60 Participants Needed

Chemotherapy + Durvalumab for Bladder Cancer

MC
Overseen ByMatthew Campbell
Stay on Your Current MedsYou can continue your current medications while participating
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This trial is testing if adding durvalumab to standard chemotherapy improves outcomes for bladder cancer patients whose cancer has spread to pelvic lymph nodes. Durvalumab helps the immune system attack cancer cells, potentially making the treatment more effective.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medication, you must stop it 28 days before the first dose of the study drug, unless it's a low-dose corticosteroid. It's best to discuss your specific medications with the trial team.

What evidence supports the effectiveness of the drug combination used in the Chemotherapy + Durvalumab for Bladder Cancer trial?

Research shows that combinations of cisplatin, methotrexate, vinblastine, and doxorubicin (known as MVAC) have been effective in treating bladder cancer, with some patients experiencing complete or partial remission. Although these combinations can be toxic, they have shown a response rate of up to 52% in some studies, indicating potential effectiveness in managing advanced bladder cancer.12345

Is the combination of chemotherapy drugs including cisplatin, methotrexate, vinblastine, doxorubicin, and durvalumab safe for humans?

The combination of chemotherapy drugs like cisplatin, methotrexate, vinblastine, and doxorubicin has been used in treating bladder cancer, but it can cause significant side effects, including blood-related issues like low white blood cell counts. Managing these side effects is important to avoid reducing or stopping treatment. Durvalumab, a newer drug, is generally considered safe, but its combination with these chemotherapy drugs should be monitored closely for safety.56789

What makes the drug combination of Chemotherapy + Durvalumab unique for bladder cancer?

This treatment combines chemotherapy drugs with Durvalumab, an immunotherapy drug that helps the immune system attack cancer cells, potentially offering a novel approach by enhancing the body's natural defenses alongside traditional chemotherapy.110111213

Research Team

Matthew T Campbell | MD Anderson Cancer ...

Matthew Campbell, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with bladder cancer that has spread to pelvic lymph nodes but not beyond. They must be in good physical condition, have a life expectancy of at least 12 weeks, weigh over 30 kg, and have proper heart and organ function. Women who can bear children need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

Your heart is pumping blood normally.
I agree to provide tissue samples for biopsy before starting treatment.
My doctor confirmed a lymph node in my pelvis can be biopsied.
See 8 more

Exclusion Criteria

I have not had a stroke, heart attack, or severe chest pain in the last 6 months.
I have had an organ transplant from another person.
I have another cancer that is getting worse or needs treatment.
See 18 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neo-adjuvant cisplatin chemotherapy (NAC) or NAC plus durvalumab. Durvalumab is administered one week prior to the initial cycle and then with each additional cycle of dose-dense MVAC.

12 weeks
Every 14 days for up to 6 cycles

Surgery

Patients undergo radical cystectomy or biopsy if no longer surgical candidates.

Within 90 days post-treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood and urine collected at baseline, week 2, week 6, week 16, and at the 6-week post-surgery visit.

6 weeks post-surgery

Maintenance

Durvalumab is continued as maintenance every 4 weeks until either relapse or 1 year.

Up to 1 year

Treatment Details

Interventions

  • Cisplatin
  • Doxorubicin Hydrochloride
  • Durvalumab
  • Methotrexate
  • Vinblastine
Trial OverviewThe study compares standard chemotherapy (cisplatin) with or without Durvalumab in patients with urothelial carcinoma of the bladder. Participants will be randomly assigned to receive either just chemotherapy or chemotherapy plus Durvalumab, which continues as maintenance for up to one year.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm B: Intervention with dose-dense MVAC plus DurvalumabExperimental Treatment6 Interventions
Durvalumab will be administered one week prior to the initial cycle of dose-dense MVAC and then with each additional cycle of dose-dense MVAC on Arm B
Group II: Arm A: Standard of Care with dose-dense MVACExperimental Treatment6 Interventions
The patient will receive treatment every 14 days for up to 6 cycles in the neoadjuvant setting.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

