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Advanced Solid TumorPhase 1/2NCT04742959

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

A Phase 1/2 study testing TT-00420 and Nab-Paclitaxel in people with Advanced Solid Tumor and Cholangiocarcinoma, run by TransThera Sciences (Nanjing), Inc. at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TT-00420 and Nab-Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
203 participants
Where
6 sitesUnited States
Study dates
14 Mar 2021to 20 Feb 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 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
Show all 14Show fewer
  • 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

Who cannot join

  • 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)
Show all 30Show fewer
  • ≥ 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Gabrail Cancer Center Research

    Canton, Ohio, 44718

  • The University of Chicago

    Chicago, Illinois, 60637

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • City of Hope

    Duarte, California, 91010

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Rutgers Cancer Institute

    New Brunswick, New Jersey, 08901

Other trials in United States

About this study

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

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.

Read the 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.).

Being tested
TT-00420, Nab-Paclitaxel
Medical subject headings
Cholangiocarcinoma, Triple Negative Breast Neoplasms, Urinary Bladder Neoplasms, Small Cell Lung Carcinoma, Prostatic Neoplasms, Thyroid Neoplasms, Sarcoma, Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TT-00420Drug

    TT-00420 tablet will be administered orally once daily per protocol defined schedule.

  • Nab-PaclitaxelCombination product

    Nab-Paclitaxel would be administered via infusion on Day 1,8, and 15 of 28-day cycle

Study groups in NCT04742959
Study groupRoleWhat they receive
Monotherapy CohortsExperimentalTT-00420 tablets will be administered once daily in 28-day cycles.
Receives: Drug: TT-00420
Dose Escalation Cohorts (Combination Therapy)ExperimentalTT-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).
Receives: Drug: TT-00420; Combination Product: Nab-Paclitaxel
PK Run-in CohortsExperimentalTT-00420 tablets will be administered once or twice daily in 28-day cycles according to assigned cohort.
Receives: Drug: TT-00420

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Up to 30 days from study discontinuation

  2. Dose limiting toxicity (DLT)

    Dose escalation cohorts are monitored and assessed using the NCI Common Toxicity Criteria for Adverse Events, version 5.0.

    Measured: Up to 28 days from the first dose

Secondary outcomes (11)

  1. 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.

    Measured: Through study completion, an average of 9 months.

  2. Disease Control Rate (DCR)

    Defined as CR + PR + stable disease (SD) based on RECIST version 1.1.

    Measured: Through study completion, an average of 9 months.

  3. Duration of Objective Response (DOR)

    Duration of response for CR or PR based on RECIST version 1.1.

    Measured: Through study completion, an average of 9 months.

  4. Progression Free Survival (PFS)

    Measured: 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)

    Measured: From first study drug administration until the date of death from any cause, assessed up to 24 months

  6. Area under the curve (AUC0-∞)

    Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.

    Measured: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)

  7. 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.

    Measured: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)

  8. Maximum observed concentration (Cmax)

    Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.

    Measured: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)

  9. Half-life (T1/2)

    Measured: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)

  10. Time to Maximum Concentration (Tmax)

    Measured: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)

  11. Volume of Distribution (Vd)

    Measured: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2021
  2. Study start14 Mar 2021
  3. Primary completion20 Feb 2024
  4. Study completion20 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
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)
Enrolment
203 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04742959
Sponsor's protocol ID
TT420X1103
Status last verified
Dec 2023
First submitted
2 Feb 2021
Last updated
26 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TT-00420 and Nab-Paclitaxel in people with Advanced Solid Tumor and Cholangiocarcinoma, run by TransThera Sciences (Nanjing), Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04742959.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2024.

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