Phase II Study of 2L Gem/Carbo After Progression on EVP in Advanced/Metastatic Urothelial Carcinoma

Not Applicable

Not yet recruiting

• Conditions: Urothelial Carcinoma
• Interventions: Drug: Gemcitabine; Drug: Carboplatin

• Registration Number: NCT07043972
• Lead Sponsor: Fox Chase Cancer Center

Brief Summary

The goal of this clinical trial is to learn if a chemotherapy combination called gemcitabine and carboplatin (GC) works to treat advanced urothelial cancer in people who have already been treated with enfortumab vedotin and pembrolizumab (EVP).

It will also learn about the efficacy and safety of GC in these patients.

The main questions it aims to answer are:

* Does GC shrink the cancer or stop it from growing?

* What medical side effects do participants have while receiving GC?

Researchers will study how GC affects survival, cancer control, and quality of life. They will also collect blood samples to look at health-related markers and cancer DNA in the blood.

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Participants will:

* Receive the GC chemotherapy (gemcitabine and cisplatin) after having been treated with EVP

* Visit the clinic regularly for checkups, lab tests, and scans

* Answer questions about their health, quality of life, and daily function

* Provide blood samples for research

This study may help researchers find better ways to treat advanced bladder and urinary tract cancer in the future-especially for older adults or those who have already tried other treatments.

Detailed Description

Primary endpoint:

• Best overall response (CR, PR, SD, PD) to GC defined per RECIST v 1.1

Secondary endpoints:

* Progression-free survival (PFS) defined as the time from treatment initiation until documented disease progression, clinical progression, death, or the end of follow-up, whichever occurs first. Those who are still alive without evidence of progression at the end of follow-up will be considered censored.

* Overall survival (OS) defined as the time from treatment initiation until death. Patients who are still alive at the end of follow-up will be considered censored.

* The number and rate of grade 1-5 toxicity defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 criteria (CTCAE 5.0) in all patients who received at least one dose of treatment on trial

* Disease control rate (DCR) defined as the proportion of patients achieving a CR, PR, or SD

Exploratory endpoints:

* We will use the EORTC QLQ-C30 as a surrogate of quality of life and measure the association of QOL with treatment tolerability and clinical outcomes. Treatment tolerability will be measured using the proportion of patients experiencing a dose modification, the proportion of patients experiencing early treatment discontinuation, the proportion of patients experiencing a grade 3 or higher treated-related adverse events (TRAEs), the number of cycles delivered, and early discontinuation of GC. Clinical outcomes will include (Overall response rate) ORR, PFS, and OS.

* We will measure biomarkers of aging (IL-6, C-reactive protein, D-Dimer, and FC-MAP) from peripheral blood samples at baseline, cycle 4, and end of treatment in older patients (over age 65 years) and measure the association between these markers with treatment tolerability (occurrence of hematologic and non-hematologic toxicity, occurrence of a dose reduction) and clinical outcomes (OR)

* We will use the battery of geriatric assessment tools selected and validated by the Cancer and Leukemia Group B (CALGB) group among older oncology patients (over age 65 years) specifically in a clinical trial setting, modified as per our institutional standard. We will measure the association between geriatric assessment values and treatment tolerability and clinical outcomes (PFS, OS)

* We will measure circulating tumor DNA (ctDNA) at baseline to evaluate molecular patterns of resistance to EVP and at specific treatment timepoints to correlate with treatment response

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-26
• Study First Submitted QC: 2025-06-26
• Last Update Submitted: 2025-06-26
• Study First Posted: 2025-06-29
• Last Update Posted: 2025-06-29
• Study Start: 2025-07-01
• Primary Completion: 2030-01-01
• Study Completion: 2031-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

• Patients must have metastatic or locally advanced histologically and radiographically confirmed urothelial carcinoma

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1

• Patients must have received treatment with enfortumab vedotin plus pembrolizumab in the first line setting. Study treatment may be started within 28 days of last treatment with EV-P or with continuing toxicities if considered by the Sponsor-Investigator to be safe and within the best interest of the patient.

