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A Trial of HTI-1090 in Subjects With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03208959
Recruitment Status : Completed
First Posted : July 6, 2017
Last Update Posted : September 30, 2019
Sponsor:
Information provided by (Responsible Party):
Atridia Pty Ltd.

Brief Summary:
IDO1 is expressed in a wide variety of human tumors (eg. bladder, breast, colon, DLBCL, HNSCC, lung, ovarian, uterine, renal…), and contributes to tumoral resistance. HTI-1090 (also referred as SHR9146 in nonclinical study reports) is an orally bioavailable, highly potent, novel small-molecule IDO1/TDO dual inhibitor, with favorable preclinical oral bioavailability and safety profiles.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: HTI-1090 Phase 1

Detailed Description:
This is an open-label, dose escalation, phase I, study of HTI-1090 (also known as SHR9146), a small molecule that inhibits both indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) - two enzymes that catalyze the oxidation of L-tryptophan (Trp) into kynurenine (Kyn), thereby interrupting the immune escape and the attainment of immunologic tolerance. Dose escalation will use a modified "3+3" design and continue until a MTD or RP2D is identified. This study will also characterize the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HTI-1090 in subjects with advanced solid tumors.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Multicenter, Non-Randomized, Dose-Escalation Study to Evaluate the Safety and Tolerability of HTI-1090 in Patients With Advanced Solid Tumors
Actual Study Start Date : August 30, 2017
Actual Primary Completion Date : November 1, 2018
Actual Study Completion Date : January 23, 2019

Arm Intervention/treatment
Experimental: Dose level 1
HTI-1090 tablets will be orally administered on an empty stomach,twice daily, BID i.e., dosing will be 12 hours apart and at approximately the same times each day
Drug: HTI-1090
IDO/TDO inhibitor
Other Name: SHR9146

Experimental: Dose level 2
100% Increment from dose level 1
Drug: HTI-1090
IDO/TDO inhibitor
Other Name: SHR9146

Experimental: Dose level 3
100% Increment from dose level 2
Drug: HTI-1090
IDO/TDO inhibitor
Other Name: SHR9146

Experimental: Dose level 4
100% Increment from dose level 3
Drug: HTI-1090
IDO/TDO inhibitor
Other Name: SHR9146

Experimental: Dose level 5
50% Increment from dose level 4
Drug: HTI-1090
IDO/TDO inhibitor
Other Name: SHR9146




Primary Outcome Measures :
  1. Adverse events [ Time Frame: Cycle 1 (each cycle is 21 days) ]
    Incidence of AEs

  2. Laboratory results [ Time Frame: Cycle 1 (each cycle is 21 days) ]
    Incidence of laboratory abnormalities

  3. Vital signs [ Time Frame: Cycle 1 (each cycle is 21 days) ]
    Incidence of vital sign abnormalities

  4. Electrocardiogram [ Time Frame: Cycle 1 (each cycle is 21 days) ]
    Incidence of ECG abnormalities



Information from the National Library of Medicine

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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

To be eligible to participate in this study, each subject must meet all of the following criteria:

  1. Provision of signed fully informed consent prior to any study specific procedures
  2. Male or female aged 18 years or older
  3. Diagnosed (histologically or cytologically) with solid tumors and documented as advanced or metastatic disease for which there is no known effective anti-tumor treatment (refractory to or relapsed from standard therapies)
  4. Subjects may have received one prior IDO, or TDO, or IDO/TDO dual inhibitor therapy; PD-1 or PD-L1 inhibitor; or other therapy that targets T cell co-stimulation or co-inhibition more than 4 weeks prior to the first dose of HTI-1090 (Cycle 1, Day 1)
  5. An ECOG Performance Status (PS) of 0 or 1
  6. Have a life expectancy ≥ 12 weeks from proposed first dose date
  7. Patients must have had no recent major surgery, radiotherapy or chemotherapy over the past 28 days and be fully recover from toxicity before dosing
  8. Adequate laboratory parameters during the Screening Period as evidenced by:

    • Absolute neutrophil count ≥ 1.5×109/L (1,500/mm3)
    • Platelets ≥ 100×109/L (100,000/mm3)
    • Hemoglobin (Hgb) ≥ 9.0 g/dL (90 g/L)
    • Subjects may be transfused with red blood cells to improve Hgb levels.
    • Total bilirubin ≤ 1.5×ULN (≤ 2×ULN for subjects with liver metastases)
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; for subjects with liver metastases, ALT and AST ≤ 5×ULN
    • Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min (measured or calculated by Cockcroft-Gault method)
    • Clinically relevant and treatment resistant abnormalities in potassium, sodium, calcium (corrected for plasma albumin) or magnesium
  9. Evidence of post-menopausal status, permanent or surgically sterile, or negative serum pregnancy test for female patients of child-bearing potential. Women will be considered post-menopausal if they are over 50 years old and have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments. Permanent sterilization includes hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal occlusion. Tubal occlusion is considered a highly effective method of birth control but does not absolutely exclude the possibility of pregnancy. (The term occlusion refers to both occluding and ligating techniques that do not physically remove the oviducts). Women who have undergone tubal occlusion should be managed as if they are of child-bearing potential (e.g., undergo pregnancy testing as required by the study). Females of reproductive potential are required to use reliable contraception
  10. Patients must have ability to take and retain oral medication and have no malabsorption problems
  11. Willing and able to return to treatment center for follow up, as outlined as protocol

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): NCT03208959


Locations
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Australia, New South Wales
Icon Cancer Care Centre
South Brisbane, New South Wales, Australia, 4101
Sponsors and Collaborators
Atridia Pty Ltd.

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Responsible Party: Atridia Pty Ltd.
ClinicalTrials.gov Identifier: NCT03208959     History of Changes
Other Study ID Numbers: HTI-1090-101
First Posted: July 6, 2017    Key Record Dates
Last Update Posted: September 30, 2019
Last Verified: September 2019
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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Neoplasms