πŸ‡ͺπŸ‡Ί
Approved in European Union as Platinol for:
  • Testicular cancer
  • Ovarian cancer
  • Cervical cancer
  • Bladder cancer
  • Head and neck cancer
  • Esophageal cancer
  • Lung cancer
  • Mesothelioma
  • Brain tumors
  • Neuroblastoma
πŸ‡ΊπŸ‡Έ
Approved in United States as Platinol for:
  • Testicular cancer
  • Ovarian cancer
  • Cervical cancer
  • Bladder cancer
  • Head and neck cancer
  • Esophageal cancer
  • Lung cancer
  • Mesothelioma
  • Brain tumors
  • Neuroblastoma
πŸ‡¨πŸ‡¦
Approved in Canada as Platinol for:
  • Testicular cancer
  • Ovarian cancer
  • Cervical cancer
  • Bladder cancer
  • Head and neck cancer
  • Esophageal cancer
  • Lung cancer
  • Mesothelioma
  • Brain tumors
  • Neuroblastoma
πŸ‡―πŸ‡΅
Approved in Japan as Platinol for:
  • Testicular cancer
  • Ovarian cancer
  • Cervical cancer
  • Bladder cancer
  • Head and neck cancer
  • Esophageal cancer
  • Lung cancer
  • Mesothelioma
  • Brain tumors
  • Neuroblastoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

AstraZeneca

Industry Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from Γ‰cole nationale vΓ©tΓ©rinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from Γ‰cole nationale vΓ©tΓ©rinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Intravesical treatments with thiotepa, doxorubicin, mitomycin C, or Bacillus Calmette-Guerin have proven beneficial for managing superficial bladder tumors, although the specific indications for each treatment need further clarification.
For metastatic bladder cancer, cisplatin combined with doxorubicin or methotrexate shows significant efficacy, achieving complete remission in 20-35% of cases and partial remission in an additional 20-40%, with some patients maintaining complete remission for over 10 years.
Chemotherapy in the management of bladder tumours.Whitmore, WF., Yagoda, A.[2018]
Standard chemotherapy for transitional cell carcinoma of the bladder, known as MVAC (cisplatin, methotrexate, vinblastine, and doxorubicin), shows a high response rate but rarely leads to long-term survival, indicating a need for more effective and less toxic treatments.
Alternative agents like paclitaxel, gemcitabine, and gallium nitrate have demonstrated significant activity, either alone or in combination with cisplatin or carboplatin, achieving response rates of 40% to 70% in patients with advanced disease, although the best treatment regimen is still not established.
[Current chemotherapy of locally advanced or metastatic bladder tumors].Dourthe, LM., Ceccaldi, B., Fournier, R., et al.[2006]
Cisplatin and methotrexate are the most effective chemotherapy agents for metastatic transitional cell carcinoma, and their inclusion in polychemotherapy regimens, particularly MVAC, improves complete remission rates.
Despite the improved remission rates with polychemotherapy, only about 10-15% of patients achieve a durable response, and the treatment is associated with significant toxicity, highlighting the need for further research on optimal treatment strategies.
[Chemotherapy of bladder carcinoma. Current status and trends].Block, T.[2007]

References

Chemotherapy in the management of bladder tumours. [2018]
[Current chemotherapy of locally advanced or metastatic bladder tumors]. [2006]
[Chemotherapy of bladder carcinoma. Current status and trends]. [2007]
M-VAC or MVC for the treatment of advanced transitional cell carcinoma: metastatic, induction, and adjuvant. [2019]
Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group. [2018]
Management of cisplatin-associated toxicities in bladder cancer patients. [2021]
Combination cisplatin and dichloromethotrexate in patients with advanced bladder cancer. Phase 2. A Southwest Oncology Group study. [2019]
Neoadjuvant Dose Dense MVAC versus Gemcitabine and Cisplatin in Patients with cT3-4aN0M0 Bladder Cancer Treated with Radical Cystectomy. [2022]
Adverse events of MVAC chemotherapy in patients with advanced urothelial cancer of the bladder. [2013]
[Why use chemotherapy in cancer of the bladder? What are the initial limitations]. [2013]
11.United Statespubmed.ncbi.nlm.nih.gov
Chemotherapy of Metastatic Bladder Cancer. [2019]
Chemotherapy of advanced transitional-cell carcinoma of the bladder. [2019]
Therapy of metastatic bladder carcinoma. [2020]