Enfortumab Vedotin + Radiation for Bladder Cancer

Overseen By Comron Hassanzadeh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Scleroderma, Lupus, Ulcerative colitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 4-5 weeks

41 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on high doses of steroids or other immunosuppressive medications, you may not be eligible to participate.

What data supports the effectiveness of the treatment Enfortumab Vedotin + Radiation for Bladder Cancer?

Research shows that advances in radiation therapy, like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), improve treatment accuracy and effectiveness for bladder cancer. Additionally, combining radiation with chemotherapy has been shown to enhance results, suggesting that combining Enfortumab Vedotin with radiation could be promising. ^{1 2 3 4 5}

Is Enfortumab Vedotin safe for humans?

Enfortumab Vedotin has been approved for treating advanced bladder cancer, but it can cause serious side effects like high blood sugar, nerve damage, eye problems, skin reactions, and risks to unborn babies. In studies, severe side effects occurred in 73% of patients, and skin reactions were common. ^{6 7 8 9 10}

What makes the drug Enfortumab Vedotin unique for bladder cancer treatment?

Enfortumab Vedotin is unique because it is the first drug approved to treat advanced bladder cancer in patients who have already received other treatments like PD-1/PD-L1 inhibitors and platinum-based chemotherapy. It works by targeting a protein called Nectin-4 on cancer cells, delivering a toxic substance directly to them, which is different from traditional chemotherapy that affects both cancerous and healthy cells. ^{6 7 8 9 11}

What is the purpose of this trial?

To learn if the combination of enfortumab vedotin plus radiation therapy could help to control the disease.

Research Team

Comron Hassanzadeh, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 with advanced bladder cancer who are candidates for local therapy. They must use effective birth control and have adequate blood counts, kidney function, and an ECOG performance status of 0-2. Exclusions include significant prior treatment toxicity, HIV, certain immune conditions, uncontrolled diabetes or psychiatric disorders, distant metastases outside treatable areas by radiation, pregnancy or potential to conceive during the trial.

Inclusion Criteria

My doctor agrees I can have treatment aimed at curing my cancer.

I use reliable birth control methods.

I am using a reliable form of birth control.

Exclusion Criteria

I am experiencing side effects from previous cancer treatments.

I have been diagnosed with HIV.

I am not on high doses of steroids or immunosuppressants.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enfortumab vedotin by vein on Days 1 and 8 of every 28-day cycle and radiation therapy 5 times a week for about 4-5 weeks

4-5 weeks

5 visits per week (in-person) for radiation, 2 visits per cycle (in-person) for enfortumab vedotin

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Enfortumab Vedotin
• Radiation Therapy

Trial Overview The study tests if enfortumab vedotin combined with radiation can control locally advanced bladder cancer better than current treatments. Participants will receive both the drug and radiation therapy to see how well they work together against the disease.

Participant Groups

Group I: Enfortumab Vedotin with Radiation Experimental Treatment 2 Interventions

Particpants will receive enfortumab vedotin by vein over about 1-2 hours on Days 1 and 8 of every 28-day cycle. Two dose levels of enfortumab vedotin will be tested. The dose of enfortumab vedotin participants receive will depend on when the participant join the study. Participants will also receive radiation therapy 5 times a week (Monday through Friday) for about 4-5 weeks.

Enfortumab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Padcev for:

• Locally advanced or metastatic urothelial cancer

Approved in European Union as Padcev for:

• Locally advanced or metastatic urothelial cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a study of 38 patients with invasive bladder cancer, concurrent radiotherapy and panitumumab after chemotherapy resulted in a low rate of severe toxicity (16%), comparable to historical rates for cisplatin and radiotherapy.

The treatment achieved a high complete remission rate of 94%, with promising bladder preservation outcomes, suggesting that this approach could be a viable alternative for bladder cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Radiotherapy and Panitumumab after Lymph Node Dissection and Induction Chemotherapy for Invasive Bladder Cancer. Fransen van de Putte, EE., Pos, F., Doodeman, B., et al.[2019]

In a study of 487 bladder cancer patients treated with radical radiotherapy, the incidence of severe acute toxicity was relatively low, with 5% experiencing grade 3 or higher bladder toxicity and 3% for bowel toxicity, indicating that the treatment is generally safe.

The severity of acute toxicity was influenced by factors such as the T-stage of the cancer and the intensity of the radiation dose, with higher dose intensity leading to quicker onset of acute toxicity and a greater risk of late effects in both bladder and bowel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and late toxicity in radical radiotherapy for bladder cancer. Majewski, W., Tarnawski, R.[2009]

Recent advancements in radiation treatment planning and delivery for bladder cancer can improve treatment outcomes by minimizing damage to healthy tissue while allowing for higher radiation doses or more aggressive treatment schedules.

