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Advanced Solid TumorsPhase 1/2NCT06239155

A Phase I/II Study of AST-3424 in Subjects With Advanced Solid Tumors

A Phase 1/2 study testing AST-3424 in people with Advanced Solid Tumors and Hepatocellular Carcinoma, run by Ascentawits Pharmaceuticals, Ltd at 7 sites in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

An open-label, Phase I/II study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of AST-3424 administered as a single agent Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AST-3424
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
7 sitesChina
Study dates
3 Sep 2019to 30 Nov 2025
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • phase I: dose escalation phase
  • Male or female, 18-70 years old.
  • Histologically and/or cytologically confirmed malignant solid tumors (including but not limited to hepatocellular carcinoma, intrahepatic cholangiocarcinoma, gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, renal cell carcinoma, non-small cell lung cancer, and castration-resistant prostate cancer) that are metastatic or unresectable and have failed standard treatment or no standard treatment, pr not suitable for standard treatment at this stage.
  • Once MTD is confirmed, participant in the Extended Dose group (MTD group) need to have at least one measurable lesion that meets the RECIST 1.1 criteria. Previously irradiated lesions are not measurable unless they show clear radiographic progression after radiotherapy.
  • The physical status score of the Eastern Cancer Collaboration Group (ECOG) is 0 or 1.
  • Life expectancy≥12 weeks.
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  • All toxicities (except alopecia, fatigue, or peripheral neuropathy) from previous anticancer therapy must have returned to grade 1 or baseline levels prior to initiation of the investigational drug (NCI CTCAE 5th Edition).
  • The heart QTcF interval ≤450 ms in males or ≤ 470 ms in females.
  • Laboratory tests must meet the following criteria. the indicators could not be corrected by blood transfusion or hematopoietic stimulating factors for 14 days prior to the screening laboratory examination.
  • Hemoglobin ≥90 g/L
  • Platelet count ≥100 x 10^9/L
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
  • Total bilirubin ≤ 1.5 x upper limit of normal(ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0× ULN, ≤ 5.0× ULN for liver tumors
  • Creatinine clearance was > 50 mL/min according to Cockcroft-Gault formula
  • No alcohol, drug or substance abuse history in the last 1 year.
  • Fertile female patients should not breastfeeding and must have a negative pregnancy test result within 5 days before the start of treatment (positive urine pregnancy test result need to be confirmed by a serum pregnancy test)..
  • Fertile female and male participant must consent to the use of an effective contraceptive method with their partner (e.g. surgical sterilization or condom or diaphragm contraception combined with spermicidal gel or intrauterine device (IUD), etc.) from the start of the study until 6 months after the last treatment.
  • Voluntarily participate in this study, fully understand the relevant risks, have good compliance, and sign the informed consent.
  • phase II: cohort expansion phase
  • Male or female, ≥ 18 years old.
  • Advanced HCC that is pathologically confirmed and cannot be controlled by surgical resection or local treatment.
  • Prior treatment with standard systemic therapies, including but not limited to sorafenib and/or systemic chemotherapy containing oxaliplatin, lenvatinib, regorafenib and/or opdivo, disease progression, toxic intolerance or refusal to continue treatment with these drugs.
  • At least one measurable lesion that meets RECIST 1.1 criteria. Lesions previously treated with radiotherapy are not measurable unless confirmed radiographic progression.
  • Can provide pathological wax blocks or sections (including archived pathological wax blocks or sections) for AKR1C3 expression analysis, and be confirmed that AKR1C3 expression is strongly positive in liver tumor tissues (the proportion of tumor cells with AKR1C3 staining intensity of 2+ and/or 3+ is ≥70%, confirmed by the central laboratory using immunohistochemistry).
  • The physical status score of the Eastern Cancer Collaboration Group (ECOG) is 0 or 1.
  • Life expectancy≥12 weeks.
  • With or without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  • Participant with HBV infection must have HBV-DNA < 2,000 IU/ml and receive antiviral therapy with Entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide fumarate, according to National Guidelines for Chronic Hepatitis B Prevention and Treatment, maintained during the study period and continued until 6 months after the last dose.
  • Participant with coexisting HCV infection (presence of detectable HCV-RNA or anti-HCV antibodies) can be treated according to medical practice.
  • Child-Pugh score≤6.
  • No history of hepatic encephalopathy.
  • All toxicities (except alopecia, fatigue, or peripheral neuropathy) from previous anticancer therapy must have returned to grade 1 or baseline levels before initiating investigational drug use (NCI CTCAE 5th Edition).
  • Laboratory tests must meet the following criteria. The indicators could not be corrected by blood transfusion or hematopoietic stimulating factors or albumin infusion within 14 days before the screening laboratory examination.
  • Hemoglobin≥90 g/L
  • Platelet count≥80 x 10^9/L
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
  • Serum total bilirubin ≤3 mg/dL
  • ALT and AST ≤5.0 x ULN
  • International Normalized Ratio (INR) ≤2.3 or prolonged prothrombin time ≤6 seconds
  • Albumin≥29 g/L
  • Creatinine clearance > 50 mL/min as measured by Cockcroft-Gault equation
  • No alcohol, drug or substance abuse history in the last one year.
  • Fertile female patients should not breastfeeding and must have a negative pregnancy test result within 5 days before the start of treatment (positive urine pregnancy test result need to be confirmed by a serum pregnancy test).
  • Fertile female and male participant must consent to use effective contraceptive methods with their partner from the beginning of study participation (e.g., surgical sterilization or condom or diaphragm contraception combined with spermicidal gel or intrauterine device (IUD), etc.) until 6 months after the last treatment.
  • Voluntarily participate in this study, fully understand the risks involved, have good compliance, and sign informed consent. Participant may also sign a consent form for future biomedical research (FBR). However, participant who do not participate in the FBR may also participate in the principal trial.

