Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Pharmaceutical Solutions

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Analgesics

Aldesleukin

Interleukin-2

BCG Vaccine

Vaccines

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Adjuvants, Immunologic

Immunologic Factors

CMM patients will received 4 treatments of intralesional Interleukin-2 two weeks apart over an eight week period.

CMM patients will receive 4 treatments of combination therapy intralesional Interleukin-2 and Bacillus Calmette Guerin two weeks apart over an eight week period.

IL-2 is prepared as 4 million International Units (IU) per 0.8ml at a total dose of 500,000 IU in 0.1ml of sterilized saline (0.9%, m/v)/lesion.

BCG (OncoTICE solutions 1-8 x 10-8 Colony Forming Units (CFU)) will be administered at a maximum dose of 3.2 million CFU per treatment at a maximum of 1.6 million CFU per lesion (max 2 lesions).

IL-2 is prepared as 4 million International Units (IU) per 0.8ml at a total dose of 500,000 IU in 0.1ml of sterilized saline (0.9%, m/v)/lesion (in remaining lesions).

Combination therapy Interleukin-2 and Bacillus Calmette Guerin

Carman A Giacomantonio, MD

The investigators aim to include 100 local participants over the next 5 years in a two-stage sequential randomized interventional study of intralesional Interleukin-2 (IL-2) and Bacillus Calmette Guerin (BCG) to assess the utility of treating cutaneous metastatic melanoma (CMM).

In the first stage of the study, all consenting CMM patients will be randomized and will receive 4 treatments of either intralesional IL-2 or intralesional IL-2 and BCG. We hypothesize that patients with MM (stage 3C or 4a with a minimum of 4 lesions) that receive combination therapy (IL-2/BCG) in the first stage of treatment will have a higher complete response (iCR) rate compared to IL-2 therapy alone.

Response to stage-one treatment will be monitored and patient response to treatment will be determined and reported according to Immune Response Evaluation Criteria in Solid Tumours (iRECIST) guidelines. Based on response to stage-one treatment, patients will be placed into a response group before entering stage two. For stage two of the trial, patients will be randomized again, and placed into a treatment group; Il-2, IL-2 and BCG, BCG, or Discontinue Treatment. Response to treatment will be monitored and patient response to treatment will be determined and reported according to iRECIST guidelines.

All patients will have lesions biopsied following standard surgical practice techniques and will provide urine and blood for analysis. Tissue samples will be assessed for immune system activity and transcriptome analysis, and urine and blood will be assessed for immune cell populations and markers. All patients will be followed for 5 years post treatment, and patient disease and survival status will be recorded according to iRECIST.

Patients will be randomized to first stage treatment and allocated to 1) IL-2 or 2) IL-2/BCG treatment. First stage treatment patients receive 4 treatments of 1) IL-2 or 2) IL-2 and BCG. Patient response will be determined for treatment groups following iRECIST guidelines as; 1) complete responder, 2) partial responder, or 3) stable disease. In second stage treatment, patients who completely respond to first stage treatment will be randomized to 1) discontinue treatment and followed every 3 mos for 2 yrs and then every 6 mos from yrs 3-5, or 2) will receive 2 additional treatments and then followed every 3 mos for 2 yrs and then every 6 mos from yrs 3-5. Patients that do not completely respond to first stage treatment, will be re-staged using a PET/CT scan. Patients not requiring escalation to systemic therapy will be randomized and advance to second stage treatment (IL-2, IL-2 and BCG, or BCG).

The Response to Intralesional IL-2 and/or BCG Treatment for Cutaneous Metastatic Melanoma

The primary outcome measure is the achievement of a superior response rate in patients receiving combination IL-2/BCG treatment compared to patients receiving IL-2 alone. Patient response to treatment will be monitored and patients will be categorized as 1) complete responders, 2) partial responders or 3) stable disease. Data will be analyzed by one-way ANOVA to compare proportion outcomes amongst treatment and response groups.

The achievement of a superior response rate in patients that partially respond or do not respond to single agent IL-2 in stage one, with the addition of BCG treatment in stage two. Patient response to treatment will be monitored and patients will be categorized as 1) complete responders, 2) partial responders or 3) stable disease. Data will be analyzed by one-way ANOVA to compare proportion outcomes amongst treatment and response groups.

Complete responders to stage-one treatments will be assessed to determine if there is a difference in overall survival between participants that continue treatment compared to participants that discontinue treatment. Data will be assessed using Kaplan-Meier methods and compared using Log-rank tests.

