Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Behaviors and Mental Disorders

Rare Diseases

Recurrence

Carcinoma

Carcinoma, Transitional Cell

Carcinoma in Situ

Urinary Bladder Neoplasms

Urinary Bladder Diseases

Non-Muscle Invasive Bladder Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urologic Diseases

Male Urogenital Diseases

Quality of Life

Transitional Cell Carcinoma

Patients with non-muscle invasive bladder cancer who underwent one of the following endoscopic resection surgeries : TURBK, MAPPING, TURBK SECOND LOOK, BLADDER BIOPSIES

Francesco Montorsi, MD

Giusy Burgio, MSc

A database has been created and will be used in which data will be collected in electronic format relating to adult patients who underwent one of the following endoscopic resection surgeries: TURBK, MAPPING, TURBK SECOND LOOK, BLADDER BIOPSIES.

Each patient will be followed for approximately 10 years starting from the date of surgery. The patient may be contacted for yearly follow-up through one of the preferred methods indicated (phone call, email or home address) which will be carried out by the staff of the Urology Department. The data for each patient will then be transferred to the database itself. The data collected will be handled follwing the most strict GCPs and privacy norms.

The data entered will concern:

* period before hospitalization (symptoms, clinical data) and completion of a pre-surgery questionnaire
* hospitalization period with all its related data
* questionnaires relating to quality of life which will be administered to the patient once a year according to the preferred method expressed by the patient in the informed consent.

Study on the Occurrence of Possible Relapses and on the Quality of Life in Patients Who Underwent TURBK.

Observational Study on the Occurrence of Possible Relapses and on the Quality of Life in Patients Who Underwent Endoscopic Resection Surgery for Bladder Cancer (TURBK).

All patients, before underwent endoscopic resection surgery, receive a diary in which we ask a detailed clinical history of the patient with their symptoms, diagnosis and previous urological e non urological treatments performed before the operation. A detailed intraoperative, postoperative and follow-up clinical history

Through the collection of a detailed clinical history of the patient in which themselves report symptoms, diagnosis and previous urological and non-urological treatments and also through the medical record.

IRCCS San Raffaele

Professor

Pharmaceutical Solutions

All Drugs and Chemicals

BCG Vaccine

Vaccines

Adjuvants, Immunologic

Immunologic Factors

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.

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.

Acupuncture Therapy

BCG Solution

Receive standard of care symptom management

Best Practice

Quality-of-Life Assessment

Questionnaire Administration

Sarah P. Psutka

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.

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.

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

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

Will be described via qualitative report.

Will be described via qualitative report. Successful retention is defined as continued participation within the trial until 1 week following completion of induction.

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.

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 assessing the healthcare burden of this protocol and time spent undergoing the acupuncture therapy for the experimental arm will be described via qualitative report

BCG related adverse events compared between patients receiving acupuncture and patients receiving standard of care.

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.

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.

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.

Will be compared via Wilcoxon rank sum test.

National Cancer Institute (NCI)

Fred Hutchinson Cancer Center

Associate Professor

Toxicity or AEs related to BCG administration were collected by patient survey on a weekly basis using the CTCAE v.50 assessment of Systemic Therapy Toxicity. Patients in the acupuncture arm were surveyed weekly prior to acupuncture treatments regarding side effects and potential adverse events associated with the acupuncture intervention using the CTCAE v5. There were two acupuncture-related adverse events: 1 patient reporting a Grade 1 bruise and 1 patient reporting a Grade 1 pain.

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.

Acupuncture Therapy: Undergo acupuncture therapy

BCG Solution: Given by intravesical injection

Best Practice: Receive standard of care symptom management

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Arm I (Acupuncture, BCG)

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.

