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Study of TT-00420 Tablet as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors

Primary Purpose

Advanced Solid Tumor, Cholangiocarcinoma, HER2-negative Breast Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TT-00420
Nab-Paclitaxel
Sponsored by
TransThera Sciences (Nanjing), Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumor

Eligibility Criteria

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

Inclusion Criteria:

  1. ≥ 18 years of age
  2. Histopathological or cytologically documented locally advanced or metastatic solid tumors who have no available standard therapeutic treatment options
  3. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. Adequate organ function confirmed at screening and within 10 days of initiating treatment, as evidenced by:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
    • Hemoglobin (Hgb) ≥ 8 g/dl
    • Platelets (plt) ≥ 75 x 10^9/L
    • AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases are present
    • Total bilirubin ≤ 1.5 x ULN
    • Calculated creatinine clearance ≥ 50 mL/min (Cockcroft Gault formula)
  6. Negative pregnancy test within 72 hours before starting study treatment in all premenopausal women and women < 12 months after the onset of menopause
  7. Must agree to take sufficient contraceptive methods to avoid pregnancy during the study and until at least 6 months after ceasing study treatment
  8. Able to sign informed consent and comply with the protocol

Exclusion Criteria:

  1. Women who are pregnant or lactating
  2. Women of child-bearing potential (WOCBP) who do not use adequate birth control
  3. Patients with any hematologic malignancy, including leukemia (any form), lymphoma, and multiple myeloma
  4. Patients with a history of primary central nervous system tumors or carcinomatous meningitis.
  5. Patients with the following mood disorders as judged by the Investigator or a psychiatrist:

    • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia; a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
    • ≥ CTCAE grade 3 anxiety
  6. Impaired cardiac function or significant diseases, including but not limited to any of the following:

    • left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO)
    • Congenital long QT syndrome
    • QTcF ≥ 480 msec on screening ECG
    • Unstable angina pectoris ≤ 3 months prior to starting study drug
    • Acute myocardial infarction ≤ 3 months prior to starting study drug
  7. Patients with:

    • unresolved diarrhea ≥ CTCAE grade 2, or
    • impairment of gastrointestinal (GI) function, or
    • GI disease that may significantly alter the absorption of TT-00420
  8. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., uncontrolled hypertension, uncontrolled hypertriglyceridemia, or active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
  9. Patients who have received chemotherapy, targeted therapy, or immunotherapy ≤ 4 weeks (6 weeks for nitrosourea or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy
  10. Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  11. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  12. Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 4 weeks prior to starting study drug.
  13. Patients who are currently receiving treatment with therapeutic doses of warfarin sodium or any other coumarin-derivative anticoagulants
  14. Patients who have received systemic corticosteroids ≤ 2 weeks prior to starting study drug or who have not recovered from the side effects of such treatment.
  15. Patients who are currently receiving treatment with strong CYP3A inhibitors or inducers ≤ 2 weeks prior to starting study drug.
  16. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory; patients with well controlled HIV might be enrolled)
  17. Known history of active infection with Hepatitis B or Hepatitis C
  18. Has received a live-virus vaccination within 30 days of planned first dose
  19. Inability to swallow or tolerate oral medication
  20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in the trial.

Sites / Locations

  • City of HopeRecruiting
  • The University of ChicagoRecruiting
  • Rutgers Cancer InstituteRecruiting
  • Gabrail Cancer Center ResearchRecruiting
  • UT Southwestern Medical CenterRecruiting
  • MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Monotherapy Cohorts

Dose Escalation Cohorts (Combination Therapy)

PK Run-in Cohorts

Arm Description

TT-00420 tablets will be administered once daily in 28-day cycles.

TT-00420 tablets will be administered once daily in 28-day cycles. Nab-paclitaxel 100 mg/m^2 will be administered intravenously on Day 1, 8, and 15 of each 28-day cycle. Dose escalation will be guided by a 3+3 design in Phase Ib to determine the recommended phase 2 dose (RP2D).

TT-00420 tablets will be administered once or twice daily in 28-day cycles according to assigned cohort.

Outcomes

Primary Outcome Measures

Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
As assessed per NCI Common Toxicity Criteria for Adverse Events, version 5.0
Dose limiting toxicity (DLT)
Dose escalation cohorts are monitored and assessed using the NCI Common Toxicity Criteria for Adverse Events, version 5.0.

