Acupuncture for the Treatment of Intravesical BCG-Related Adverse Events in High-Risk Non-muscle Invasive Bladder Cancer

Study Overview
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Brief Summary
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This phase II trial studies the safety and feasibility of utilizing acupuncture in patients with high-risk bladder cancer that has not spread to the surrounding muscle (non-muscle invasive) undergoing treatment with Intravesical BCG. BCG is a weakened form of the bacterium Mycobacterium bovis that does not cause disease. It is used in a solution to stimulate the immune system in the treatment of bladder cancer. Unfortunately, many patients experience side effects such as pelvic pain, painful urination, severe urgency, frequency, urge incontinence, need to urinate at night, and/or infectious complications. These side effects may cause patients to delay or stop BCG treatment. Acupuncture is a medical intervention in which fine metallic needles are inserted into anatomical locations of the body to stimulate the peripheral and the central nervous system. Giving acupuncture before each intravesical BCG treatment may help to reduce the side effects of intravesical BCG, and help patients complete treatment. Specific outcomes of interest include acceptability to patients, effect of acupuncture on intravesical BCG-related side effects, and adverse events associated with acupuncture.

Detailed Description
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OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo acupuncture therapy and receive BCG via intravesical injection on days 1, 8, 15, 22, 29, and 36 in the absence of unacceptable toxicity. Patients also receive standard of care symptom management. ARM II: Patients receive BCG via intravesical injection on days 1, 8, 15, 22, 29, and 36 in the absence of unacceptable toxicity. Patients also receive standard of care symptom management. Patients may undergo acupuncture therapy after completion of intravesical BCG therapy. After completion of study, patients are followed up at 1 week.

Official Title
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Acupuncture vs. Standard of Care for Induction Intravesical BCG-Related Adverse Events in High-Risk Non-Muscle Invasive Bladder Cancer

Conditions
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Bladder Urothelial Carcinoma In Situ, Recurrent Bladder Urothelial Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage 0is Bladder Cancer AJCC v8, Stage I Bladder Cancer AJCC v8, Superficial Bladder Urothelial Carcinoma

Intervention / Treatment
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* Device: Acupuncture Therapy
* Biological: BCG Solution
* Other: Best Practice
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: English-speaking Diagnosis of American Urological Association (AUA) high-risk non-muscle invasive bladder cancer (NMIBC), including high grade (HG) pT1 (invading only the lamina propria of the bladder), recurrent HG pTa (superficial tumors), HG pTa > 3 cm in size or multifocal, any carcinoma in situ, any variant histology, any lymphovascular invasion, and HG prostatic urethral involvement Diagnosis with urothelial carcinoma (primary histologic subtype), localized to the bladder, in the absence of nodal or other visceral metastases Patients who have been indicated for induction intravesical BCG in shared-decision-making with their primary urologist Have not received acupuncture in the previous 3 months Access to phone for study contacts Willing and able to participate in trial activities Platelets: 20,000/ uL or greater Absolute neutrophil count (ANC): 500 cells/uL or greater Able to understand and willing to sign written informed consent in English Exclusion Criteria: Subjects who have had intravesical or systemic chemotherapy or radiation therapy for bladder cancer or for other malignancies prior to entering the study Subjects who are indicated to receive other intravesical agents or therapies concurrently with BCG will be excluded Subjects who have muscle-invasive bladder cancer, radiographic evidence of lymph node metastases or metastatic disease involving other organs including brain metastases Patients with predominant histology other than urothelial carcinoma of the bladder who would not otherwise be considered candidates for BCG BCG is contraindicated in: Patients who are pregnant or lactating Patients with active tuberculosis Immunosuppressed patients with congenital or acquired immune deficiency, whether due to concurrent disease (e.g. acquired immunodeficiency syndrome [AIDS], lymphoma, leukemia), concomitant cancer therapy (cytotoxic drugs, radiation), or immunosuppressive therapy (e.g. corticosteroids, disease-modifying anti-rheumatic drugs [DMARDs]) Symptomatic urinary tract infection Febrile illness Patients requiring chronic treatment with certain antibiotics that may interfere with the effectiveness of BCG Any previous allergies or severe reactions to BCG Not pregnant or trying to become pregnant. Acupuncture points included in the protocol are contraindicated with pregnancy Does not have a pacemaker. There is potential of electrostimulation interfering with the operation and function of pacemakers Patients requiring chronic treatment with certain antibiotics that may interfere with the effectiveness of BCG. Fluoroquinolone therapy may decrease the efficacy of intravesical BCG. Antibiotic therapy for ongoing treatment of active tuberculosis will decrease the efficacy of intravesical BCG Uncontrolled or concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded. Acupuncture points included in the protocol are contraindicated with pregnancy and BCG is contraindicated in pregnancy Pacemaker. Patients with pacemakers are restricted due to the potential of electrostimulation interfering with a pacemakers operation Platelets: < 20,000/ uL. Risk of bleeding with acupuncture ANC: < 500 cells/uL. Risk of infection with acupuncture Received acupuncture in the previous 3 months. Acupuncture treatment effects persist after a course of treatment, previous exposure to the intervention has the potential to affect the baseline data for treatment and control arms

