Combining enfortumab vedotin with radiation for advanced bladder cancer

Enfortumab Vedotin With Radiation for Locally Advanced Bladder Cancer (CONSOLIDATE)

This study is testing whether combining a new drug called enfortumab vedotin with radiation can help people with advanced bladder cancer live longer and feel better.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 41 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (other)
• Drugs / interventions: radiation, prednisone, enfortumab
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06434350 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of enfortumab vedotin in combination with radiation therapy for patients with locally advanced muscle-invasive bladder cancer (MIBC). The study aims to estimate progression-free survival, evaluate safety and tolerability, and assess the impact on quality of life. Participants will be monitored for overall survival and metastasis-free survival, as well as treatment-related toxicities. Additionally, the trial will explore the relationship between biomarkers and patient outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with pathologically confirmed locally advanced urothelial carcinoma of the bladder.

Not a fit: Patients with non-urothelial bladder cancers or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve disease control and quality of life for patients with advanced bladder cancer.

How similar studies have performed: Other studies have shown promising results with similar combinations of targeted therapies and radiation, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Pathologically confirmed diagnosis of urothelial carcinoma of the bladder including patients with T4N0 and T1-4N2-3 disease. Participants with mixed urothelial carcinoma of bladder will also be included.
2. Be ≥ 18 years of age on the day of signing informed consent.
3. ECOG performance status 0-2. NOTE: If participants is unable to walk due to paralysis, but is mobile in a wheelchair, participants is ambulatory for the purpose of assessing their performance status.
4. The participant has the following baseline laboratory data:

   1. Hemoglobin ≥ 9 g/dL
   2. Platelet count ≥ 100 x 109 g/dL
   3. Creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards (glomerular filtration rate \[GFR\] can also be used instead of CrCl)
   4. Absolute neutrophil count (ANC) ≥ 1500/mm3
5. Male participants must consistently use highly effective methods of birth control starting at screening and continue throughout study period and for at least 6 months after radiation completion
6. Female participants must consistently use highly effective methods of birth control starting at screening and continue throughout the study period and for at least 6 months after radiation completion As the CORe system in MDACC is set up as a one-step enrollment process, the above inclusion criteria will be assessed prior to CORe enrollment. Following CORe enrollment, the below inclusion criteria will be assessed.

1\. Candidate for definitive local therapy to active disease per the discretion of the treating physicians.

Exclusion Criteria:

1. Has a diagnosis of active scleroderma, lupus, ulcerative colitis, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy.
2. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as determined by the treating physician and/or member of the study team.
3. Distant metastatic disease beyond lymph node metastases, which by the discretion of the treating physician cannot be treated definitively in a radiation field
4. Has history of prior pelvic radiation therapy
5. Has ongoing clinically significant toxicity (Grade 2 or higher with exception of alopecia) associated with prior systemic therapy
6. History of uncontrolled diabetes mellitus within 3 months of enrollment. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c between 7 and \< 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
7. Has estimated life expectancy of less than 12 weeks
8. Has preexisting sensory or motor neuropathy Grade ≥ 2
9. Participants receiving ongoing systemic intravenous antimicrobial treatment for active infection at time of randomization
10. Participants have a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. No testing for hepatitis B and hepatitis C is required unless mandated by local health authority.
11. Has a known history of human immunodeficiency virus (HIV) infection. Testing is not required unless mandated by the local health authority.
12. Has conditions requiring high doses of steroids (\>10 mg/day of prednisone or equivalent) or other immunosuppressive medications are excluded. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
13. Has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
14. Has received a prior allogeneic stem cell or solid organ transplant.
15. Has active tuberculosis As the CORe system in MDACC is set up as a one-step enrollment process, the above inclusion criteria will be assessed prior to CORe enrollment. Following CORe enrollment, the below exclusion criteria will be assessed.

1\. Is pregnant or expecting to conceive within the projected duration of the trial at the screening visit.

* Female participants of childbearing potential should have a negative urine or serum pregnancy within 6 weeks prior to study registration up to the first fraction of radiation.
* Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Where this trial is running

Houston, Texas

• MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: Comron Hassanzadeh, MD — M.D. Anderson Cancer Center
• Study coordinator: Comron Hassanzadeh, MD

Conditions: Advanced Bladder Cancer