Chemotherapy + Radiation for Bladder Cancer

Not currently recruiting at 4 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating muscle-invasive bladder cancer. It combines chemotherapy (including drugs like Doxorubicin, Methotrexate, and Vinblastine) and radiation tailored to the tumor's genetic profile, with options like surgery or active monitoring based on the results. The goal is to determine if this method can effectively control the cancer while preserving the bladder and improving quality of life. People with muscle-invasive bladder cancer, who haven't received certain previous treatments, might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the chemotherapy treatment AMVAC, which includes methotrexate, vinblastine, doxorubicin, and cisplatin, has been tested for safety in treating bladder cancer. In earlier studies, patients received AMVAC before surgery to remove bladder tumors. These studies found that patients generally tolerated the treatment well. Specifically, one study indicated that AMVAC helped improve survival rates for those who could receive this chemotherapy.

While side effects can occur, they are usually manageable. Common side effects reported in studies include nausea, tiredness, and hair loss, typical with many chemotherapy drugs. It's important to discuss any concerns with healthcare providers and learn about ways to manage side effects. Overall, existing research shows that AMVAC can be a safe option for treating bladder cancer when managed properly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for bladder cancer because they combine chemotherapy, radiation, and surgical techniques in innovative ways. Unlike traditional treatments that might focus on one method, these investigational therapies leverage a trimodality approach, which includes maximal transurethral resection of bladder tumor (TURBT) followed by various combinations of chemotherapy agents like doxorubicin, methotrexate, and vinblastine. One unique feature is the use of intravesicle therapy, which delivers medication directly into the bladder, potentially reducing side effects and enhancing effectiveness. Another approach includes active surveillance, which allows for close monitoring with the possibility of avoiding overtreatment. Additionally, the option of radical cystectomy offers a surgical route for those who may benefit from bladder removal. This multi-faceted approach aims to improve outcomes by tailoring treatment to individual needs, making it a significant advancement over standard care options.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that AMVAC chemotherapy, which includes methotrexate, vinblastine, doxorubicin, and cisplatin, effectively treats muscle-invasive bladder cancer. In this trial, participants may receive AMVAC as part of different treatment arms. Studies have found that this treatment can extend patients' lives and reduce the risk of cancer recurrence. AMVAC is particularly noted for shrinking tumors before surgery, facilitating their removal. It is considered safe and effective, with manageable side effects for most patients. This treatment approach aims to preserve the bladder and enhance quality of life, offering significant benefits for many dealing with bladder cancer. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11763370/

Neoadjuvant Accelerated Methotrexate, Vinblastine, ...

The present study evaluated the effectiveness and safety of accelerated MVAC (aMVAC) chemotherapy used before the resection of the bladder due to muscle- ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39748656/

impact on surgical complications and oncological efficacy

We aimed to evaluate the utilization of NAC, perioperative complications and oncological efficacy in a real-world setting.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00005047

4B951, Combination Chemotherapy in Treating Patients ...

Compare the recurrence-free and overall survival in patients with transitional cell carcinoma of the bladder with p53 gene alterations treated with methotrexate ...

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.22.00669

Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and ...

This study aimed to explore the optimal perioperative chemotherapy regimen for patients with nonmetastatic muscle-invasive bladder cancer (MIBC) ...

5.

mdpi.com

mdpi.com/2072-6694/13/11/2770

Comparison of Oncologic Outcomes of Dose-Dense ...

Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer ...

6.

asco.org

asco.org/abstracts-presentations/ABSTRACT287091

Safety and efficacy of neoadjuvant chemotherapy (NAC) ...

Background: NAC improves survival in pts with MIBC eligible to receive cisplatin-based chemotherapy. Prospective data supports the use of aMVAC, ...

7.

thelancet.com

thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00587-9/abstract

Perioperative dose-dense methotrexate, vinblastine, ...

We found no evidence of improved overall survival with dd-MVAC over GC in the perioperative setting, but the data support the use of six cycles ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0302283825003914

Neoadjuvant Pembrolizumab and Accelerated ...

Muscle-invasive bladder cancer (MIBC) with histologic subtypes represents a clinical challenge because of poor responses to conventional ...