Safety and Tolerability Study for T-1101 (Tosylate) to Treat Advanced Refractory Solid Tumors

November 17, 2022 updated by: Taivex Therapeutics Corporation

A Phase I Safety and Tolerability Study of T-1101 (Tosylate) as a Oral Powder for Constitution (OPC) in Patients With Advanced Refractory Solid Tumors

T-1101 (Tosylate) is a new small molecule chemical entity being developed as a potential anti-cancer therapeutic by Taivex Therapeutics Corp. T-1101 (Tosylate) is a potent anti-cancer agent in numerous human cancer cell lines. In addition, oral administration of T-1101 (Tosylate) showed tumor growth inhibition in different mouse xenograft models of human cancers. In this study, safety, tolerability and PK of T-1101 (Tosylate) will be evaluated and also the recommended dose and regimen(s) to initiate Phase 2 will be determined.

Study Overview

Status

Terminated

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Taichung City 404327, Taiwan
        • China Medical University Hospital
      • Tainan, Taiwan, 701
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 110
        • Taipei Medical University Hospital
      • Taipei, Taiwan, 115
        • National Taiwan University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Tumor eligibility:

    • Histologically confirmed advanced malignancies refractory to standard active treatment.
    • Solid tumors that have measurable or evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1). Target lesions that have been previously irradiated will not be considered measurable (lesion) unless increase in size is observed following completion of radiation therapy.
  2. Able, in the investigator's opinion, to have a life expectancy of more than 3 months.
  3. Female or male, 20 years of age or older.
  4. ECOG performance status 0 or 1.
  5. Resolution of all acute toxic effects of prior therapy or surgical procedures to no more than grade 1 (except alopecia).
  6. Adequate organ function as defined by the following criteria:

    • Serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN), or ALT ≤ 5 x ULN if liver tumor is present.
    • Total serum bilirubin ≤1.5 x ULN
    • WBC ≥ 4000/µL with an absolute neutrophil count (ANC) ≥1500/µL
    • Platelets ≥ 100,000/µL
    • Hemoglobin ≥ 9.0 g/dL
    • CCr ≥ 50 mL/min
  7. Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment.
  8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

  1. Major surgery (as defined by investigator) within 4 weeks of starting treatment.
  2. Extensive radiation therapy or systemic cytotoxic chemotherapy within 4 weeks before starting study treatment or target therapy within 2 weeks of starting study treatment.
  3. Current treatment on clinical trial or within 4 weeks of completion of clinical trial for another investigation drug.
  4. Documented or suspicious brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
  5. Any of the following occurs within 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack.
  6. Ongoing cardiac dysrhythmias of NCI CTCAE grade 2, or atrial fibrillation of any grade.
  7. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy).
  8. Current treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).
  9. Known human immunodeficiency virus infection.
  10. Pregnancy or breastfeeding. Female patients must be surgically sterile or be postmenopausal, or must agree to the use of highly effective contraception during the period of therapy. Highly effective method of birth control is defined as one that results in a low failure rate (i.e. less than 1 percent per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, intra-uterine devices (IUDs), sexual abstinence, or a vasectomized partner. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
  11. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, which would make the patient inappropriate for entry into this study.
  12. Patients with active infection should be excluded.
  13. Positive test for hepatitis B (HBsAg) or hepatitis C (anti-HCV antibody).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: T-1101 (Tosylate)
T-1101 (Tosylate) powder in bottle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of T-1101 (Tosylate) in Participants with Advanced Cancers Refractory to Standard Therapy
Time Frame: The first 21-day cycle

MTD is highest dose level in which 6 patients have been treated with at most 1 experiencing dose limiting toxicity (DLT).

When following toxicity events occur within the first 21-day cycle, these toxicity will be defined as DLT.

  1. Hematological toxicities : prolonged grade 4 neutropenia for >7 days, grade 3 febrile neutropenia (an ANC < 1000/mm3 with a single temperature of > 38.3°C or a sustained temperature of > 38°C for more than 1 hour), grade 4 febrile neutropenia (febrile neutropenia with life-threatening consequences; urgent intervention indicated), grade 3 neutropenia with grade 3 infection and grade 3 thrombocytopenia with bleeding or grade 4 lasting 7 days.
  2. Non-hematological toxicities: grade 3 or 4 toxicities, Nausea and vomiting or diarrhea must persist at grade 3 or 4 despite maximal medical therapy.

The above toxicities will be graded according to the NCI CTCAE v4.03.

The first 21-day cycle

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Tumor Response of T-1101 (Tosylate) in Participants with Advanced Cancers
Time Frame: Up to 2 years
Categorization of response based on RECIST 1.1.
Up to 2 years
Pharmacokinetics: Peak maximum plasma concentration (Cmax) and minimum plasma concentration (Cmin) of T-1101 (Tosylate) and its metabolites
Time Frame: Selected time points during first 21-day cycle
Selected time points during first 21-day cycle
Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) to the time of the last measurable concentration and to infinity of T-1101 (Tosylate) and its metabolites
Time Frame: Selected time points during first 21-day cycle
Area under the plasma concentration versus time curve to the time of the last measurable concentration (AUC0-last) of T-1101 (Tosylate) and its metabolites will be estimated using non-compartmental analysis. If data permit, area under the plasma concentration versus time curve to infinity (AUC0-∞) will be also estimated.
Selected time points during first 21-day cycle
Pharmacokinetics: Time to maximum plasma concentration (Tmax) and terminal half-life (T½) of T-1101 (Tosylate) and its metabolites
Time Frame: Selected time points during first 21-day cycle
Time to maximum plasma concentration (Tmax) of T-1101 (Tosylate) and its metabolites will be estimated using non-compartmental analysis. If data permit, terminal elimination half-life (T½ ) will be also estimated.
Selected time points during first 21-day cycle
Pharmacokinetics: Oral plasma clearance (CL/F) of T-1101 (Tosylate) and its metabolites
Time Frame: Selected time points during first 21-day cycle
Selected time points during first 21-day cycle
Pharmacokinetics: Apparent volume of distribution (Vd/F) of T-1101 (Tosylate) and its metabolites
Time Frame: Selected time points during first 21-day cycle
Selected time points during first 21-day cycle

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 14, 2017

Primary Completion (Actual)

October 1, 2019

Study Completion (Actual)

October 23, 2019

Study Registration Dates

First Submitted

May 8, 2017

First Submitted That Met QC Criteria

June 19, 2017

First Posted (Actual)

June 22, 2017

Study Record Updates

Last Update Posted (Actual)

November 18, 2022

Last Update Submitted That Met QC Criteria

November 17, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TAI-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Advanced Refractory Solid Tumors

Clinical Trials on T-1101 (Tosylate)

3
Subscribe