## Protocol Section
### Identification Module
**NCT ID:** NCT06417190

**Brief Title:** Bladder Preservation for Patients With Muscle Invasive Bladder Cancer (MIBC) With Variant Histology

**Official Title:** IIT2023-13-BALLAS-VHTMT: Bladder Preservation for Patients With Muscle Invasive Bladder Cancer (MIBC) With Variant Histology

#### Organization Study ID Info
**ID:** IIT2023-13-BALLAS-VHTMT
#### Organization
**Class:** OTHER
**Full Name:** Cedars-Sinai Medical Center
### Status Module
#### Completion Date
**Date:** 2030-07

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-15

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2030-07

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-13
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Leslie Ballas

#### Responsible Party

**Investigator Affiliation:** Cedars-Sinai Medical Center

**Investigator Full Name:** Leslie Ballas

**Investigator Title:** Sponsor-Investigator

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This is a Phase II, single cohort study designed to evaluate outcomes in patients with muscle invasive bladder cancer (MIBC) with variant histology who receive neoadjuvant chemotherapy (NAC) with or without immunotherapy (IO) followed by trimodal therapy (TMT). Enrolled patients will undergo at least 3 cycles of NAC +/- IO (oncologist's choice) followed by a four- or six-week course of concurrent standard of care chemotherapy and radiation therapy. These patients will be compared with historical controls of patients with a diagnosis of pure urothelial carcinoma who have undergone TMT. This study has been designed to test the hypothesis that variant histology TMT can be delivered within 45 days of NAC +/- IO and is therefore a viable option in patients who are risk of systemic disease spread.

**Detailed Description:** Trimodal therapy (TMT) is accepted as an NCCN category 1 alternative to radical cystectomy (with neoadjuvant chemotherapy) in patients with cT2N0M0 muscle-invasive urothelial cell bladder cancer (MIBC). Not all patients with MIBC have pure urothelial cell carcinoma; urothelial carcinoma with variant histology (VH) described any morphologic variant of conventional urothelial carcinoma that is believed to be derived from urothelial carcinoma and is typically admixed with conventional urothelial carcinoma in the same tumor. Variant histologies described include squamous differentiation, glandular differentiation, micropapillary, sarcomatoid, small cell/neuroendocrine, plasmacytoid and nested variant. This is a rare tumor type and understudied. For patients with variant histologies there is limited data on the use of trimodal therapy. There are a couple single institution retrospective studies and data from the NCDB, but no prospective data.

### Conditions Module

**Conditions:**

- Muscle-Invasive Bladder Carcinoma

- Tumor

**Keywords:**

- Trimodal Therapy (TMT)

- Neoadjuvant Chemotherapy

- muscle-invasive urothelial cell bladder cancer (MIBC)

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Single-arm, open-label

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Neoadjuvant chemotherapy followed by trimodal therapy consisting of TURBT followed by concurrent chemotherapy with radiation therapy

**Intervention Names:**

- Drug: Trimodal therapy (TMT) within 45 days of neoadjuvant chemotherapy (NAC)

**Label:** Single Arm

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Single Arm

**Description:** Single-arm, open-label

**Name:** Trimodal therapy (TMT) within 45 days of neoadjuvant chemotherapy (NAC)

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** To estimate progression free (\<=T2) survival rates from TMT

**Measure:** Progression free (<=T2) survival rates

**Time Frame:** 3 year

**Description:** To estimate the metastasis-free survival of TMT

**Measure:** Metastasis-free survival

**Time Frame:** 3 year

**Description:** To estimate the rate of salvage cystectomy following TMT

**Measure:** Rate of salvage cystectomy

**Time Frame:** 3 year

**Description:** To investigate blood and urine correlatives of clinical outcomes (Signatera and Oncuria)

**Measure:** Blood and urine correlatives of clinical outcomes

**Time Frame:** 3 year

#### Primary Outcomes

**Description:** To evaluate the feasibility of initiating TMT within 45 days of completion of NAC - Feasibility will be defined as at least 17 study participants initiating TMT within 45 days of NAC

**Measure:** Feasibility of initiating TMT

**Time Frame:** 45 days

#### Secondary Outcomes

**Description:** To estimate 3-year bladder intact event free survival (BIEFS) in patients undergoing TMT for MIBC with VH-TMT

**Measure:** 3-year bladder intact event free survival (BIEFS)

**Time Frame:** 3 year

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Documented diagnosis of MIBC with variant histology, cT2-T4N0M0, confirmed by TURBT and CT C/A/P and/or PET.
* Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

Exclusion Criteria:

* Evidence of diffuse cis on pathology
* Presence of bilateral hydronephrosis (if hydronephrosis is present, can only be unilateral)
* Prior radiotherapy to the pelvis
* History of systemic therapy for MIBS
* Presence of concurrent cancer (remote history of cancer (\>5 years) allowed if the patient is without evidence of disease)

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** cancer.trial.info@cshs.org

**Name:** Clinical Trial Navigator

**Phone:** 3104232133

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Los Angeles

**Contacts:**

***Contact 1:***

- **Email:** cancer.trial.info@cshs.org

- **Name:** Clinical Trial Recruitment Navigator

- **Phone:** 310-423-2133

- **Role:** CONTACT

***Contact 2:***

- **Name:** Leslie Ballas, MD

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 3:***

- **Name:** Anirban Mitra, MD, PhD

- **Role:** SUB_INVESTIGATOR

***Contact 4:***

- **Name:** Michael Ahdoor, MD

- **Role:** SUB_INVESTIGATOR

***Contact 5:***

- **Name:** Charles Rosser, MD

- **Role:** SUB_INVESTIGATOR

**Country:** United States

**Facility:** Cedars Sinai Medical Center

**State:** California

**Zip:** 90048

#### Overall Officials

**Official 1:**

**Affiliation:** Cedars-Sinai Medical Center

**Name:** Leslie Ballas, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014571

- Term: Urologic Neoplasms

- ID: D000014565

- Term: Urogenital Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000001745

- Term: Urinary Bladder Diseases

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M5030

- Name: Urinary Bladder Neoplasms

- Relevance: HIGH

- As Found: Bladder Cancer

- ID: M17320

- Name: Urologic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M17315

- Name: Urogenital Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M5026

- Name: Urinary Bladder Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001749

- Term: Urinary Bladder Neoplasms

### Misc Info Module

- Version Holder: 2024-05-31