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (acupuncture, BCG)<br>Patients undergo acupuncture therapy and receive BCG via intravesical injection on days 1, 8, 15, 22, 29, and 36 in the absence of unacceptable toxicity. Patients also receive standard of care symptom management. | Device: Acupuncture Therapy<br>* Undergo acupuncture therapy<br>* Other names: Acupuncture;Biological: BCG Solution<br>* Given by intravesical injection<br>* Other names: TICE BCG Solution;Other: Best Practice<br>* Receive standard of care symptom management<br>* Other names: standard therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Arm II (BCG, standard of care)<br>Patients receive BCG via intravesical injection on days 1, 8, 15, 22, 29, and 36 in the absence of unacceptable toxicity. Patients also receive standard of care symptom management. Patients may undergo acupuncture therapy after completion of intravesical BCG therapy. | Device: Acupuncture Therapy<br>* Undergo acupuncture therapy<br>* Other names: Acupuncture;Biological: BCG Solution<br>* Given by intravesical injection<br>* Other names: TICE BCG Solution;Other: Best Practice<br>* Receive standard of care symptom management<br>* Other names: standard therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trial recruitment (proportion enrolled versus eligible, reason for not enrolling) | Will be described via qualitative report. | Up to 1 week after completion of treatment | 
| Trial retention (proportion retained versus all enrolled, reason for not completing) | Will be described via qualitative report. Successful retention is defined as continued participation within the trial until 1 week following completion of induction. | Baseline, up to 1 week after completion of treatment | 
| Protocol adherence (proportion adhered versus all enrolled, specifics for how protocol was not followed and why) | Will be described via qualitative report. Protocol adherence is defined as completion of the acupuncture interventions and follow-up surveys if randomized to the acupuncture arm or completion of the follow-up surveys if randomized to the control arm. | Up to 1 week after completion of treatment | 
| Patient satisfaction | Patients' responses to the Cancer Care Satisfaction survey at 3 weeks and at the conclusion of induction Bacillus Calmette-Guerin (BCG) between two arms will be compared using t-test. | At 3 weeks and after completion of treatment | 
| Clinic staff's responses to surveys | Clinic staff's responses to surveys assessing the healthcare burden of this protocol and time spent undergoing the acupuncture therapy for the experimental arm will be described via qualitative report | Up to 1 week after completion of treatment | 
| Incidence of adverse events | Adverse events associated with acupuncture therapy in the experimental arm will be described via qualitative report. | Up to 1 week after completion of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BCG instillation adherence (out of a possible planned six treatments) | BCG instillation adherence (out of a possible planned six treatments (successful adherence defined as the number of successfully administered BCG instillations (of a possible 6 total), treatment interruptions (defined as number of weeks that a BCG instillation was delayed), weeks missed (measured as any vs none, and total weeks that BCG was not administered of the planned 6 weekly induction doses of intravesical BCG), intravesical BCG dwell times (measured in minutes), and requirement for dose reductions (measured as yes/no) between the acupuncture and control arms will be compared via t-test and chi-square as appropriate. | Up to 1 week after completion of treatment | 
| Bladder and bowel symptoms as self reported by patients | Compare the responses of patients in the experimental and control arms to the European Organization for Research and Treatment of Cancer - Non-Muscle Invasive Bladder Cancer 24 (EORTC-NMIBC24) symptom index, which was specifically designed to assess bladder and bowel symptoms for patients with NMIBC including assessments of impact of intravesical therapy. | From week 1 to week 6 of treatment | 
| Quality of life: EORTC-QLQ-C30 | Assessed using the EORTC Health and Quality of Life Rating Scale (EORTC-QLQ-C30). | From week 1 to week 6 of treatment | 
| Median weekly pill counts of medications prescribed for the management of BCG-related side effects, standardized by dosage across medication types | Will be compared via Wilcoxon rank sum test. | Up to 1 week after completion of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urinary Bladder