Response groups following stage-two treatments will be assessed to determine if there is a difference in overall survival amongst response groups. Data will be assessed using Kaplan-Meier methods and compared using Log-rank tests.

All patients will be followed every 3 months for 2 years and then biannual assessments for years 3-5 after the initial intervention to assess the number of stable or new lesions amongst treatment response groups. Number (integer value) of new metastases will be recorded as a part of this assessment. Data will be compared using a one-way ANOVA. Post-Hoc analysis will be conducted when needed.

Assessment of Metastasis - All patients will be followed every 3 months for 2 years and then biannual assessments for years 3-5 after the initial intervention to assess change in lesion size according to iRECIST guidelines. Lesions will be measured in mm in 2 dimensions as part of this assessment. Data will be compared using a one-way ANOVA. Post-Hoc analysis will be conducted when needed.

Nova Scotia Health Authority

Carman Giacomantonio

Surgical Oncologist/General Surgeon/Professor

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

Non-Muscle Invasive Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Gemcitabine

Docetaxel

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Intravesical once a week for 6 consecutive weeks followed by monthly instillations during maintenance for 2 years

intravesical once a week for 6 consecutive weeks during induction followed by weekly instillations for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 months

Bacillus Calmette Guerin

Max Kates, MD

Site Public Contact

Charles C. Peyton

Nicholas DiBella

Chinedu Mmeje

Jay W. Carlson

Aditya Bagrodia

Siamak Daneshmand

Janet E. Kukreja

Lambros Stamatakis

Sunil H. Patel

Michael J. Whalen

Padraic O'Malley

John M. Schallenkamp

Parth Modi

Nicklas R. Pfanzelter

Marcus L. Quek

Howard M. Gross

Michael A. O'Donnell

Patrick J. Hensley

Mary E. Westerman

Stephen T. Ryan

Mark A. Preston

Jennifer Yates

Todd M. Morgan

Kevin Ginsburg

Lawrence M. Dagrosa

Eugene J. Pietzak

Nitin Yerram

Saum B. Ghodoussipour

The study hypothesis is that BCG naïve non-muscle invasive bladder cancer (NMIBC) patients treated with intravesical Gemcitabine + Docetaxel (GEMDOCE) will result in a non-inferior event-free survival (EFS) compared to standard treatment with intravesical BCG. The purpose of this study is to test whether Gemcitabine + Docetaxel is a better or worse treatment than the usual BCG therapy approach. The primary objective of this study is to determine the event free survival (EFS) of BCG-naïve high grade non-muscle invasive bladder cancer patients treated with intravesical BCG vs Gemcitabine + Docetaxel. Secondary objectives are as follows: to compare changes in cancer-specific and bladder cancer-specific QOL from baseline to treatment between BCG-naïve high grade NMIBC patients receiving BCG and GEMDOCE, to determine the cystectomy free survival (CFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE, to determine the progression free survival (PFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE, and to determine the safety and toxicity of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.

The primary objective of this study is to determine the event free survival (EFS) of BCG-naïve high grade non-muscle invasive bladder cancer patients treated with intravesical BCG vs Gemcitabine + Docetaxel. Secondary objectives are as follows: to compare changes in cancer-specific and bladder cancer-specific QOL from baseline to treatment between BCG-naïve high grade NMIBC patients receiving BCG and GEMDOCE, to determine the cystectomy free survival (CFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE, to determine the progression free survival (PFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE, and to determine the safety and toxicity of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE

Intravesical BCG vs GEMDOCE in NMIBC

A Randomized Phase III Trial of Intravesical BCG veRsus Intravesical Docetaxel and GEmcitabine Treatment in BCG Naïve High Grade Non-Muscle Invasive Bladder Cancer (BRIDGE)

To determine the event free survival (EFS) of BCG-naïve high grade non-muscle invasive bladder cancer (NMIBC) patients treated with intravesical BCG vs GEMDOCE.

To compare changes in cancer-specific QOL from baseline to treatment between BCG-naïve high grade NMIBC patients receiving BCG and GEMDOCE.

To determine the cystectomy free survival (CFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.

To determine the progression free survival (PFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE

To compare changes in bladder cancer-specific QOL from baseline to treatment between BCG-naïve high grade NMIBC patients receiving BCG and GEMDOCE.

National Cancer Institute (NCI)

ECOG-ACRIN Cancer Research Group

Immunomodulating Agents

Intradermal BCG Group (n=16): 0.1 ml of lyophilized, live, and attenuated BCG intradermal vaccine, containing between 2 and 8 x 1.000.000 C.F.U in a single dose.

