Chemotherapy + Radiation for Bladder Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must not be taking: Antiretrovirals, Antibiotics

Disqualifiers: Small cell histology, Prior chemotherapy, Others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Varies by treatment arm

78 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim of this study is to evaluate a risk-adapted approach to the treatment of muscle invasive bladder cancer. Each baseline transuretheral resection of bladder tumor (TURBT) sample will be sequenced while proceeding with neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) chemotherapy. Based on the mutational profile and the post AMVAC TURBT findings, patients will be treated with active surveillance (experimental arm), or standard of care intravesicle therapy, chemoradiation or surgery. We hypothesize that this approach will lead to non-inferior metastasis-free survival at 2 years, while preserving the bladder and thus quality-of-life for a proportion of patients.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on experimental agents or certain treatments for other cancers, you may need to stop those before joining the trial.

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

Research shows that combinations of drugs like methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) can lead to complete remission in 20 to 35% of bladder cancer cases and partial remission in an additional 20 to 40% of cases. Some patients have experienced complete remission lasting from 2 to more than 10 years. ^{1 2 3 4 5}

Is the chemotherapy and radiation treatment for bladder cancer safe?

The chemotherapy drugs used for bladder cancer, like doxorubicin and methotrexate, can have side effects such as mild to moderate bladder irritation and, in rare cases, more serious reactions like reduced bladder capacity or nausea. However, these side effects are generally manageable, and severe reactions are uncommon. ^{6 7 8 9 10}

How does the chemotherapy and radiation treatment for bladder cancer differ from other treatments?

This treatment combines chemotherapy drugs like doxorubicin and methotrexate with radiation, which is different from the standard MVAC regimen that includes cisplatin. The combination aims to enhance effectiveness, but the optimal regimen for bladder cancer is still undetermined, and more effective treatments with less toxicity are needed. ^{1 9 11 12 13}

Eligibility Criteria

This trial is for adults with muscle-invasive bladder cancer, without lymph node or distant metastases, and a good performance status. They must have urothelial carcinoma and normal heart function plus adequate organ and bone marrow function. Exclusions include prior pelvic radiation, recent experimental drugs, uncontrolled illnesses, pregnancy, other cancers within 5 years (except non-melanoma skin), previous chemo for urothelial carcinoma within a year or any chemo within a year.

Inclusion Criteria

There is evidence that the cancer has spread into the muscle layer of the organ.

My cancer is at a stage where it has grown but not spread to distant parts.

My cancer is mainly in the bladder and is of urothelial type.

Exclusion Criteria

I have no other cancers except for non-melanoma skin cancer or have been cancer-free for 5 years.

I haven't had chemotherapy or radiation for bladder cancer or any cancer treatment in the last year.

I am allergic to certain chemotherapy drugs or similar medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) chemotherapy

6-12 weeks

Post-Chemotherapy Assessment

Based on mutational profile and post-AMVAC TURBT findings, patients are assigned to different treatment arms

4 weeks

Treatment

Participants receive treatment based on risk-adapted approach: active surveillance, intravesicle therapy, chemoradiation, or surgery

Varies by treatment arm

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Doxorubicin
• Methotrexate
• Transurethral Resection of Bladder tumor
• Vinblastine

Trial Overview The RETAIN study tests whether personalized treatment based on genetic sequencing of tumor samples can maintain survival rates while preserving the bladder after neoadjuvant AMVAC chemotherapy. Patients may undergo active surveillance or standard treatments like intravesical therapy, chemoradiation or surgery depending on their response to initial treatment.

Participant Groups

Group I: Surveillance Experimental Treatment 5 Interventions

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then active surveillance

Group II: Radical Cystectomy Experimental Treatment 5 Interventions

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then cystectomy

Group III: Intravesicle therapy Experimental Treatment 5 Interventions

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then intravesicle therapy followed by TURBT#3

Group IV: CRT Experimental Treatment 8 Interventions

Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then chemoradiation followed by TURBT#3

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

Approved in United States as Adriamycin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in European Union as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Canada as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Japan as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current chemotherapy of locally advanced or metastatic bladder tumors]. Dourthe, LM., Ceccaldi, B., Fournier, R., et al.[2006]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in the management of bladder tumours. Whitmore, WF., Yagoda, A.[2018]

References

1. France pubmed.ncbi.nlm.nih.gov

[Current chemotherapy of locally advanced or metastatic bladder tumors]. [2006]

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

Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710). [2023]

3. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

A randomized trial comparing intravesical instillations of mitoxantrone and doxorubicin in patients with superficial bladder cancer. [2015]

4. Japan pubmed.ncbi.nlm.nih.gov

[Two cases of urothelial cancer responsive to high-dose-intensity methotrexate vinblastine doxorubicin and cisplatin (M-VAC) therapy]. [2013]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Chemotherapy in the management of bladder tumours. [2018]

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

Complications of intravesical chemotherapy. [2013]

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

Effect of relative cumulative dose-intensity on survival of patients with urothelial cancer treated with M-VAC. [2017]

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

Phase II trial of weekly paclitaxel, cisplatin plus infusional high dose 5-fluorouracil and leucovorin for metastatic urothelial carcinoma. [2015]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Toxicity and results of MVAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy in advanced urothelial carcinoma. [2019]

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

Phosphatidylinositol- 3-kinase inhibitor induces chemosensitivity to a novel derivative of doxorubicin, AD198 chemotherapy in human bladder cancer cells in vitro. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Adjuvant chemotherapy with doxorubicin (Adriamycin) and 5-fluorouracil in T3, NX, MO bladder cancer treated with radiotherapy. [2019]

12. Japan pubmed.ncbi.nlm.nih.gov

[Characteristic and effective usage of adriamycin]. [2013]

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

Chemotherapy in advanced urinary bladder cancer. [2019]