Who cannot join

  • phase I: dose escalation phase
  • Untreated active central nervous system (CNS) metastases or leptomeningeal disease. Participant may participate in the study if their CNS metastases have been adequately treated and are stable for at least 4 weeks as confirmed by clinical examination and brain imaging (MRI or CT) during screening.
  • Major surgery other than diagnostic surgery was performed within 4 weeks prior to initial dosing.
  • Radiotherapy, surgery, chemotherapy, immunotherapy, cancer biotherapy, targeted therapy, or hormonal therapy within 4 weeks prior to the first dose (lomustine or mitomycin C treatment, requiring a 6-week washout period; Oral fluorouracil, requiring a 2-week washout period; Small molecule targeted therapy requires a 2-week washout period).
  • Participated in an investigational drug (diagnostic or therapeutic) or device study within 4 weeks prior to initial dosing.
  • Combined use of strong potent CYP3A4 inhibitors or inducers need to be used during the study.
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  • Uncontrolled, active bacterial, viral or fungal infections requiring systemic treatment.
  • Known to be positive for human immunodeficiency virus (HIV) or syphilis.
  • Women who are pregnant, breast-feeding, or planning to become pregnant.
  • Concomitant diseases or symptoms that may interfere with the conduct of the study, or physical abnormalities that the investigator believes pose an excessive risk to the patient, including but not limited to active peptic ulcer or gastritis, changes in mental status, or mental abnormalities that may interfere with the patient's understanding of the informed consent form.
  • Previous allergies to ethanol and propylene glycol.
  • Unwilling or unable to comply with the study protocol for any reason.
  • phase II: cohort expansion phase
  • Untreated active central nervous system (CNS) metastases or leptomeningeal disease. Participant may participate in the study if their CNS metastases have been adequately treated and are stable for at least 4 weeks as confirmed by clinical examination and brain imaging (MRI or CT) during screening.
  • A history of other malignancies within 2 years, except adequately treated basal cell carcinoma, carcinoma in situ at other sites, or other tumors whose natural history and treatment would not interfere with the evaluation of the safety and efficacy of the study.
  • Major surgery other than diagnostic surgery was performed within 4 weeks prior to initial dosing.
  • Radiotherapy, surgery, chemotherapy, immunotherapy, cancer biotherapy, targeted therapy, or hormonal therapy within 4 weeks prior to the first dose (lomustine or mitomycin C treatment, requiring a 6-week washout period; Oral fluorouracil, requiring a 2-week washout period; Small molecule targeted therapy requires a 2-week washout period).
  • Participated in an investigational drug (diagnostic or therapeutic) or device study within 4 weeks prior to initial dosing.
  • Combined use of strong potent CYP3A4 inhibitors or inducers need to be used during the study.
  • Uncontrolled, active bacterial, viral or fungal infections requiring systemic treatment.
  • Known active infection of human immunodeficiency virus (HIV) or syphilis.
  • Clinically significant ascites，defined as those detected by physical examination and requiring control by abdominal puncture or additional pharmacological intervention to maintain symptoms (patients whose ascites detected only by imaging examination are eligible).
  • Women who are pregnant, breast-feeding or planning to become pregnant.
  • Concomitant diseases or symptoms that may interfere with the conduct of the study, or physical abnormalities that the investigator believes pose an excessive risk to the patient, including but not limited to history of gastrointestinal bleeding or high risk of bleeding within three months, active peptic ulcer or gastritis, changes in mental status, or mental abnormalities that may interfere with the patient's understanding of the informed consent form.
  • Previous allergies to ethanol and propylene glycol.
  • Unwilling or unable to comply with the study protocol for any reason.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

China7 sites

  • Guangdong Qifu Hospital

    Guangzhou, Guangdong, 510000

  • Sir Run Run Shaw Hospital (SRRSH), affiliated with the Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310000

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang, 310000

  • Chinese People's Liberation Army Eastern Theater General Hospital Qinhuai medical District

    Nanjing, Jiangsu, 210000

  • Shanghai East Hospital

    Shanghai, Shanghai Municipality, 200000

  • The First Affiliated Hospital of China Medical University

    Shenyang, Liaoning, 110000

  • Henan Cancer Hospital

    Zhengzhou, Henan, 450000

Other trials in China

About this study

Official title: Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of AST-3424 in Treatment of Patients With Advanced Solid Tumors and Its Correlation With AKR1C3 Enzyme Expression

An open-label, Phase I/II study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of AST-3424 administered as a single agent

Read the detailed description

This is an open-label phase I/II clinical study to evaluate the safety, tolerability, MTD/RP2D, pharmacokinetics, preliminary efficacy, and the relationship between AKR1C3 expression and efficacy of AST-3424 monotherapy in advanced solid tumors.