Placebo group (n = 16): 0.9% saline solution in the same volume as BCG vaccine in a single dose.

0.1 ml of lyophilized, live, and attenuated BCG intradermal vaccine, containing between 2 and 8 x 1.000.000 C.F.U in a single dose.

0.1 ml 0.9% saline in the same volume as the BCG vaccine in a single dose.

PLACEBO

Leonardo O Reis, MD, PhD

Bladder cancer (BC) is one of the most common cancers worldwide and the most successful example of vaccine in cancer treatment, representing an efficient model for studying the importance of systemic and local immune mechanisms. Despite being the standard of treatment for the last 40 years, the exact mode of action of immunotherapy with the bacillus Calmette-Guérin (BCG) is still poorly defined. In a mechanistic study, the investigators intend to prospectively investigate immunological signatures, including immune-checkpoints, pre and post-treatment in patients with BC, and correlate the cytokines of the immune by-product and BCG administration pathway to understand the independent contributions of BCG priming (prior exposure to BCG) and crosstalk immunotherapy between tumor profiles and immune response of the patient. The proposed research strategy is justified by the need to identify subsets of patients who better respond to an intervention, or to predict why new immunotherapies and drugs may be successful or failed in clinical trials.

Recognizing patient-to-patient variability, key data scarcity, and insight into traditional reductionist therapy, the BCG model offers exceptionally compelling opportunities to understand how immune system behavior in health and disease emerges from local, systemic, genetic, epigenetic, cellular, and environmental modulating factors.

The application seeks to change the current clinical practice and research paradigms, by using new theoretical concepts, challenging bladder cancer patients with a highly effective, safe, and affordable immunotherapy, the gold standard in the last 40 years of NMIBC, and in light of new concepts and methodologies brought by the paradigm of immune-checkpoint inhibitors that justified the Nobel Prize in Physiology or Medicine in 2018.

The current proposal has the potential to impact the prognosis and identification of those who are unlikely to respond to immune-checkpoint inhibitors, scenarios in which important unanswered questions remain, particularly as this class of agents advances along the spectrum of non-metastatic disease.

In a mechanistic approach, patients diagnosed with NMIBC and with the indication for intravesical BCG treatment will be randomized to placebo versus a priming intradermic BCG 14 days before the intravesical treatment and followed up to 180 days.

The investigators will define important clinical paradigms:

1. The role of the priming effect on the immune system and better understanding of BCG immunotherapy, with a clear potential for improvement of bladder cancer treatment in NMIBC and MIBC scenarios;
2. The potential of BCG, a widely used vaccine, to improve or impair the results of new immunotherapies, given its long-lasting effect;
3. Rational to develop future treatment associations of BCG and immune-checkpoints. \\

Under the new immunological concepts, a better understanding of tumor-associated immune responses in BC patients could provide more informed clinical decisions and treatment optimization.

Considering the growing need of assessing the value of treatment at the expense of cost, part of our proposal strategy is to limit financial toxicity as an important issue in cancer treatment and new immunotherapies.

Immunological Response of Bladder Cancer Patients Under BCG

Systemic Immunological Response of Bladder Cancer Patients Under Bacillus Calmette Guérin Treatment

American Urological Association Symptom Score Questionnaire - minimum 0 and maximum 35, higher scores mean a worse outcome.

Coordination for the Improvement of Higher Education Personnel

Pontifical University Catholic of Campinas

University of Campinas, Brazil

Professor Livre Docente

Antibodies

Antibodies, Monoclonal

Immunoglobulins

PF-06801591 in combination with Bacillus Calmette Guerin(induction+maintenance).

PF-06801591 in combination with Bacillus Calmette Guerin (induction only).

Bacillus Calmette Guerin (induction and maintenance).

A monoclonal antibody (mAb) that blocks the interaction between PD-1 and PD-L1/PD-L2.

PF-06801591

Immunotherapy treatment approved by FDA for patients with high-risk non-muscle invasive bladder cancer

Bacillus Calmette-Guerin

Pfizer CT.gov Call Center

The purpose of this study is to learn about the safety and effects of the study medicine (sasanlimab) in people with non-muscle invasive bladder cancer. This study is seeking participants whose bladder cancer is still in early stages, has not spread outside of the bladder, has been removed with surgery, and is high risk (Part A) or was previously treated with BCG (Bacillus Calmette Guerin), a standard treatment for bladder cancer (Part B).