Secondary Outcome Measures

Objective Response Rate (ORR)
The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.
Disease Control Rate (DCR)
Defined as CR + PR + stable disease (SD) based on RECIST version 1.1.
Duration of Objective Response (DOR)
Duration of response for CR or PR based on RECIST version 1.1.
Progression Free Survival (PFS)
Overall Survival (OS)
Area under the curve (AUC0-∞)
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
Area under the curve (AUC0-t)
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
Maximum observed concentration (Cmax)
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
Half-life (T1/2)
Time to Maximum Concentration (Tmax)
Volume of Distribution (Vd)

Full Information

First Posted
February 2, 2021
Last Updated
July 18, 2022
Sponsor
TransThera Sciences (Nanjing), Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04742959
Brief Title
Study of TT-00420 Tablet as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors
Official Title
A Phase Ib/II, Multicenter, Open-Label Study of TT-00420 Tablet, as Monotherapy or in Combination Regimens, in Patients With Advanced Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 14, 2021 (Actual)
Primary Completion Date
October 1, 2022 (Anticipated)
Study Completion Date
December 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TransThera Sciences (Nanjing), Inc.

4. Oversight

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

5. Study Description

Brief Summary
This is a Phase Ib/II, multicenter, open-label study to evaluate the safety and preliminary efficacy of TT-00420 tablet, as monotherapy or in combination regimens, in patients with advanced solid tumors.
Detailed Description
Study consists of three arms, Arm A is a Phase Ib/II study of TT-00420 tablet monotherapy, Arm B is a Phase Ib/II study of TT-00420 tablet in combination with nab-paclitaxel (Abraxane®) and Arm C is a PK run-in study of TT-00420 tablet. Arm A: TT-00420 Tablet Monotherapy Phase Ib will enroll patients with preferred indications including metastatic cholangiocarcinoma, HER2-negative breast cancer including TNBC, bladder cancer, small cell lung cancer, prostate cancer, thyroid cancer, sarcoma, gastric cancer, gallbladder cancer and other advanced solid tumors to receive TT-00420 monotherapy. Based on preliminary efficacy results, Phase II will enroll additional patients in select indications to evaluate the efficacy of TT-00420 monotherapy. Arm B: TT-00420 tablet in combination with nab-paclitaxel (Abraxane®) Arm B will enroll patients with metastatic HER2-negative breast cancers, including triple-negative breast cancer (TNBC). Phase Ib will be a dose escalation study of TT-00420 in combination with nab-paclitaxel, guided by 3+3 design, to determine a Recommended Phase 2 Dose (RP2D). Phase II will enroll additional patients with metastatic HER2-negative breast cancers to further evaluate the efficacy of the combination regimen. Arm C: PK Run-in Study of TT-00420 Tablet Arm C will enroll patients with preferred indications including cholangiocarcinoma, TNBC/HER2- negative breast cancer, prostate cancer, sarcoma, hepatocellular carcinoma (HCC), bladder cancer, small cell lung cancer, thyroid cancer, gastric cancer, gallbladder cancer and other advanced solid tumors to receive TT-00420 monotherapy administered as once daily (q.d.) or twice daily (b.i.d.).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumor, Cholangiocarcinoma, HER2-negative Breast Cancer, Triple Negative Breast Cancer, Bladder Cancer, Small-cell Lung Cancer, Prostate Cancer, Thyroid Cancer, Sarcoma, Gastric Cancer, Gallbladder Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Study will consist of three arms: Arm A (TT-00420 Tablet Monotherapy), Arm B (TT-00420 tablet in combination with nab-paclitaxel (Abraxane®)) and Arm C (PK Run-in Study of TT-00420 Tablet).
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
225 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Monotherapy Cohorts
Arm Type
Experimental
Arm Description
TT-00420 tablets will be administered once daily in 28-day cycles.
Arm Title
Dose Escalation Cohorts (Combination Therapy)
Arm Type
Experimental
Arm Description
TT-00420 tablets will be administered once daily in 28-day cycles. Nab-paclitaxel 100 mg/m^2 will be administered intravenously on Day 1, 8, and 15 of each 28-day cycle. Dose escalation will be guided by a 3+3 design in Phase Ib to determine the recommended phase 2 dose (RP2D).
Arm Title
PK Run-in Cohorts
Arm Type
Experimental
Arm Description
TT-00420 tablets will be administered once or twice daily in 28-day cycles according to assigned cohort.
Intervention Type
Drug
Intervention Name(s)
TT-00420
Intervention Description
TT-00420 tablet will be administered orally once daily per protocol defined schedule.
Intervention Type
Combination Product
Intervention Name(s)
Nab-Paclitaxel
Intervention Description
Nab-Paclitaxel would be administered via infusion on Day 1,8, and 15 of 28-day cycle
Primary Outcome Measure Information:
Title
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Description
As assessed per NCI Common Toxicity Criteria for Adverse Events, version 5.0
Time Frame
Up to 30 days from study discontinuation
Title
Dose limiting toxicity (DLT)
Description
Dose escalation cohorts are monitored and assessed using the NCI Common Toxicity Criteria for Adverse Events, version 5.0.
Time Frame
Up to 28 days from the first dose
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.
Time Frame
Through study completion, an average of 9 months.
Title
Disease Control Rate (DCR)
Description
Defined as CR + PR + stable disease (SD) based on RECIST version 1.1.
Time Frame
Through study completion, an average of 9 months.
Title
Duration of Objective Response (DOR)
Description
Duration of response for CR or PR based on RECIST version 1.1.
