Immunotherapy + Chemotherapy for Bladder Cancer

(ADAPT-BLADDER Trial)

Recruiting in Palo Alto (17 mi)

+7 other locations

Overseen by Noah M. Hahn, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Noah Hahn, M.D.

Must be taking: BCG therapy

Must not be taking: Immunosuppressants, PD-1, PD-L1, CTLA-4

Disqualifiers: Muscle-invasive cancer, Active second malignancy, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Upon successful screening and registration, enrollment to durvalumab monotherapy (cohort 1) will begin. If DLT criteria outlined in the protocol are exceeded with durvalumab monotherapy (cohort 1), the study will close. Provided the safety of durvalumab monotherapy is established, enrollment to combination regimen cohorts will proceed. Cohorts will simultaneously enroll in parallel to each other with patients assigned to cohorts based on patient slot availability and study site choice of radiation arm participation. Patient assignment to future phase 1 arms would proceed similarly. Within BCG-containing cohorts, treatment will begin at full-dose BCG. If DLT criteria outlined in Section 5.1.4 are exceeded with full-dose BCG, a one level dose reduction of BCG will be implemented. If DLT criteria outlined in Section 5.1.4 are exceeded with reduced-dose BCG, the BCG-containing cohort will not proceed to Phase 2 of the study. Similarly, if DLT criteria outlined in Section 5.1.4 are exceeded within non-BCG containing cohorts, the non-BCG containing cohort will not proceed to phase 2 of the study. Due to the prolonged half-life of antibody therapies, no dose adjustments are planned for durvalumab in any of the cohorts.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medication within 14 days before starting the study drug, except for certain exceptions like low-dose steroids or NSAIDs. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of this treatment for bladder cancer?

Research shows that using gemcitabine and docetaxel together can help patients with bladder cancer who did not respond to BCG treatment, providing a durable remission. Additionally, BCG is a standard treatment for bladder cancer, and efforts to enhance its effectiveness with other therapies like immunotherapy are ongoing.

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Is the combination of immunotherapy and chemotherapy for bladder cancer safe?

Studies have shown that while Bacillus Calmette-Guérin (BCG) is effective for bladder cancer, it can have significant side effects. Alternatives like gemcitabine and docetaxel have been evaluated for safety and are considered tolerable, offering a potential option for those who cannot tolerate BCG.

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How is the Immunotherapy + Chemotherapy treatment for bladder cancer different from other treatments?

This treatment combines immunotherapy and chemotherapy, using a mix of drugs like Bacillus Calmette-Guérin (BCG), Docetaxel, Durvalumab, Gemcitabine, and Tremelimumab, which is unique because it targets the cancer in multiple ways, potentially offering a more comprehensive approach compared to traditional single-drug therapies.

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Eligibility Criteria

Adults with non-muscle invasive bladder cancer confirmed within the last 60 days, who are generally healthy and have good organ function. They must not have other active cancers (except certain skin or prostate cancers), severe medical conditions, or be pregnant/breastfeeding. Participants need to use contraception and agree to follow study rules.

Inclusion Criteria

Subjects who give a written informed consent obtained according to local guidelines

My bladder cancer is confirmed and not muscle-invasive.

I am 18 years old or older.

Exclusion Criteria

I have another cancer besides non-melanoma skin cancer or prostate cancer that is not actively growing.

I haven't had cancer treatment in the last 4 weeks or still have side effects.

My bladder cancer cannot be removed by surgery and has spread.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab monotherapy or combination regimens, including BCG, radiation, or chemotherapy, depending on cohort assignment

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for recurrence-free survival and adverse events

12 months

Extension

Optional continuation of treatment for further monitoring and assessment of long-term outcomes

12 months

Participant Groups

The trial is testing Durvalumab alone or in combination with treatments like EBRT, Gemcitabine, Docetaxel, Tremelimumab, and BCG for bladder cancer. It starts with Durvalumab; if safe, it adds other treatments. Patients join different groups based on availability and choice of radiation participation.

Group I: Phase 2: Cohort 4 Expansion Experimental Treatment 3 Interventions

Durvalumab + Gemcitabine/Intravesical Docetaxel (Gem/Doc) The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments.

Group II: Phase 1: Cohort 6 Experimental Treatment 1 Intervention

Additional Regimens (to be determined)

Group III: Phase 1: Cohort 5 Experimental Treatment 4 Interventions

NOTE: Cohort 5 was abandoned prior to any patients enrolled. Durvalumab + Tremelimumab + Gem/Doc The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments. For the intravenous medications, durvalumab should be administered first followed by tremelimumab.

Group IV: Phase 1: Cohort 4 Experimental Treatment 3 Interventions

Durvalumab + Gemcitabine/Intravesical Docetaxel (Gem/Doc) The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments.

Group V: Phase 1: Cohort 3 Experimental Treatment 2 Interventions

Durvalumab plus External Beam Radiotherapy (EBRT) (BCG re-treatment) - Cross-over to Durvalumab Monotherapy

Group VI: Phase 1: Cohort 2 Experimental Treatment 2 Interventions

Durvalumab plus BCG

Group VII: Phase 1: Cohort 1 Experimental Treatment 1 Intervention

Durvalumab monotherapy

Bacillus Calmette-Guérin (BCG) is already approved in United States, Canada, European Union for the following indications:

🇺🇸 Approved in United States as TheraCys for:

• Non-muscle invasive bladder cancer
• Upper tract urothelial carcinoma

🇨🇦 Approved in Canada as Immun BCG for:

• Non-muscle invasive bladder cancer

🇪🇺 Approved in European Union as TICE BCG for:

• Non-muscle invasive bladder cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of North Carolina at Chapel Hill Chapel Hill, NC

Washington University School of Medicine Saint Louis, MO

University of Nebraska Medical Center Omaha, NE

Columbia University Irving Medical Center New York, NY

More Trial Locations

Who Is Running the Clinical Trial?