In Part A (enrollment closed), each participant was assigned to one of three study treatment groups.

* One group is given sasanlimab and BCG at the study clinic.
* The second group is given sasanlimab and BCG at the study clinic. This group will receive BCG for the first six weeks only.
* The third group is given BCG only and will not receive sasanlimab.

In Part B of the study, each new participant will be assigned to a study treatment group based on the type of their bladder tumor.

- Both groups will be given sasanlimab at the study clinic.

On August 31, 2022, the Sponsor announced the discontinuation of enrollment to Part B. The decision to discontinue enrollment to Part B was not made for safety reasons.

CREST: Combination of sasanlimab and alternative BCG Regimens to Evaluate outcomes with Subcutaneous anti-PD-1 Treatment

Phase 3 Design with two Cohorts. Cohort A consists of 3 study Arms (A, B and C) of BCG naive participants. Arms A and B consist of two study drugs, PF-06801591 plus BCG. Arm C consists of one study drug, BCG. Cohort B consists of B1 and B2, which test PF-06801591 and include participants who have BCG unresponsive CIS (B1) or BCG unresponsive papillary only disease (B2).

The study is designed to demonstrate that PF-06801591 plus Bacillus Calmette Guerin (BCG) (induction and maintenance periods) is superior to BCG alone (induction and maintenance periods) in prolonging event free survival (EFS) in participants with high-risk naïve non-muscle invasive bladder cancer (NMIBC) and to demonstrate that PF-06801591 plus BCG (induction period only) is superior to BCG alone (induction and maintenance periods) in prolonging EFS in participants with high-risk NMIBC. The study is also designed to estimate the CR rate of PF-06801591 alone in participants with BCG unresponsive CIS and to evaluate the EFS of PF-06801591 alone in participants with BCG unresponsive NMIBC.

On August 31, 2022, the Sponsor announced the discontinuation of enrollment to Part B, which enrolled participants with BCG unresponsive NMIBC. The decision to discontinue enrollment to Part B was not made for safety reasons.

A Study of Sasanlimab in People With Non-muscle Invasive Bladder Cancer

A Phase 3, Multinational, Randomized, Open-Label, Three Parallel-Arm Study of PF-06801591, an Anti-PD-1 Antibody, in Combination With Bacillus Calmette-Guerin (BCG Induction With or Without BCG Maintenance) Versus BCG (Induction and Maintenance) in Participants With High-Risk, BCG-Naïve Non-Muscle Invasive Bladder Cancer or PF-06801591 as a Single Agent in Participants With BCG-Unresponsive NMIBC

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Event free survival is defined as the time from randomization to date of EFS event.

Complete response (CR) rate defined as the proportion of participants in the analysis population with CR.

Event free survival is defined as the time from first dose to date of EFS event.

Overall survival is defined as the time from the date of randomization to the date of death due to any cause.

Disease specific survival (DSS) is defined as the time from randomization to death resulting from bladder cancer.

EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties).

Ctrough will be summarized in Cohort A Arms A and B only.

Immunogenicity will be evaluated for Cohort A Arms A and B only.

Duration of CR is defined as time from first CR to first recurrence or death due to any cause, whichever occurs first.

Time to recurrence defined as time from randomization to the date of first documentation of recurrence of low grade disease or death due to any cause, whichever occurs first.

Time to cystectomy is defined as time from randomization/registration to cystectomy in participants with NMIBC

PTAB is a 2-item PRO designed to assess, from the patient perspective, any pain associated with the treatment administration and the burden of the amount of time required to complete the treatment administration procedures (1 item each).

An adverse event (AE) is any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs comprised both SAEs and non-SAEs. Causality assessment is made by the investigator. Grading is per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0.

Percentage of participants with laboratory test abnormalities without regard to baseline abnormality. Grading is per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0.

EORTC-QLQ-NMIBC24 has 24 items which can be grouped into 6 subscales: urinary symptoms (7 items), malaise (2 items), future worries (4 items), bloating/flatulence (2 items), sexual functioning (2 items), and male sexual issues (2 items). The NMIBC24 also assesses intravesical treatment, female sexual issues, sexual intimacy, risk of contaminating a partner, and sexual enjoyment (1 item each).

Complete response (CR) rate defined as the proportion of participants in the analysis population with CR at 12 months.

Time from first dose to date of EFS event.

Time from the date of first dose to the date of death due to any cause.

Immunogenicity will be evaluated for participants with BCG unresponsive NMIBC, including those with CIS.

Cmax will be summarized in Cohort B2 only.

Pfizer

Substance Related Disorders

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Study Subjects randomized to the interventional arm will be assigned to BCG induction therapy once-weekly for 6 weeks and subsequent 1 year of maintenance (6+3x3) of which dwell-time during the first of the 6 induction instillations is 2 hours.

If side effects are registered before the second and all further instillations, Study Subject in the intervention arm will be reduced in dwell-time according to the grading of side effects as given by the study algorithm.

The Study Subjects will be treated according to guidelines with BCG instillation therapy once weekly for 6 weeks and subsequent 1 year of maintenance therapy (6+3x3) with 2 hours of dwelltime.

The same dose of the drug will be given in both arms but the dwell-time will be adjusted for the subjects in the intervention arm according to the grading of side effects given by the study algorithm.

Jørgen B. Jensen, Professor,DMSc

Lene Munk, MD

Knud Fabrin, MD

Gitte Lam, MD

Erik Hansen, MD

Ulla Nordström Joensen, MD, PhD Assoc. Professor

Lasse Bro, MD

Juan Luis Vásquez, MD

Sigurdur Gudjonsson

Viveka Ströck, MD

Tomas Thiel, MD

Tomas Jerlsström

Previous studies show that the majority NMIBC patients experience side effects to BCG and therefore terminate the instillations before completing all planned instillations. This will increase their risk of recurrence and potential cystectomy. The purpose of this study is to investigate if NMIBC patients who experience severe side effects to BCG instillations will experience fewer or less severe side effects if reducing dwell-time of BCG instillations.

The study will include patients from Denmark, Iceland, Norway and Sweden.

Approximately 8,000 patients are diagnosed with bladder cancer (BC) in the Nordic countries every year. The majority of BC patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). The majority of NMIBC are treated with Bacillus Calmette-Guérin vaccine (BCG) as adjuvant treatment but for carcinoma in situ it is the primary treatment. BCG is known to give a lot of side effects both local and systemic, the severity of these can lead to premature termination of the treatment.

The object of this PhD project is to investigate if reduced dwell time, the time the BCG is in the bladder, will decrease the severity of side effects due to BCG instillations.

This will be investigated in a Nordic setting and the project will be done as a two-armed randomized clinical trial.

By decreasing the severity of side effects, we hypothesize the number of patients completing all planned instillations will increase and thereby decrease the risk of the BC evolving into a more aggressive type.

multi-center, multi-national, two-armed, randomized, open-label, investigator-initiated clinical controlled - phase IV trial.

NORTH-REG Dwell-Time Study

Nordic Urothelial Cancer Research Group Study on Reduced BCG Dwell-Time in High Risk NMIBC

Number of Study Subjects completing all 6 induction instillations and subsequent maintenance installations for 12 months (6 + 3 x 3)

Recurrence rate within 24 months in Study Subjects with initial complete response

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Response to Intralesional IL-2 and/or BCG Treatment for Cutaneous Metastatic Melanoma	NCT03928275	Cutaneous Metas...	Interleukin-2 Combination the...	18 Years - 80 Years	Nova Scotia Health Authority
Intravesical BCG vs GEMDOCE in NMIBC	NCT05538663	Non-muscle-inva...	Gemcitabine Docetaxel Bacillus Calmet...	18 Years -	Eastern Cooperative Oncology Group
Immunological Response of Bladder Cancer Patients Under BCG	NCT04806178	Bladder Cancer Bacillus Calmet...	Bacillus Calmet... PLACEBO	18 Years -	University of Campinas, Brazil
The Response to Intralesional IL-2 and/or BCG Treatment for Cutaneous Metastatic Melanoma	NCT03928275	Cutaneous Metas...	Interleukin-2 Combination the...	18 Years - 80 Years	Nova Scotia Health Authority
A Study of Sasanlimab in People With Non-muscle Invasive Bladder Cancer	NCT04165317	Non-muscle Inva...	PF-06801591 Bacillus Calmet...	18 Years -	Pfizer
Intravesical BCG vs GEMDOCE in NMIBC	NCT05538663	Non-muscle-inva...	Gemcitabine Docetaxel Bacillus Calmet...	18 Years -	Eastern Cooperative Oncology Group
NORTH-REG Dwell-Time Study	NCT04701151	Side Effect of ...	Bacillus Calmet...	18 Years -	Aarhus University Hospital

Spots Global Cancer Trial Database for bacillus calmette guerin