Time Frame
Through study completion, an average of 9 months.
Title
Progression Free Survival (PFS)
Time Frame
From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Title
Overall Survival (OS)
Time Frame
From first study drug administration until the date of death from any cause, assessed up to 24 months
Title
Area under the curve (AUC0-∞)
Description
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
Time Frame
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Title
Area under the curve (AUC0-t)
Description
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
Time Frame
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Title
Maximum observed concentration (Cmax)
Description
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
Time Frame
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Title
Half-life (T1/2)
Time Frame
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Title
Time to Maximum Concentration (Tmax)
Time Frame
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Title
Volume of Distribution (Vd)
Time Frame
From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Other Pre-specified Outcome Measures:
Title
Genetic Alteration Status
Description
Evaluation of biomarkers, including but not limited to, fibroblast growth factor receptor (FGFR) mutation status
Time Frame
Through study completion, an average of 9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥ 18 years of age Histopathological or cytologically documented locally advanced or metastatic solid tumors who have no available standard therapeutic treatment options At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ function confirmed at screening and within 10 days of initiating treatment, as evidenced by: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L Hemoglobin (Hgb) ≥ 8 g/dl Platelets (plt) ≥ 75 x 10^9/L AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases are present Total bilirubin ≤ 1.5 x ULN Calculated creatinine clearance ≥ 50 mL/min (Cockcroft Gault formula) Negative pregnancy test within 72 hours before starting study treatment in all premenopausal women and women < 12 months after the onset of menopause Must agree to take sufficient contraceptive methods to avoid pregnancy during the study and until at least 6 months after ceasing study treatment Able to sign informed consent and comply with the protocol Exclusion Criteria: Women who are pregnant or lactating Women of child-bearing potential (WOCBP) who do not use adequate birth control Patients with any hematologic malignancy, including leukemia (any form), lymphoma, and multiple myeloma Patients with a history of primary central nervous system tumors or carcinomatous meningitis. Patients with the following mood disorders as judged by the Investigator or a psychiatrist: Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia; a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) ≥ CTCAE grade 3 anxiety Impaired cardiac function or significant diseases, including but not limited to any of the following: left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO) Congenital long QT syndrome QTcF ≥ 480 msec on screening ECG Unstable angina pectoris ≤ 3 months prior to starting study drug Acute myocardial infarction ≤ 3 months prior to starting study drug Patients with: unresolved diarrhea ≥ CTCAE grade 2, or impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of TT-00420 Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., uncontrolled hypertension, uncontrolled hypertriglyceridemia, or active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol Patients who have received chemotherapy, targeted therapy, or immunotherapy ≤ 4 weeks (6 weeks for nitrosourea or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 4 weeks prior to starting study drug. Patients who are currently receiving treatment with therapeutic doses of warfarin sodium or any other coumarin-derivative anticoagulants Patients who have received systemic corticosteroids ≤ 2 weeks prior to starting study drug or who have not recovered from the side effects of such treatment. Patients who are currently receiving treatment with strong CYP3A inhibitors or inducers ≤ 2 weeks prior to starting study drug. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory; patients with well controlled HIV might be enrolled) Known history of active infection with Hepatitis B or Hepatitis C Has received a live-virus vaccination within 30 days of planned first dose Inability to swallow or tolerate oral medication Has a history or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in the trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peng Peng, Ph.D.
Phone
86-25-86901107
Email
peng_peng@transtherabio.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hui Wang
Phone
86-25-86901159
Email
wang_hui@transtherabio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sarina A. Piha-Paul, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
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
Lindsay Kilpatrick
Phone
626-256-4673
Email
lkilpatrick@coh.org
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aurelie Desgardin
Phone
773-834-7188
Email
adesgard@medicine.bsd.uchicago.edu
Facility Name
Rutgers Cancer Institute
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Demmie Aguilar
Phone
732-235-8914
Email
da572@cinj.rutgers.edu
Facility Name
Gabrail Cancer Center Research
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda Rich
Phone
330-492-3345
Email
arich@gabrailcancercenter.com
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qunfang Wan
Phone
713-745-6243
Email
QWan1@mdanderson.org

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of TT-00420 Tablet as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors

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