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A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With Select Solid Tumors

Primary Purpose

Colorectal Cancer, Gastric Cancer, HER2-negative Breast Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TOS-358
Sponsored by
Totus Medicines
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • City of HopeRecruiting
  • University of Southern California, Norris Comprehensive Cancer CenterRecruiting
  • University of Cincinnati Medical CenterRecruiting
  • University Hospitals Cleveland Medical CenterRecruiting
  • Stephenson Cancer CenterRecruiting
  • START- Mountain RegionRecruiting
  • Virginia Cancer Specialists, PCRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TOS-358 Single Agent Arm

Arm Description

Multiple doses of TOS-358 for oral administration.

Outcomes

Primary Outcome Measures

Determine the rate of dose-limiting toxicities (DLTs)
Incidence and severity of adverse events (AEs) and specific laboratory abnormalities graded according to NCI CTCAE v5

Secondary Outcome Measures

Full Information

First Posted
November 12, 2022
Last Updated
October 6, 2023
Sponsor
Totus Medicines
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1. Study Identification

Unique Protocol Identification Number
NCT05683418
Brief Title
A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With Select Solid Tumors
Official Title
A Study to Evaluate the Safety and Tolerability of the Covalent Phosphoinositide-3-Kinase (PI3K)-Alpha Inhibitor, TOS-358, in Adult Subjects With Select Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 15, 2023 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Totus Medicines

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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: what is the maximum tolerated dose and recommended dose for phase 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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
Masking
None (Open Label)
Allocation
N/A
Enrollment
241 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TOS-358 Single Agent Arm
Arm Type
Experimental
Arm Description
Multiple doses of TOS-358 for oral administration.
Intervention Type
Drug
Intervention Name(s)
TOS-358
Intervention Description
Covalent Phosphoinositide-3-Kinase (PI3K)-alpha Inhibitor
Primary Outcome Measure Information:
Title
Determine the rate of dose-limiting toxicities (DLTs)
Time Frame
First 21 days of treatment
Title
Incidence and severity of adverse events (AEs) and specific laboratory abnormalities graded according to NCI CTCAE v5
Time Frame
Start of treatment to 30 days after last dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials
Phone
Please e-mail
Email
clinicaltrials@totusmedicines.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ovid Trifan, MD, PhD
Organizational Affiliation
Totus Medicines
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marwan Fakih, MD
Phone
626-256-4673
Email
mfakih@coh.org
Facility Name
University of Southern California, Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiomara Menendez, RN
Email
Xiomara.Menendez@med.usc.edu
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Davendra Sohal, MD
Phone
513-558-2361
Email
sohalda@ucmail.uc.edu
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Bajor, MD
Email
David.Bajor@Uhhospitals.org
Facility Name
Stephenson Cancer Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina Caldwell, LPN
Phone
405-271-8001
Email
Christina-Caldwell@ouhsc.edu
Facility Name
START- Mountain Region
City
West Valley City
State/Province
Utah
ZIP/Postal Code
84119
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie Asay
Phone
801-907-4770
Email
marie.asay@startthecure.com
Facility Name
Virginia Cancer Specialists, PC
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carrie Friedman, RN, BSC, OCN
Phone
703-636-1473
Email
carrie.friedman@usoncology.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With Select Solid Tumors

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