Acupuncture Therapy: Undergo acupuncture therapy

BCG Solution: Given by intravesical injection

Best Practice: Receive standard of care symptom management

Quality-of-Life Assessment: Ancillary studies

Questionnaire Administration: Ancillary studies

Arm II (BCG, Standard of Care)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Smoking Status

Pathologic stage Ta: Presence of a papillary tumor that does not infiltrate the bladder wall. Tis: The existence of carcinoma in situ, which constitutes a non-invasive flat high-grade (G3) cancer. T1: Tumor penetration into the connective tissue beneath the surface lining. All other stages were excluded. Ta is the least aggressive, and Tis and T1 are the most aggressive. Please note these were not outcomes, but were inclusion criteria for patients who would be eligible to receive induction BCG and therefore would be candidates for study entry.

Tumor stage

"The Charlson Comorbidity Index (CCI) was a method of categorizing comorbidities of patients based on the International Classification of Diseases diagnosis. The CCI score ranged from 0 (better outcome) to 21 (worse outcome). The higher the score, the more fragile/ill the patient was."

Charlson Comorbidity Index

Eastern Cooperative Oncology Group (ECOG) performance status criteria is used to assess how a patient's disease is progressing and to assess how the disease affects the daily living abilities of the patient. The scores on this instrument range from 0-5 (0=fully active and 5=dead), with higher scores indicating poorer performance.

Eastern Cooperative Oncology Group (ECOG) performance status

Some patients signed the consent but couldn't start the treatment because of progression of disease, those data were not collected.

Dr. Sarah Psutka, MD, MS

Total number screened for trial eligibility

Screened for Trial Eligibility

Trial Recruitment: Number of Participants Eligible, Enrolled, and Not Enrolled

Trial Retention (Proportion Retained Versus All Enrolled, Reason for Not Completing)

Protocol Adherence (Proportion Adhered Versus All Enrolled, Specifics for How Protocol Was Not Followed and Why)

Patient Satisfaction

Clinic Staff's Responses to Surveys

Bowel Symptoms

Fatigue

Flu-like Symptoms

Headache

Hematuria

Other

Pain

Urinary Symptoms

The number of AEs are not mutually exclusive and participants may have reported more than one AE

Number of Adverse Events

This p value relates to instillation adherence

Instillation adherence

Missed visits

BCG Instillation Adherence (Out of a Possible Planned Six Treatments)

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Constipation Symptoms.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Diarrhea Symptoms.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Urinary Symptoms.

Constipation Symptoms

Diarrhea Symptoms

Bladder and Bowel Symptoms as Self Reported by Patients

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Global Health.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Physical Function.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Emotional Function.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Social Function.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Fatigue Symptoms.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Pain Symptoms.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Malaise Symptoms.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Role Function.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Cognitive Function.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Nausea Symptoms.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Dyspnoea Symptoms.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Insomnia Symptoms.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Appetite Loss Symptoms.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Finances.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Intravesical Symptoms.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Worries.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Bloating Symptoms.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Sexual Function.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Male Sex Problems.

For the patient survey, the two arms will be compared using chi-squared. This analysis is for Intimacy.

Global Health Organization

Physical Function

Emotional Function

Social Function

Fatigue Symptoms

Pain Symptoms

Malaise Symptoms

Role Function

Cognitive Function

Nausea Symptoms

Dyspnoea Symptoms

Insomnia Symptoms

Appetite Loss Symptoms

Finances

Intravesical Symptoms

Worries

Bloating Symptoms

Sexual Function

Male Sex Problems

Intimacy

Quality of Life: EORTC-QLQ-C30

Median Weekly Pill Counts of Medications Prescribed for the Management of BCG-related Side Effects, Standardized by Dosage Across Medication Types

Overall Study

Antineoplastic Agents

Gemcitabine

Pembrolizumab

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

INDUCTION: Patients receive pembrolizumab IV over 25-40 minutes on day 1 of cycles 1-4. Patients also receive gemcitabine hydrochloride intravesically on days 1, 8 and 15 of cycles 1 and 2. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning cycle 5, patients with no evidence of disease after induction receive pembrolizumab IV over 25-40 minutes and gemcitabine intravesically on day 1. Treatment repeats every 3 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity.

