Trial Title:
A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With Select Solid Tumors
NCT ID:
NCT05683418
Condition:
Colorectal Cancer
Gastric Cancer
HER2-negative Breast Cancer
Non-small Cell Lung Cancer
Squamous Cell Carcinoma of Head and Neck
Urothelial Carcinoma
Cervical Cancer
Ovarian Cancer
Endometrial Cancer
Conditions: Official terms:
Carcinoma
Endometrial Neoplasms
Squamous Cell Carcinoma of Head and Neck
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
TOS-358 Single Agent Arm:
Part 1(multiple ascending doses, QD or BID): locally advanced, recurrent or metastatic
select solid tumors with PIK3CA mutation per local assessment; Part 2 (RP2D determined in
Part 1) Patients with locally advanced, recurrent or metastatic select solid tumors with
PIK3CA mutation per local assessment will be enrolled protocol defined groups
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
TOS-358
Description:
Covalent Phosphoinositide-3-Kinase (PI3K)-alpha Inhibitor
Arm group label:
TOS-358 Single Agent Arm
Summary:
The goal of this clinical trial is to evaluate the safety of TOS-358 in adults with
select solid tumors who meet study enrollment criteria. The main questions it aims to
answer are:
1. what is the maximum tolerated dose and recommended dose for phase 2?
2. how safe and tolerable is TOS-358 at different dose levels when taken orally once or
twice per day?
Detailed description:
This study will be conducted in two parts: a dose finding portion to determine the
maximum tolerated dose and recommended phase 2 dose (RP2D) of TOS-358 administered orally
on once a day (QD) and twice daily (BID) schedules, and a dose expansion portion to
evaluate safety and tolerability in tumor-specific cohorts administered TOS-358 at the
recommended phase 2 dose and schedule.
Adult subjects with histologically confirmed diagnosis of colorectal cancer, gastric
cancer, non-small cell lung cancer, human epidermal growth factor receptor 2 (HER2)
negative breast cancer, squamous cell carcinoma of the head and neck, urothelial cancer,
or select gynecologic cancers (ovarian cancer, cervical cancer, or endometrial cancer)
with known PIK3CA mutations or amplifications (as determined at a College of American
Pathologists/clinical laboratory improvement amendments [CAP/CLIA]-certified or
equivalently accredited diagnostic laboratory using a validated test), who meet all of
the eligibility criteria will be enrolled in the Phase 1 portion of the study.
In the dose finding portion of the study, TOS-358 will be evaluated as a single-agent at
multiple dose levels administered orally until disease progression, unacceptable
toxicity, or until meeting any other reason for discontinuation as specified in the
protocol.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria
- Locally advanced, recurrent, or metastatic, incurable (any number of previous lines
of therapy is allowed), histologically or cytologically confirmed: colorectal
cancer; gastric cancer; non-small cell lung cancer; HER2- breast cancer; squamous
cell carcinoma of the head and neck; urothelial cancer; or select gynecologic cancer
(ovarian cancer, cervical cancer, or endometrial cancer)
- Willing and able to provide written informed consent for this study
- Adults ≥ 18 years old at time of consent
- Known PIK3CA mutations or amplifications as determined at a CAP/CLIA-certified or
equivalently accredited diagnostic laboratory using a validated test
- Measurable disease by RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy ≥ 3 months, as determined by the investigator
- Adequate bone marrow, liver, and kidney function within 14 days prior to first dose
of investigational product
- Fasting plasma glucose < 126 mg/dL AND hemoglobin A1c (HbA1c) < 5.7%
- Available archived or fresh tumor tissue sample for detection of PIK3CA mutation by
central laboratory test
Key Exclusion Criteria
- Recent systemic anticancer treatment prior to start of treatment
- Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism
of action is to inhibit the PI3K-AKT-mTOR pathway, except for patients with breast
cancer
- Second malignancy (solid or hematologic) within the past 3 years except: Adequately
treated basal cell or squamous cell skin cancer; carcinoma in situ of the cervix, or
prostate cancer with Gleason score < 6 and undetectable prostate specific antigen
over 12 months ;ductal breast carcinoma in situ with full surgical resection (ie,
negative margins); treated medullary or papillary thyroid cancer; metaplastic breast
cancer
- History of diabetes of any type
