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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04742959
Recruitment Status : Recruiting
First Posted : February 8, 2021
Last Update Posted : October 26, 2021
Sponsor:
Information provided by (Responsible Party):
TransThera Sciences (Nanjing), Inc.

Tracking Information
First Submitted Date  ICMJE February 2, 2021
First Posted Date  ICMJE February 8, 2021
Last Update Posted Date October 26, 2021
Actual Study Start Date  ICMJE July 14, 2021
Estimated Primary Completion Date April 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2021)
  • Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment [ Time Frame: Up to 30 days from study discontinuation ]
    As assessed per NCI Common Toxicity Criteria for Adverse Events, version 5.0
  • Dose limiting toxicity (DLT) [ Time Frame: Up to 28 days from the first dose ]
    Dose escalation cohorts are monitored and assessed using the NCI Common Toxicity Criteria for Adverse Events, version 5.0.
Original Primary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
  • Area under the curve (AUC0-∞) of TT-00420 tablet administered q.d or b.i.d [ Time Frame: From pre-dose up to 240 hours post-dose at the end of each crossover or dose escalation period (28 days) ]
    Blood sample will be collected at designated time points for pharmacokinetic analysis of TT-00420 tablet
  • Area under the curve (AUC0-t) of TT-00420 tablet administered q.d or b.i.d [ Time Frame: From pre-dose up to 240 hours post-dose at the end of each crossover or dose escalation period (28 days) ]
    Blood sample will be collected at designated time points for pharmacokinetic analysis of TT-00420 tablet
  • Maximum observed concentration (Cmax) of TT-00420 tablet administered q.d or b.i.d [ Time Frame: From pre-dose up to 240 hours post-dose at the end of each crossover or dose escalation period (28 days) ]
    Blood sample will be collected at designated time points for pharmacokinetic analysis of TT-00420 tablet
  • Dose limiting toxicity (DLT) [ Time Frame: Up to 28 days from the first dose ]
    Dose escalation cohorts are monitored and assessed using the NCI Common Toxicity Criteria for Adverse Events, version 5.0.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2021)
  • Objective Response Rate (ORR) [ Time Frame: Through study completion, an average of 9 months. ]
    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) [ Time Frame: Through study completion, an average of 9 months. ]
    Defined as CR + PR + stable disease (SD) based on RECIST version 1.1.
  • Duration of Objective Response (DOR) [ Time Frame: Through study completion, an average of 9 months. ]
    Duration of response for CR or PR based on RECIST version 1.1.
  • 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 ]
  • Overall Survival (OS) [ Time Frame: From first study drug administration until the date of death from any cause, assessed up to 24 months ]
  • Area under the curve (AUC0-∞) [ Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days) ]
    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) [ Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days) ]
    Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
  • Maximum observed concentration (Cmax) [ Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days) ]
    Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
  • Half-life (T1/2) [ Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days) ]
  • Time to Maximum Concentration (Tmax) [ Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days) ]
  • Volume of Distribution (Vd) [ Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
  • Half-life (t1/2) of TT-00420 tablet administered q.d or b.i.d [ Time Frame: From pre-dose up to 240 hours post-dose at the end of each crossover or dose escalation period (28 days) ]
    Blood sample will be collected at designated time points for pharmacokinetic analysis of TT-00420 tablet
  • Time at maximum concentration (Tmax) of TT-00420 tablet administered q.d or b.i.d [ Time Frame: From pre-dose up to 240 hours post-dose at the end of each crossover or dose escalation period (28 days) ]
    Blood sample will be collected at designated time points for pharmacokinetic analysis of TT-00420 tablet
  • Objective Response Rate (ORR) [ Time Frame: Through study completion, an average of 9 months. ]
    Tumor response evaluated per RECIST V1.1
  • Disease Control Rate (DCR) [ Time Frame: Through study completion, an average of 9 months. ]
    Tumor response evaluated per RECIST V1.1
  • Duration of Objective Response (DOR) [ Time Frame: Through study completion, an average of 9 months. ]
    Tumor response evaluated per RECIST V1.1.
  • Progression Free Survival (PFS) [ Time Frame: Through study completion, an average of 9 months. ]
    Tumor response evaluated per RECIST V1.1.
  • Overall Survival (OS) [ Time Frame: Through study completion, an average of 9 months ]
  • Number of participants with adverse events (AEs) [ Time Frame: Up to 30 days from study discontinuation ]
    Assessed by CTCAE V5.0 or the most current version.
  • Incidence of abnormal clinical laboratory test [ Time Frame: Up to 30 days from study discontinuation ]
  • Incidence of abnormal physical examination [ Time Frame: Up to 30 days from study discontinuation ]
  • Incidence of abnormal vital signs [ Time Frame: Up to 30 days from study discontinuation ]
  • Incidence of abnormal 12-lead ECG [ Time Frame: Up to 30 days from study discontinuation ]
Current Other Pre-specified Outcome Measures
 (submitted: June 5, 2021)
Genetic Alteration Status [ Time Frame: Through study completion, an average of 9 months ]
Evaluation of biomarkers, including but not limited to, fibroblast growth factor receptor (FGFR) mutation status
Original Other Pre-specified Outcome Measures
 (submitted: February 2, 2021)
Exploratory biomarkers [ Time Frame: Through study completion, an average of 9 months ]
FGFR fusions (or other aberrations)
 
Descriptive Information
Brief Title  ICMJE Study of TT-00420 Tablet as Monotherapy and Combination Therapy in Patients With Advanced Solid Tumors
Official Title  ICMJE A Phase Ib/II, Multicenter, Open-Label Study of TT-00420 Tablet, as Monotherapy or in Combination Regimens, in Patients With Advanced Solid Tumors
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 two arms, Arm A is a Phase Ib/II study of TT-00420 tablet monotherapy, and Arm B is a Phase Ib/II study of TT-00420 tablet in combination with nab-paclitaxel (Abraxane®).

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Study will consist of two arms: Arm A (TT-00420 Tablet Monotherapy) and Arm B (TT-00420 tablet in combination with nab-paclitaxel (Abraxane®)).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: TT-00420
    TT-00420 tablet will be administered orally once daily per protocol defined schedule.
  • Combination Product: Nab-Paclitaxel
    Nab-Paclitaxel would be administered via infusion on Day 1,8, and 15 of 28-day cycle
Study Arms  ICMJE
  • Experimental: Monotherapy Cohorts
    TT-00420 tablets will be administered once daily in 28-day cycles.
    Intervention: Drug: TT-00420
  • Experimental: Dose Escalation Cohorts (Combination Therapy)
    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).
    Interventions:
    • Drug: TT-00420
    • Combination Product: Nab-Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 5, 2021)
105
Original Estimated Enrollment  ICMJE
 (submitted: February 2, 2021)
28
Estimated Study Completion Date  ICMJE December 1, 2022
Estimated Primary Completion Date April 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 24-hour 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Peng Peng, Ph.D. 86-25-86901107 peng_peng@transtherabio.com
Contact: Hui Wang 86-25-86901159 wang_hui@transtherabio.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04742959
Other Study ID Numbers  ICMJE TT420X1103
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party TransThera Sciences (Nanjing), Inc.
Study Sponsor  ICMJE TransThera Sciences (Nanjing), Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sarina A. Piha-Paul, MD M.D. Anderson Cancer Center
PRS Account TransThera Sciences (Nanjing), Inc.
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP