A. Gemelli IRCCS
Rome, 00168
Roberto Iacovelli, Prof, +390630156318, roberto.iacovelli@policlinicogemelli.it
Roberto Iacovelli
About this study
Official title: Prospective Evaluation of the DDR Genes Alteration to Predict Response to Platinum-based Chemotherapy in Advanced Urothelial Cancer.
This study aims to prospectively observe whether certain alterations in some genes related to the DNA repair mechanism are related to better response to platinum-based chemotherapy used to treat metastatic bladder or urothelial cancers.
- Conditions
- Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable, Upper Tract Urothelial Cancer
- Being tested
- Platinum + Gemcitabine, Avelumab first-line maintenance, NGS test for DDR alterations
- Keywords
- DNA damage response genes, cisplatin, carboplatin
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Platinum + GemcitabineDrug
Eligible patients will be treated with platinum-based chemotherapy (i.e. cisplatin + gemcitabine or carboplatin + gemcitabine).
Avelumab first-line maintenanceDrug
Patients with stable disease or tumor response after treatment with platinum-based chemotherapy will start treatment with avelumab 800 mg fat dose Q2 weeks until progression of disease or unacceptable toxicity
NGS test for DDR alterationsDiagnostic test
All patients will be tested for DDR alterations on tumor tissue.
| Study group | Role | What they receive |
|---|---|---|
| DDR alterations positive | Active comparator | This arm included all patients with DDR alteration in urothelial cancer Receives: Drug: Platinum + Gemcitabine; Drug: Avelumab first-line maintenance; Diagnostic Test: NGS test for DDR alterations |
| DDR alterations negative | Active comparator | This arm included all patients without DDR alteration in urothelial cancer Receives: Drug: Platinum + Gemcitabine; Drug: Avelumab first-line maintenance; Diagnostic Test: NGS test for DDR alterations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) by DDR group.
The difference in ORR defined as the percentage of patients who achieve PR or CR as measured by RECIST 1.1, to the platinum-based chemotherapy between patients with metastatic or locally advanced urothelial cancer with or without DDR genes alterations.
Measured: Six months
Secondary outcomes (6)
Progression Free Survival (PFS) by DDR group.
The PFS defined as the time elapsed from start of investigational treatment to the documentation of investigator-assessed disease progression, according to RECIST 1.1 [22], or death due to any cause, whichever occurs first in patients with or without DDR genes alterations.
Measured: 12 months
Overall Survival (OS) by DDR group.
The OS is defined as time elapsed from start of treatment to the date of death due to any cause in patients with or without DDR genes alterations.
Measured: 12 months
Overall Response Rate (ORR) by treatment group.
The ORR is defined as the percentage of patients who achieve PR or CR as measured by RECIST 1.1 criteria in patients with or without DDR genes alterations between those treated with carboplatin o cisplatin.
Measured: six months
Disease Control Rate (DCR) by treatment group.
The disease control rate (DCR) is defined as the percentage of patients who achieve stable disease (SD), or PR or CR as measured by RECIST 1.1 criteria in patients treated with carboplatin o cisplatin.
Measured: six months
Disease Control Rate (DCR) by DDR group.
The disease control rate (DCR) is defined as the percentage of patients who achieve stable disease (SD), or PR or CR as measured by RECIST 1.1 criteria in patients with or without DDR genes alterations.
Measured: six months
Treatment-related toxicity
The treatment-related toxicity will be evaluated by the incidence of chemo-related adverse events in patients with or without DDR genes alterations graded according to NCI CTCAE version 5.0.
Measured: 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2025
- Study start7 Jan 2025
- Primary completion7 Jan 2026 (estimated)
- Study completion7 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder (Urothelial, Transitional Cell) Cancer Metastatic or UnresectableStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be screened for DDR alteration on tumor tissue and treated with platinum-based chemotherapy followed by avelumab maintenance. Outcome to therapy will be evaluated based on presence or not of DDR alterations.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Roberto Iacovelli, Prof, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06820255
- Sponsor's protocol ID
- 7004
- Other IDs
- 2024-516450-21
- Acronym
- SELECTIO-UC
- Status last verified
- Jan 2025
- First submitted
- 6 Feb 2025
- Last updated
- 11 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of the DDR Genes Alteration to Predict Response to Platinum-based Chemotherapy in Advanced Urothelial Cancer.
- ClinicalTrials.gov ID
- NCT06820255
- Acronym / sponsor ID
- SELECTIO-UC / 7004
- Conditions
- Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable, Upper Tract Urothelial Cancer
- Keywords
- DNA damage response genes, cisplatin, carboplatin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 7 Jan 2025 (actual)
- Primary completion
- 7 Jan 2026 (estimated)
- Study completion
- 7 Jan 2027 (estimated)
- First posted
- 11 Feb 2025 (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 study aims to prospectively observe whether certain alterations in some genes related to the DNA repair mechanism are related to better response to platinum-based chemotherapy used to treat metastatic bladder or urothelial cancers.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will be screened for DDR alteration on tumor tissue and treated with platinum-based chemotherapy followed by avelumab maintenance. Outcome to therapy will be evaluated based on presence or not of DDR alterations.
| Arm | Type | Receives |
|---|---|---|
| DDR alterations positive | Active comparator | Drug: Platinum + Gemcitabine, Drug: Avelumab first-line maintenance, Diagnostic Test: NGS test for DDR alterationsThis arm included all patients with DDR alteration in urothelial cancer |
| DDR alterations negative | Active comparator | Drug: Platinum + Gemcitabine, Drug: Avelumab first-line maintenance, Diagnostic Test: NGS test for DDR alterationsThis arm included all patients without DDR alteration in urothelial cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Informed consent obtained before any study-specific procedures. Patients must be able to understand and be willing to sign a written informed consent.
- Male or female patient ≥18 years of age.
- Histological or cytological documentation of urothelial cancer.
- Available tumor tissue for analysis
- Measurable disease according to Response Evaluation Criteria in Solid Tumors criteria, version 1.1.
Key exclusion criteria (24 listed)
- Previous treatment for metastatic or locally advanced disease.
- Previous adjuvant therapy within 1 year from the diagnosis of metastatic disease.
- Prior treatment with immunotherapy.
- Previous or concurrent cancer that is distinct in primary site or histology from urothelial cancer within 3 years before enrollment EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ], and T1 [tumor invades lamina propria]), pT2 prostate cancer with PSA<0.01.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
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 |
|---|---|---|
| Platinum + GemcitabineEligible patients will be treated with platinum-based chemotherapy (i.e. cisplatin + gemcitabine or carboplatin + gemcitabine). | Drug | DDR alterations negative, DDR alterations positive |
| Avelumab first-line maintenancePatients with stable disease or tumor response after treatment with platinum-based chemotherapy will start treatment with avelumab 800 mg fat dose Q2 weeks until progression of disease or unacceptable toxicity | Drug | DDR alterations negative, DDR alterations positive |
| NGS test for DDR alterationsAll patients will be tested for DDR alterations on tumor tissue. | Diagnostic test | DDR alterations negative, DDR alterations positive |
Primary outcome
Overall Response Rate (ORR) by DDR group.
Time frame: Six months
The difference in ORR defined as the percentage of patients who achieve PR or CR as measured by RECIST 1.1, to the platinum-based chemotherapy between patients with metastatic or locally advanced urothelial cancer with or without DDR genes alterations.
6 secondary outcomes
Progression Free Survival (PFS) by DDR group.
Time frame: 12 months
Overall Survival (OS) by DDR group.
Time frame: 12 months
Overall Response Rate (ORR) by treatment group.
Time frame: six months
Disease Control Rate (DCR) by treatment group.
Time frame: six months
Disease Control Rate (DCR) by DDR group.
Time frame: six months
Treatment-related toxicity
Time frame: 12 months.
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 11 Feb 2025.
- 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.
Roberto Iacovelli, Prof principal investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Platinum + Gemcitabine, Avelumab first-line maintenance and NGS test for DDR alterations in people with Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable and Upper Tract Urothelial Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
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 12 inclusion and 24 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 11 Feb 2025. 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 Italy. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Roberto Iacovelli, Prof (+390630157373, roberto.iacovelli@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) by DDR group. (time frame: Six 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 11 Feb 2025.