The review highlights the importance of patient selection and the use of techniques like image-guided radiotherapy and intensity-modulated radiotherapy to enhance treatment accuracy and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy for muscle-invasive bladder cancer: treatment planning and delivery in the 21st century. McBain, CA., Logue, JP.[2019]

Radiotherapy remains the most effective non-surgical treatment for bladder cancer, with advancements in three-dimensional imaging improving accuracy and reliability in treatment planning.

Combining radiotherapy with chemoradiation has shown improved outcomes in one randomized-controlled trial, and hypoxia modification techniques are currently being evaluated for their potential benefits in enhancing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapies in bladder cancer. Alonzi, R., Hoskin, P.[2019]

In a study of 149 patients with bladder cancer, delivering a higher radiation dose to just the tumor area (partial bladder radiotherapy) did not improve local tumor control compared to whole bladder radiotherapy, with similar overall survival rates across all treatment groups.

The study found that while the increased radiation dose did not lead to higher toxicity, it also did not significantly enhance overall survival, indicating that simply increasing the dose to the tumor may not be sufficient for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy for muscle-invasive carcinoma of the bladder: results of a randomized trial comparing conventional whole bladder with dose-escalated partial bladder radiotherapy. Cowan, RA., McBain, CA., Ryder, WD., et al.[2006]

Enfortumab vedotin (PADCEV) received accelerated FDA approval for treating locally advanced or metastatic urothelial cancer in patients who have already undergone specific prior therapies, based on substantial evidence from a study involving 125 patients.

The treatment showed a confirmed objective response rate of 44%, with a median response duration of 7.6 months, although 73% of patients experienced grade 3-4 adverse reactions, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. Chang, E., Weinstock, C., Zhang, L., et al.[2022]

Enfortumab vedotin (Padcev) is the first FDA-approved treatment specifically for adults with locally advanced or metastatic urothelial cancer who have already undergone treatment with PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

This approval marks a significant advancement in cancer therapy, providing a new option for patients who have limited treatment choices after previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. Kahl, KL.[2023]

Enfortumab vedotin-ejfv (EV) is an effective treatment for locally advanced or metastatic urothelial carcinoma (UC), showing a 44% overall response rate and a median overall survival of 11.7 months in heavily pretreated patients.

While EV demonstrates significant antitumor activity, it also presents unique toxicity concerns that require careful monitoring, highlighting the need for further studies to optimize its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. Halford, Z., Anderson, MK., Clark, MD.[2021]

Enfortumab vedotin, a treatment for advanced bladder cancer, can cause severe skin reactions, with a case report highlighting a patient who developed toxic epidermal necrolysis shortly after starting the drug.

The case emphasizes the need for careful monitoring of skin reactions and suggests that if such reactions occur, treatment may need to be reduced or stopped to prevent serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma. Mimura, Y., Kobayashi, A., Utazu, H., et al.[2023]

In a study of 34 patients with metastatic urothelial carcinoma treated with enfortumab vedotin, 56% showed a partial response or stable disease, with a median overall survival of 16 months and progression-free survival of 9 months, indicating its efficacy in a real-world setting.

The treatment was associated with a high incidence of adverse events, with 76% of patients experiencing some level of toxicity, primarily skin-related, but the safety profile was consistent with findings from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort. Miyake, M., Nishimura, N., Oda, Y., et al.[2023]

Enfortumab vedotin showed a 44% overall response rate in a phase II trial involving 125 patients with locally advanced or metastatic urothelial carcinoma who had previously undergone platinum-based chemotherapy and PD-1 or PD-L1 checkpoint inhibitor treatment.

While nearly all patients experienced treatment-related adverse events, most of these side effects were mild to moderate, indicating a manageable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin Checks Urothelial Cancer. [2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Concurrent Radiotherapy and Panitumumab after Lymph Node Dissection and Induction Chemotherapy for Invasive Bladder Cancer. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Acute and late toxicity in radical radiotherapy for bladder cancer. [2009]

3. United States pubmed.ncbi.nlm.nih.gov

Radiation therapy for muscle-invasive bladder cancer: treatment planning and delivery in the 21st century. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Novel therapies in bladder cancer. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Radiotherapy for muscle-invasive carcinoma of the bladder: results of a randomized trial comparing conventional whole bladder with dose-escalated partial bladder radiotherapy. [2006]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. [2021]

9. Australia pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin Checks Urothelial Cancer. [2020]