- Body mass index (BMI) ≥ 30
- Cushing syndrome
- Congestive heart failure (New York Heart Association Class III to IV), symptomatic
ischemia, conduction abnormalities uncontrolled by conventional intervention, or
myocardial infarction within 6 months prior to the first dose of investigational
product
- Known active central nervous system (CNS) metastases.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Marwan Fakih, MD
Phone:
626-256-4673
Email:
mfakih@coh.org
Investigator:
Last name:
Marwan Fakih, MD
Email:
Principal Investigator
Facility:
Name:
University of Southern California, Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
Xiomara Menendez, RN
Email:
Xiomara.Menendez@med.usc.edu
Investigator:
Last name:
Anthony El-Khoueiry, MD
Email:
Principal Investigator
Facility:
Name:
Yale University, Yale Cancer Center
Address:
City:
New Haven
Zip:
06520
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ingid Palma
Phone:
203-833-1034
Email:
ingrid.palma@yale.edu
Investigator:
Last name:
Patricia LoRusso, DO, PhD
Email:
Principal Investigator
Facility:
Name:
Northwestern Memorial Hospital
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
312-695-1301
Email:
cancer@northwestern.edu
Investigator:
Last name:
Aparna Kalyan, MD
Email:
Principal Investigator
Facility:
Name:
University of Maryland Greenbaum Comprehensive Cancer Center
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kristen Judy
Email:
Kristen.Judy@umm.edu
Investigator:
Last name:
Ranee Mehra, MD
Email:
Principal Investigator
Facility:
Name:
Massachusetts General Hospital Cancer Center
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andreas Andreas, MD, PhD
Phone:
617-724-4000
Email:
avarkaris@mgh.harvard.edu
Investigator:
Last name:
Andreas Andreas, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Beth Israel Deaconess Medical Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Susan Gotthardt
Phone:
617-975-7452
Email:
sgotthar@bidmc.harvard.edu
Investigator:
Last name:
Gerburg Wulf, MD
Email:
Principal Investigator
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Emily McClure, RN
Phone:
857-215-0180
Email:
emily_mcclure@dfci.harvard.edu
Investigator:
Last name:
Antonio Giordano,, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Henry Ford Hospital
Address:
City:
Detroit
Zip:
48202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Huzaifa Hussain
Phone:
313-874-7524
Email:
hhussai2@hfhs.org
Investigator:
Last name:
Philip Philip, MD
Email:
Principal Investigator
Facility:
Name:
University of Cincinnati Medical Center
Address:
City:
Cincinnati
Zip:
45219
Country:
United States
Status:
Recruiting
Contact:
Last name:
Davendra Sohal, MD
Phone:
513-558-2361
Email:
sohalda@ucmail.uc.edu
Investigator:
Last name:
Davendra Sohal, MD
Email:
Principal Investigator
Facility:
Name:
University Hospitals Cleveland Medical Center
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Status:
Recruiting
Contact:
Last name:
David Bajor, MD
Email:
David.Bajor@Uhhospitals.org
Investigator:
Last name:
David Bajor, MD
Email:
Principal Investigator
Facility:
Name:
Stephenson Cancer Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christina Caldwell, LPN
Phone:
405-271-8001
Email:
Christina-Caldwell@ouhsc.edu
Investigator:
Last name:
Susanna Ulahannan, MD
Email:
Principal Investigator
Facility:
Name:
University of Pennsylvania
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Email:
PAhemoncResearch@uphs.upenn.edu
Investigator:
Last name:
Thomas Karasic, MD
Email:
Principal Investigator
Facility:
Name:
Vanderbilt-Ingram Cancer Center
Address:
City:
Nashville
Zip:
37232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jordan Berlin, MD
Phone:
800-811-8480
Email:
CTIP@VUMC.ORG
Investigator:
Last name:
Jordan Berlin, MD
Email:
Principal Investigator
Facility:
Name:
START- Mountain Region
Address:
City:
West Valley City
Zip:
84119
Country:
United States
Status:
Recruiting
Contact:
Last name:
Marie Asay
Phone:
801-907-4770
Email:
marie.asay@startthecure.com
Investigator:
Last name:
Justin Call, MD
Email:
Principal Investigator
Facility:
Name:
Virginia Cancer Specialists, PC
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Last name:
Carrie Friedman, RN, BSC, OCN
Phone:
703-636-1473
Email:
carrie.friedman@usoncology.com
Investigator:
Last name:
Alexander Spira, MD
Email:
Principal Investigator
Start date:
February 15, 2023
Completion date:
December 2025
Lead sponsor:
Agency:
Totus Medicines
Agency class:
Industry
Source:
Totus Medicines
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05683418