• Age > 18 years.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Patients must have normal organ and marrow function as defined below.

  • Absolute neutrophil count > 1,000/mm3 unless patient has constitutional neutropenia
  • Platelets > 80,000/ul
  • Hemoglobin > 8.0 g/dL
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x ULN or <3.5 x upper limit of normal (ULN) if liver metastases
  • Creatinine Clearance >20 mL/min

• Ability to understand and willingness to sign a written informed consent and HIPAA consent document

• Optional: Archival tumor biospecimen, when available, must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin fixed paraffin embedded (FFPE) tissue block(s) or at least 15 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable.

Exclusion Criteria

• Patients who have had systemic treatment including EV-P or radiotherapy within 2 weeks prior to entering the study

• Patients who have had systemic treatment including EV-P or radiotherapy within 2 weeks prior to entering the study

• Patients who have received more than one line of prior therapy or prior platinum-based chemotherapy for locally advanced or metastatic urothelial carcinoma (neoadjuvant platinum-based therapy including cisplatin is allowed)

• Patients who have not recovered from adverse events to less than Grade 2 secondary to agents administered more than 2 weeks prior to treatment initiation.

• Patients may not be receiving any other investigational agents

• Patients with uncontrolled and untreated CNS metastases:

  • Prior radiation to central nervous system (CNS) metastases is permitted
  • Prior history of CNS disease that has responded to previous systemic therapy is permitted only if no recurrence
  • Patient should not have leptomeningeal disease
  • CNS metastases have been clinically stable for at least 6 weeks prior to screening and baseline scans show no evidence of new or enlarged metastases

• Uncontrolled intercurrent illness including, but not limited to ongoing or active untreated infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit adherence with study requirements

• Subjects with a history of another invasive malignancy within 3 years before the first dose of study drug that cannot be watched and requires tumor- directed treatment, or any evidence of residual disease from a previously diagnosed malignancy that cannot be watched and requires treatment (adjuvant hormonal therapy for breast cancer is allowed)

• Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of first dose of chemotherapy (routine antimicrobial prophylaxis is permitted)

• Pregnant or breast feeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gemcitabine plus carboplatin	Gemcitabine	Patients will be treated with gemcitabine 1,000 mg/m2 administered over 30 minutes IV on days 1 and 8, followed by carboplatin area under the curve (AUC) 5 on day 1, every 3 weeks.
Gemcitabine plus carboplatin	Carboplatin	Patients will be treated with gemcitabine 1,000 mg/m2 administered over 30 minutes IV on days 1 and 8, followed by carboplatin area under the curve (AUC) 5 on day 1, every 3 weeks.

Primary Outcome Measures

Name	Time	Method
Best overall response (Complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) to gemcitabine plus carboplatin defined per RECIST v 1.1	3 years	From the start of the treatment until disease progression/recurrence

Secondary Outcome Measures

Name	Time	Method
To evaluate progression free survival (PFS) as a function of time since study enrollment in patients receiving GC after prior exposure to EVP	3 years	From initiation of study treatment until progression or death with patients who are still alive and progression free at the end of the follow-up period considered censored at their last contact.
To evaluate overall survival (OS) as a function of time since study enrollment in patients receiving GC after prior exposure to EVP	3 years	From initiation of study treatment until death with patients still alive at the end of follow-up censored at their last contact date
To evaluate the frequency and severity of toxicities attributed to GC after prior exposure to EVP	3 years	From the start of study treatment until the patient either begins survival follow-up, starts a new cancer therapy, or die, whichever occurs first
To evaluate the disease control rate (DCR) of gemcitabine plus carboplatin after prior exposure to EVP	3 years	From initiation of study treatment until progression or death with patients who are still alive and progression free at the end of the follow-up period considered censored at their last contact

Trial Locations

Locations (2)

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Temple University Hospital at Broad Street; 🇺🇸 Philadelphia, Pennsylvania, United States