Clinical trial NCT04496219: Acupuncture for the Treatment of Intravesical BCG-Related Adverse Events in High-Risk Non-muscle Invasive Bladder Cancer
Official title: Acupuncture vs. Standard of Care for Induction Intravesical BCG-Related Adverse Events in High-Risk Non-Muscle Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Keywords: Urinary Bladder
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-08-03
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Trial Recruitment: Number of Participants Eligible, Enrolled, and Not Enrolled
timeFrame: Up to 1 week after completion of treatment, an average of 7 weeks
measure: Trial Retention (Proportion Retained Versus All Enrolled, Reason for Not Completing)
timeFrame: Baseline, up to 1 week after completion of treatment, an average of 7 weeks
measure: Protocol Adherence (Proportion Adhered Versus All Enrolled, Specifics for How Protocol Was Not Followed and Why)
timeFrame: Up to 1 week after completion of treatment, an average of 7 weeks
measure: Patient Satisfaction
timeFrame: At 3 weeks and after completion of treatment, an average of 7 weeks
measure: Clinic Staff's Responses to Surveys
timeFrame: Up to 1 week after completion of treatment, an average of 7 weeks
measure: Number of Adverse Events
timeFrame: Up to 1 week after completion of treatment, an average of 7 weeks
Secondary outcomes:
measure: BCG Instillation Adherence (Out of a Possible Planned Six Treatments)
timeFrame: Up to 1 week after completion of treatment, an average of 7 weeks
measure: Bladder and Bowel Symptoms as Self Reported by Patients
timeFrame: From week 1 to week 6 of treatment
measure: Quality of Life: EORTC-QLQ-C30
timeFrame: From week 1 to week 6 of treatment
measure: Median Weekly Pill Counts of Medications Prescribed for the Management of BCG-related Side Effects, Standardized by Dosage Across Medication Types
timeFrame: Up to 1 week after completion of treatment, an average of 7 weeks
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Sarah P. Psutka
role: PRINCIPAL_INVESTIGATOR
References: