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

Phase 2

Completed

• Conditions: Recurrent Bladder Urothelial Carcinoma; Stage 0is Bladder Cancer AJCC v8; Bladder Urothelial Carcinoma In Situ; Stage 0a Bladder Cancer AJCC v8; Stage I Bladder Cancer AJCC v8; Superficial Bladder Urothelial Carcinoma
• Interventions: Device: Acupuncture Therapy; Biological: BCG Solution; Other: Best Practice; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

• Registration Number: NCT04496219
• Lead Sponsor: Fred Hutchinson Cancer Center

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-07-29
• Study First Submitted QC: 2020-07-29
• Study First Posted: 2020-08-03
• Study Start: 2021-01-22
• Primary Completion: 2022-08-16
• Study Completion: 2022-08-23
• Results First Submitted: 2023-08-15
• Status Verified: 2023-12
• Results First Submitted QC: 2023-12-13
• Last Update Submitted: 2023-12-13
• Results First Posted: 2024-01-02
• Last Update Posted: 2024-01-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (acupuncture, BCG)	Acupuncture Therapy	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 I (acupuncture, BCG)	Quality-of-Life Assessment	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 I (acupuncture, BCG)	Questionnaire Administration	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 (BCG, standard of care)	Best Practice	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.
Arm I (acupuncture, BCG)	BCG Solution	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 (BCG, standard of care)	Acupuncture Therapy	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.
Arm I (acupuncture, BCG)	Best Practice	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 (BCG, standard of care)	BCG Solution	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.
Arm II (BCG, standard of care)	Quality-of-Life Assessment	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.
Arm II (BCG, standard of care)	Questionnaire Administration	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.

Primary Outcome Measures

Name	Time	Method
Protocol Adherence (Proportion Adhered Versus All Enrolled, Specifics for How Protocol Was Not Followed and Why)	Up to 1 week after completion of treatment, an average of 7 weeks	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.
Patient Satisfaction	At 3 weeks and after completion of treatment, an average of 7 weeks	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.
Clinic Staff's Responses to Surveys	Up to 1 week after completion of treatment, an average of 7 weeks	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
Number of Adverse Events	Up to 1 week after completion of treatment, an average of 7 weeks	BCG related adverse events compared between patients receiving acupuncture and patients receiving standard of care.
Trial Recruitment: Number of Participants Eligible, Enrolled, and Not Enrolled	Up to 1 week after completion of treatment, an average of 7 weeks	Will be described via qualitative report.
Trial Retention (Proportion Retained Versus All Enrolled, Reason for Not Completing)	Baseline, up to 1 week after completion of treatment, an average of 7 weeks	Will be described via qualitative report. Successful retention is defined as continued participation within the trial until 1 week following completion of induction.

Secondary Outcome Measures

Name	Time	Method
BCG Instillation Adherence (Out of a Possible Planned Six Treatments)	Up to 1 week after completion of treatment, an average of 7 weeks	BCG instillation adherence (successful adherence defined as the number of successfully administered BCG instillations of a possible 6 total) and weeks missed (measured as total weeks that BCG was not administered of the planned 6 weekly induction doses of intravesical BCG). Results between the acupuncture and control arms will be compared via t-test.
Bladder and Bowel Symptoms as Self Reported by Patients	From week 1 to week 6 of treatment	Assessed using the EORTC - 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. All of the subscales and single-item measures range in score from 0 to 100 and a high scale score represents a higher response level (ranging from 0 = low to 100 = high/healthy level of function; from 0 = low to 100 = high quality-of-life; from 0 = low to 100 = high level of symptomatology/problems). Subscale scores are each calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100.
Quality of Life: EORTC-QLQ-C30	From week 1 to week 6 of treatment	Assessed using the EORTC Health and Quality of Life Rating Scale (EORTC-QLQ-C30). All of the subscales and single-item measures range in score from 0 to 100 and a high scale score represents a higher response level (ranging from 0 = low to 100 = high/healthy level of function; from 0 = low to 100 = high quality-of-life; from 0 = low to 100 = high level of symptomatology/problems). Subscale and global health status scores are each calculated by transforming individual item scores into a 0 to 1 scale, taking the mean, and multiplying by 100.
Median Weekly Pill Counts of Medications Prescribed for the Management of BCG-related Side Effects, Standardized by Dosage Across Medication Types	Up to 1 week after completion of treatment, an average of 7 weeks	Will be compared via Wilcoxon rank sum test.

Trial Locations

Locations (1)

Fred Hutch/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States