Noah Hahn, M.D. Lead Sponsor

Hoosier Cancer Research Network Collaborator

AstraZeneca Industry Sponsor

References

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

Sequential intravesical gemcitabine/docetaxel provides a durable remission in recurrent high-risk NMIBC following BCG therapy. [2023] Bacillus Calmette-Guerin (BCG) is the standard of care for high-risk nonmuscle invasive bladder cancer (NMIBC), but half of patients develop disease recurrence. Intravesical regimens for BCG unresponsive NMIBC are limited. We report the safety, efficacy, and differential response of sequential gemcitabine/docetaxel (gem/doce) depending on BCG failure classification.

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

Evolving immunotherapy strategies in urothelial cancer. [2019] The treatment of nonmuscle-invasive urothelial carcinoma with bacillus Calmette-Guérin (BCG) represents the importance of immunotherapy in the treatment of cancer. Despite its clinical efficacy, up to 30% of patients will ultimately experience progression to muscle-invasive disease. This, along with an improved understanding of the biologic pathways involved, has led to efforts to improve, enhance, or alter the immune response in the treatment of urothelial carcinoma. A number of novel therapeutic approaches currently are being pursued, including recombinant BCG to induce T helper type 1 (Th1) immune responses, nonlive Mycobacterium agents, targeted agents toward cancer-associated antigens, immune-modulating vaccines, and adoptive T-cell therapies. Here, we review the current and future immunotherapy treatment options for patients with urothelial cancer.

3. Canada pubmed.ncbi.nlm.nih.gov

Salvage therapy for BCG failure with intravesical sequential gemcitabine and docetaxel in patients with recurrent NMIBC. [2023] Bacillus Calmette-Guérin (BCG) failure occurs in approximately 40% of patients with non-muscle-invasive bladder cancer (NMIBC) within two years. We describe our institutional experience with sequential intravesical gemcitabine and docetaxel (gem/doce) as salvage therapy post- BCG failure in patients who were not candidates for or declined radical cystectomy (RC).

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

Intravesical sequential gemcitabine and docetaxel versus bacillus calmette-guerin (BCG) plus interferon in patients with recurrent non-muscle invasive bladder cancer following a single induction course of BCG. [2022] Repeat BCG induction remains an option for select non-muscle invasive bladder cancer (NMIBC) patients who fail initial therapy. Alternative salvage intravesical regimens such as Gemcitabine and Docetaxel (Gem/Doce) have been investigated. We aimed to compare the efficacy BCG plus interferon a-2b (BCG/IFN) and Gem/Doce in patients with recurrent NMIBC after a single prior BCG course.

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

Sequential intravesical gemcitabine and docetaxel therapy in patients with nonmuscle invasive bladder cancer: a systematic review and meta-analysis. [2023] Shortages in intravesical Bacillus Calmette-Guérin (BCG) immunotherapy represent a challenge in the management of high-risk nonmuscle invasive bladder cancer (HR-NMIBC). This study aimed to review the efficacy and safety of intravesical gemcitabine (GEM) and docetaxel (DOCE) for BCG-naive and unresponsive HR-NMIBC.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Quality of Life, Efficacy, and Safety of Sequential Intravesical Gemcitabine + Docetaxel versus BCG for Non-Muscle Invasive Urinary Bladder Cancer: A Pilot Study. [2022] Bacille Calmette-Guerin (BCG) is considered the most effective agent for non-muscle invasive bladder cancer (NMIBC). However, due to BCG-related toxicity, multiple studies have suggested the role of newer chemotherapeutic drugs. The aim of our study was to evaluate intravesical gemcitabine + docetaxel (Gem/Doce) versus BCG with respect to quality of life (QOL), safety, and efficacy in NMIBC.

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

Intravesicle gemcitabine in management of BCG refractory superficial TCC of urinary bladder-our experience. [2022] The incidence of bladder malignancy is increasing worldwide and the projected rise is 28% by 2010 for both sexes (according to the WHO). Though intravesical adjuvant therapy with bacillus Calmette-Guérin (BCG) is superior to any other immunotherapeutic/chemotherapeutic agent in reducing tumor recurrences and disease progression, its real efficacy remains controversial as one-third of the patients will soon develop BCG failure. Hence, there is a need for an alternative intravesical agent for treatment of BCG failure. Our aim is to study the efficacy, tolerability, and safety of intravesical gemcitabine in managing BCG refractory superficial bladder malignancy.

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

Comparison of Side Effects and Tolerability Between Intravesical Bacillus Calmette-Guerin, Reduced-Dose BCG and Gemcitabine for Non-Muscle Invasive Bladder Cancer. [2022] To compare patient-reported side effects and tolerability of full-dose Bacillus Calmette-Guérin (BCG), reduced-dose BCG, and gemcitabine one week after administration.

9. England pubmed.ncbi.nlm.nih.gov

High grade superficial (G3t1) transitional cell carcinoma of the bladder treated with intravesical Bacillus Calmette-Guerin (BCG). [2006] Immunotherapy with Bacillus Calmette Guerin (BCG) has been widely used recently as primary option for treatment of high grade superficial (G3T1) carcinoma of the bladder. We describe our long term experience of therapy of G3T1 bladder cancer.

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

Weekly mitomycin C followed by monthly bacillus Calmette-Guerin or alternating monthly interferon-alpha2B and bacillus Calmette-Guerin for prophylaxis of recurrent papillary superficial bladder carcinoma. [2018] We evaluated alternatives to bacillus Calmette-Guerin (BCG) monotherapy using a new combination of chemotherapy and immunotherapy for recurrent superficial bladder carcinoma.