Gemcitabine Hydrochloride

Site Public Contact

Charles C. Peyton

Nicholas DiBella

Shahzad Siddique

Marc Dall'Era

Lambros Stamatakis

Paul L. Crispen

Jeffrey L. Berenberg

John M. Schallenkamp

Bryan A. Faller

Michael E Woods

This phase II trial studies the effect of adding pembrolizumab to gemcitabine in treating patients with non-muscle invasive bladder cancer whose cancer does not respond to Bacillus Calmette-Guerin (BCG) treatment. Chemotherapy drugs, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the patient's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding pembrolizumab to gemcitabine may delay the return of BCG-unresponsive bladder cancer for longer period compared to gemcitabine alone.

PRIMARY OBJECTIVES:

I. Estimate the 6-month complete response rate of treatment with intravesical gemcitabine hydrochloride (gemcitabine) in combination with MK-3475 (pembrolizumab) in patients with Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) that have a carcinoma in situ (CIS) component.

II. Estimate the 18 month event-free survival (EFS) rate for all patients with BCG-unresponsive NMIBC receiving intravesical gemcitabine in combination with MK-3475 (pembrolizumab).

SECONDARY OBJECTIVES:

I. To characterize the safety profile of the combination of intravesical gemcitabine with MK-3475 (pembrolizumab) with BCG-unresponsive NMIBC (CIS or high grade Ta and T1 with or without a CIS component).

II. To estimate progression-free survival (PFS) of patients with BCG-unresponsive NMIBC treated with intravesical gemcitabine in combination with MK-3475 (pembrolizumab).

III. To estimate overall survival (OS) of patients with BCG-unresponsive NMIBC treated with intravesical gemcitabine in combination with MK-3475 (pembrolizumab).

IV. To estimate cystectomy-free survival of patients with BCG-unresponsive NMIBC treated with intravesical gemcitabine in combination with MK-3475 (pembrolizumab).

V. To estimate recurrence-free survival (RFS) for patients with a CIS component only and those without a CIS component.

EXPLORATORY OBJECTIVES:

I. To assess correlation between tumor mutation burden (TMB) and EFS and 6-month complete response (CR) rate.

II. To assess correlation between specific genomic alterations (single nucleotide variant \[SNV\] and copy number gains/loss) and EFS and 6-month complete response rate.

III. To assess correlation between APOBEC mutational signature and EFS and 6-month complete response rate.

IV. To assess correlation between immune gene signatures (IGS) and EFS and 6-month complete response rate.

V. To assess correlation between PD-L1 ribonucleic acid (RNA) levels and EFS and 6-month complete response rate.

VI. To assess correlation between RNA molecular subtype and EFS and 6-month complete response rate.

VII. To assess correlation between intratumoral T-cell receptor (TCR) clonality and EFS and 6-month complete response rate.

VIII. To assess correlation between changes in peripheral blood TCR clonality and EFS and 6-month complete response rate.

IX. To assess EFS in patients with urine cell free deoxyribonucleic acid (DNA) (cfDNA) + versus (vs.) patients with cfDNA.

OUTLINE:

INDUCTION: Patients receive pembrolizumab intravenously (IV) over 25-40 minutes on day 1 of cycles 1-4. Patients also receive gemcitabine hydrochloride intravesically on days 1, 8 and 15 of cycles 1 and 2. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning cycle 5, patients with no evidence of disease after induction receive pembrolizumab IV over 25-40 minutes and gemcitabine intravesically on day 1. Treatment repeats every 3 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients with evidence of disease (recurrence or progression) or stop study treatment to receive non-protocol treatment during induction are followed up every 6 months for 5 years. Patients who go off treatment due to any reason other than recurrence/progression or receiving subsequent non-protocol treatment during induction will go to clinical follow-up until evidence of disease progression/recurrence. Thereafter, patients are followed up every 6 months until 5 years from registration. Patients who complete scheduled maintenance treatment according to protocol therapy are followed up every 3 months for 2 years and then every 6 months for 3 years until disease progression/recurrence or receiving subsequent non-protocol treatment. Thereafter, patients are followed up every 6 months until 5 years from registration. Patients who have evidence of disease during maintenance therapy are followed up every 6 months until 5 years from registration.

