Sapanisertib in Treating Patients With Locally Advanced or Metastatic Bladder Cancer With TSC1 and/or TSC2 Mutations

NCT03047213 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 5 other identifiers: NCI-2015-00121150501595820000212689767UM1CA186689
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 20

Brief Summary

This pilot phase II trial studies how well sapanisertib works in treating patients with bladder cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic) with tuberous sclerosis (TSC)1 and/or TSC2 mutations (changes in deoxyribonucleic acid \[DNA\]). Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Metastatic Transitional Cell Carcinoma; Metastatic Urothelial Carcinoma; Stage IV Bladder Urothelial Carcinoma AJCC v7; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Locally Advanced Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (TSC1 Patients)

  Overall Response Rate is the proportion of the patients with either complete response (CR) or partial response (PR) by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) version 1.1. Complete Response (CR) is defined as disappearance of all target lesions and partial response (PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Overall Response Rate is the proportion of the patients with either complete response (CR) or partial response (PR) by Response Evaluation Criteria. In Solid Tumors Criteria (RECIST) version 1.1. Complete Response (CR) is defined as disappearance of all target lesions and partial response (PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Up to 4 weeks after last dose of study treatment (approximately 19 weeks)

Secondary Outcomes (3)

• Incidence of Toxicity (TSC1 Patients)

  Up to 4 weeks after last dose of study treatment (approximately 19 weeks)

• Progression-free Survival (PFS) (TSC1 Patients)

  Time from start of treatment to date of progression or death- (approximately 19 weeks)

• Overall Survival (OS) (TSC1 Patients)

  Time from start of treatment to time of death from any cause, up to approximately 9 months

Other Outcomes (4)

• Overall Response Rate (TSC2 Patients)

  Up to 4 weeks after last dose of study treatment (approximately 19 weeks)

• Incidence of Toxicity (TSC2 Patients)

  Up to 4 weeks after last dose of study treatment

• Progression-free Survival (TSC2 Patients)

  Time from start of treatment to date of progression or death, whichever occurs first, assessed up to 1 year

Study Arms (1)

Treatment (sapanisertib)

EXPERIMENTAL

Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Sapanisertib

Interventions

Sapanisertib DRUG

Given PO

Also known as: INK-128, INK128, MLN-0128, MLN0128, TAK-228

Treatment (sapanisertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Must have a histologically confirmed transitional cell carcinoma (TCC, also known as urothelial carcinoma), locally advanced or metastatic
• Patient must have TCCs tumors harboring a TSC1 or TSC2 mutation identified by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
• Unless the pre-screening was performed at Yale Clinical Molecular Pathology Lab (YCMPL), patients must have TCC tumor tissue available for submission in a form of at least 10 unstained slides or formalin-fixed paraffin-embedded (FFPE) block (FFPE block highly recommended and preferred) along with a buccal swab; if the number of slides is less than 10, a biopsy should be considered; if a biopsy is deemed unsafe, the case may be discussed with the study principal investigator (PI) and approval must be given for eligibility
• Patient must have developed disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine/cisplatin \[GC\], methotrexate-vinblastine-doxorubicin-cisplatin \[MVAC\], carboplatin, gemcitabine \[CarboGem\]) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence, or must be unfit or ineligible for cisplatin-based chemotherapy; there is no restriction on the number of prior lines of chemotherapeutics agents received
• Patients who progressed within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant regimen are considered second-line patients; therefore, these patients may be also eligible
• Patients who are unfit or ineligible for cisplatin-based chemotherapy as defined by any one of the following criteria are eligible for this trial:
• Eastern Cooperative Oncology Group (ECOG) performance score of 2
• Creatinine clearance \< 60 mL/min
• A hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies
• Grade \>= 2 peripheral neuropathy
• ECOG performance status =\< 2 (Karnofsky \>= 60 %)
• Life expectancy of greater than 12 weeks
• Hemoglobin \>= 9 g/dL
• Fasting serum glucose =\< 130 mg/dL

You may not qualify if:

• Patients who have had chemotherapy, immunotherapy, or investigational therapy, within 4 weeks (6 weeks for nitrosoureas or mitomycin C), or palliative radiotherapy within 2 weeks prior to the first dose of the study drug
• Patients who have not recovered from adverse events due to prior anti-cancer therapy to grade 1 or baseline; patients with stable, controlled grade 2 adverse events (AEs) such as peripheral neuropathy, hypothyroidism, hypertension, adrenal insufficiency or alopecia are allowed after discussing with the PI
• Patients with known symptomatic, untreated central nervous system (including brain, spinal cord); patients who have a history of brain/central nervous system (CNS) metastasis are eligible for the study provided that all the following criteria are met:
• Brain/CNS metastases which have been treated
• No evidence of disease progression for \>= 3 months before the first dose of study drug
• No hemorrhage after treatment
• Off-treatment with dexamethasone for 4 weeks before administration of the first dose of TAK-228
• No ongoing requirement for dexamethasone or anti-epileptic drugs
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN0128 (TAK-228)
• Subjects who are on systemic corticosteroids (intravenous (IV) or oral steroids, excluding inhaled, topical or ophthalmic corticosteroids), or anti-epileptic drugs for treated brain metastasis
• Subjects taking strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4, CYP2C19 or CYP2C9 within 1 week preceding the first dose of MLN0128 (TAK-228); if a subject requires treatment with strong inhibitors and/or inducers of CYP3A4, CYP2C19 and/or CYP2C9, alternative treatment must be considered; if no alternative is available, one such medication may be allowed after discussing with the study principle investigator
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding rate controlled atrial fibrillation/flutter), or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and breastfeeding women are excluded from this study because fertility and developmental studies with MLN0128 (TAK-228) have not been conducted and there is a potential risk for adverse events including teratogenicity and risk of abortion; breastfeeding should be discontinued if the mother is treated with MLN0128 (TAK-228)
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with MLN0128 (TAK-228); however, HIV patients treated with regimens that have low CYP450 inhibition may be allowed as long as the patient's general health and CD4 counts are within acceptable levels
• Patients with baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval \> 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (20)

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Keck Medical Center of USC Pasadena

Pasadena, California, 91105, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Nebraska Medicine-Bellevue

Bellevue, Nebraska, 68123, United States

Location

Nebraska Medicine-Village Pointe

Omaha, Nebraska, 68118, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, 37204, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

sapanisertib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Joseph Kim, MD, Associate Professor of Internal Medicine
• Organization: Yale School of Medicine: Medical Oncology

joseph.w.kim@yale.edu

(203) 200-4822

Study Officials

• Joseph W Kim

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2017
• First Posted: February 8, 2017
• Study Start: August 24, 2017
• Primary Completion: October 6, 2020
• Study Completion (Estimated): November 12, 2026
• Last Updated: April 13, 2026
• Results First Posted: February 11, 2025

Record last verified: 2025-11

Locations

US (20)