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

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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.

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.

Condition or disease Intervention/treatment Phase
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 Drug: TT-00420 Combination Product: Nab-Paclitaxel Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 participants
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
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
Actual Study Start Date : July 14, 2021
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : December 1, 2022


Arm Intervention/treatment
Experimental: Monotherapy Cohorts
TT-00420 tablets will be administered once daily in 28-day cycles.
Drug: TT-00420
TT-00420 tablet will be administered orally once daily per protocol defined schedule.

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).
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




Primary Outcome Measures :
  1. 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

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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 ]
  5. Overall Survival (OS) [ Time Frame: From first study drug administration until the date of death from any cause, assessed up to 24 months ]
  6. 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.

  7. 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.

  8. 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.

  9. Half-life (T1/2) [ Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days) ]
  10. Time to Maximum Concentration (Tmax) [ Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days) ]
  11. Volume of Distribution (Vd) [ Time Frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days) ]

Other Outcome Measures:
  1. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04742959


Contacts
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Contact: Peng Peng, Ph.D. 86-25-86901107 peng_peng@transtherabio.com
Contact: Hui Wang 86-25-86901159 wang_hui@transtherabio.com

Locations
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United States, California
City of Hope Not yet recruiting
Duarte, California, United States, 91010
United States, New Jersey
Rutgers Cancer Institute Recruiting
New Brunswick, New Jersey, United States, 08901
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
TransThera Sciences (Nanjing), Inc.
Investigators
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Principal Investigator: Sarina A. Piha-Paul, MD M.D. Anderson Cancer Center
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Responsible Party: TransThera Sciences (Nanjing), Inc.
ClinicalTrials.gov Identifier: NCT04742959    
Other Study ID Numbers: TT420X1103
First Posted: February 8, 2021    Key Record Dates
Last Update Posted: October 26, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Small Cell Lung Carcinoma
Thyroid Neoplasms
Triple Negative Breast Neoplasms
Cholangiocarcinoma
Gallbladder Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms by Histologic Type
Digestive System Neoplasms
Digestive System Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Endocrine Gland Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Thyroid Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Biliary Tract Neoplasms
Biliary Tract Diseases
Gallbladder Diseases