The study is divided into phase I and Phase II. The maximum tolerated dose will be explored in phase I. In phase II, participants will be treated with AST-3424 according to the Phase I confirmed dose. Phase II clinical study will first be conducted in hepatocellular carcinoma (HCC).

Being tested
AST-3424
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • AST-3424Drug

    liquid formulation for Intravenous infusion

Study groups in NCT06239155
Study groupRoleWhat they receive
Phase I: dose escalation phaseExperimentalAST-3424 (1.0 mg/m^2 to 10.0 mg/m^2 or higher doses) will be administered by IV infusion on Day1 and Day8 of each 21-day cycle. 1mg/m^2 and 2mg/m^2 cohort will enroll 1 participant respectively . 4mg/m^2 or higher dose cohorts will use 3+3 dose escalation design to determine the MTD and RP2D.
Receives: Drug: AST-3424
Phase II: cohort expansion phaseExperimental6mg/m^2, administrated on Day1 and Day 8 of each 21-day cycle
Receives: Drug: AST-3424

What is being measured

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

  1. Incidence and severity of adverse events(AEs)

    Adverse events will be noted and graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0 or severity (if not covered by CTCAE)

    Measured: measure begins from informed consent to 30 days after last dose of study drug.

  2. Safety changes in electrocardiogram (ECG)

    Resting 12-lead ECGs will be obtained from all subjects' pre-AST-3424 infusion and within 30 minutes post-AST-3424 infusion in order to assess any impact AST-3424 may have on the QT interval as assessed by the Fridericia's Correction Formula (QTcF).

    Measured: Day 1 Cycles 1 and 2 (each cycle is 21 days)

  3. Safety Changes of body weight

    If during treatment a participant's body weight changes by >10%, the dose should be adjusted.

    Measured: Day 1 of each cycle (there are 34 cycles; 21 days for each cycle)

  4. Dose limiting toxicities (DLTs) in phase I

    Number of participants with dose limiting toxicities (DLTs)

    Measured: Throughout Cycle 1 (21 days for each cycle) in phase I (dose escalation phase).

  5. Maximum Tolerated Dose(MTD)/Recommended Phase 2 Dose (RP2D) in phase I

    Determination of the MTD, based on the frequently of DLTs observed in Cycle 1 in participants enrolled to the Dose Escalation Phase.

    Measured: Day 1 and Day 8 of each cycle (all 34 cycles and there are 21 days for each cycle)

  6. Pharmacokinetics (PK) - Time to maximum concentration (Tmax)

    Tmax of AST-3424 and AST-2660 will be computed for each subject where possible.

    Measured: Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

  7. PK - Maximum peak plasma concentration (Cmax)

    Cmax of AST-3424 and AST-2660 will be computed for each subject where possible.

    Measured: Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

  8. PK - The magnitude of the slope of the linear regression of the log concentration vs. time profile during the terminal phase (Kel)

    Kel of AST-3424 and AST-2660 will be computed for each subject where possible.

    Measured: Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

  9. PK - Half-life (T1/2)

    T1/2 computed as ln (2)/Kel of AST-3424 and AST-2660 will be computed for each subject where possible.

    Measured: Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

  10. PK - Area under the concentration-time curve (AUClast)

    AUClast from Hour 0 through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn

    Measured: Days 1 and 8 of Cycle 1(first cycle of 34 cycles and there are 21 days for each cycle)

  11. Objective response rate(ORR)

    Measured: Approximately 36 months

  12. Disease control rate(DCR)

    Measured: Approximately 36 months

  13. Duration of response (DOR)

    Measured: Approximately 36 months

  14. Progress free survival (PFS)

    Measured: Approximately 36 months

Timeline

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

  1. First posted2 Feb 2024
  2. Study start3 Sep 2019
  3. Primary completion30 Nov 2025 (estimated)
  4. Study completion30 Nov 2025 (estimated)

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
Sequential
Masking
None (open label)
Enrolment
51 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06239155
Sponsor's protocol ID
AST-3424-001
Status last verified
Feb 2025
First submitted
16 Jan 2024
Last updated
25 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AST-3424 in people with Advanced Solid Tumors and Hepatocellular Carcinoma, run by Ascentawits Pharmaceuticals, Ltd at 7 sites in China.

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 46 inclusion and 26 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: under way, not looking for participants, as of the sponsor's last update on 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in China. 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?

This study is still under way. Results are not available in the source record yet.

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?

Incidence and severity of adverse events(AEs) (time frame: measure begins from informed consent to 30 days after last dose of study drug.). The study lists 14 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 NCT06239155.

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 25 Feb 2025.

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