Testing the Addition of an Anti-cancer Drug, Pembrolizumab, to the Usual Intravesical Chemotherapy Treatment (Gemcitabine) for the Treatment of BCG-Unresponsive Non-muscle Invasive Bladder Cancer

Phase II Trial of Intravesical Gemcitabine and MK-3475 (Pembrolizumab) in the Treatment of Patients With BCG-Unresponsive Non-Muscle Invasive Bladder Cancer

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

A complete response, only for patients with a CIS component, is a cystoscopy without evidence of bladder tumor and negative biopsy (including directed biopsies to any suspicious areas and in addition random bladder biopsies including trigone, left lateral wall, right lateral wall, posterior bladder, dome of bladder, and the prostatic urethra in men), and negative cytology for high grade disease.

For patients without a documented event and who are still alive, they will be censored at last disease assessment. For patients who start any subsequent ant-cancer therapy without any reported events will be censored at their last disease assessment. will be obtained with a Kaplan-Meier estimator (using the Greenwood formula to estimate the variance) for the entire 153 patient group consisting of patients with CIS, CIS with Ta/T1 or Ta or T1 disease. A 90% confidence interval will be generated for the 18-month EFS estimate.

Adverse events will be assessed based on the National Cancer Institute (NCI) common toxicity criteria (Common Terminology Criteria for Adverse Events \[CTACAE\] version \[v\] 5.0).

Analysis will only include those patients in the CIS population who achieve a response. Patients who are alive and without a documented progression at the time of analysis will be censored at the time of the last disease status evaluation. The Kaplan-Meier product-limit estimator will be used to estimate DOR, medians and 95% confidence intervals (CI).

Surviving patients without any documented progressions will be censored at the date of last known contact. Progression will be defined as the development of muscle invasive bladder cancer or metastatic urothelial cancer (nodal and/or distant). The Kaplan-Meier product-limit estimator will be used to estimate PFS, medians and 95% CI.

Surviving patients will be censored at the date of last known contact. The Kaplan-Meier product-limit estimator will be used to estimate OS, medians and 95% CI.

The Kaplan-Meier product-limit estimator will be used to estimate cystectomy-free survival, medians and 95% CI.

Surviving patients without any documented recurrence will be censored at the date of last known contact. Recurrence will be defined as the development of high-grade bladder cancer for patients with a CIS component only and those without a CIS component. The Kaplan-Meier product-limit estimator will be used to estimate RFS, medians and 95% CI.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study on the Occurrence of Possible Relapses and on the Quality of Life in Patients Who Underwent TURBK.	NCT06167356	Non Muscle Inva... Non-Muscle Inva... Non-Muscle Inva... Bladder Cancer Bladder Disease Bladder Neoplas... Bladder Urothel... Bladder Cancer ... Bladder Cancer ... Bladder Urothel... Bladder Urothel...		18 Years -	IRCCS San Raffaele
Acupuncture for the Treatment of Intravesical BCG-Related Adverse Events in High-Risk Non-muscle Invasive Bladder Cancer	NCT04496219	Bladder Urothel... Recurrent Bladd... Stage 0a Bladde... Stage 0is Bladd... Stage I Bladder... Superficial Bla...	Acupuncture The... BCG Solution Best Practice Quality-of-Life... Questionnaire A...	18 Years -	Fred Hutchinson Cancer Center
Testing the Addition of an Anti-cancer Drug, Pembrolizumab, to the Usual Intravesical Chemotherapy Treatment (Gemcitabine) for the Treatment of BCG-Unresponsive Non-muscle Invasive Bladder Cancer	NCT04164082	Bladder Urothel... Invasive Bladde... Stage 0a Bladde... Stage 0is Bladd... Stage I Bladder...	Gemcitabine Hyd... Pembrolizumab	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for bladder urothelial carcinoma in situ