A Phase I Study of AL8326 in Advanced Solid Tumor

NCT04890587 | Unknown Phase 1

• 1 other identifier: AL8326-CN-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

1. 1.Main purpose Objective to study the tolerance and safety of single and multiple administration of repeated 28-day cycles of AL8326 in patients with advanced solid tumor, observe the dose limiting toxicity (DLT) and maximum tolerated dose (MTD).
2. 2.Secondary purpose 1) Preliminary analysis of the pharmacokinetic characteristics and efficacy of repeated 28-day cycles of AL8326 tablets in patients with advanced solid tumors; 2) According to the results of phase I tolerance test and pharmacokinetics, appropriate dosage and regimen were recommended for phase II clinical trial;

Conditions

Advanced Solid Tumors

Keywords

Maximum tolerated dose; Dose limiting toxicity

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT)

  To observe the durability and safety of AL8326 in patients with advanced solid tumor after single and multiple administration, observe the dose limiting toxicity (DLT)and the reversibility of toxicity;

  cycle1 (each cycle is 28-days)

• Maximum tolerated dose (MTD)

  To observe the durability and safety of AL8326 in patients with advanced solid tumor after single and multiple administration, observe the maximum tolerated dose (MTD)，the relationship between toxicity and dose;

  cycle1 (each cycle is 28-days)

Secondary Outcomes (9)

• Cmax

  cycle1 (each cycle is 28-days)

• Tmax

  cycle1 (each cycle is 28-days)

• AUC0-t

  cycle1 (each cycle is 28-days)

• AUC0-∞

  cycle1 (each cycle is 28-days)

• Vd

  cycle1 (each cycle is 28-days)

Study Arms (1)

AL8326

EXPERIMENTAL

Part 1:(closed)Cohort 1 will initiate with AL8326 for single dose and multiple dose (28-Day cycles) . After three subjects have completed the first cycle of therapy without a DLT, additional cohorts may be enrolled sequentially. After the first cohort has completed one full cycle of therapy without a DLT, several additional cohorts will be sequentially for the same 28-day cycles. Part 2 :(open)Each subject will receive a dose from Part 1 of this study for continuous 28-Day cycles of therapy. Part 3:(open)Cohort 3 will initiate with AL8326(bid), for 28-Day cycles . After three subjects have completed the first cycle of therapy without a DLT, additional cohorts may be enrolled sequentially. After the first cohort has completed one full cycle of therapy without a DLT, two additional cohorts will be sequentially enrolled at decreased dose of AL8326 for the same 28-day cycles.

Drug: AL8326 tablets

Interventions

AL8326 tablets DRUG

Tablet:10mg/tablet; administered orally once daily in part 1 and part 2, administered orally twice daily for continuous 28-Day cycles in part 3.

Also known as: AL8326

AL8326

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with the following advanced solid tumors confirmed by histology or cytology (including but not limited to non-small cell lung cancer, cervical cancer, ovarian cancer, breast cancer, pancreatic cancer, liver cancer, colon cancer, head and neck cancer, prostate cancer, kidney cancer, etc.). Lack of effective standard treatment options; or failure (including disease progression or intolerance) or recurrence after conventional standard treatment.
• For subject received cytotoxic drugs chemotherapy before, the interval between the end of chemotherapy and the signing of informed consent was at least 4 weeks, and must be recovered from the toxic reaction of previous chemotherapy to ≤ 1 grade (except for hair loss);
• There must be at least measurable lesions in accordance with RECIST 1.1. If there is only one lesion, the lesion must be confirmed by cytology / histology.
• Main organ function:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10 \^ 9 / L (1500 / mm \^ 3), platelet ≥ 75 × 10 \^ 9 / L or hemoglobin ≥ 9g / dl.
• Serum total bilirubin ≤ 2 times the upper limit .
• Serum creatinine ≤ 1.5 times the upper limit of normal value or creatinine clearance rate ≥ 50ml / min.
• If there is no liver metastasis, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 times of the upper limit, or liver metastasis ≤ 5 times of the upper limit .
• Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ 50%.
• According to the judgment of the investigator, the laboratory examination results and clinical abnormalities that will not affect the safety of the subjects and the completion of the trial can be arranged into the group.
• ECOG (PS) score was 0,1;
• Life expectancy ≥ 12 weeks;
• Age ≥ 18 years old and ≤ 70 years old;
• There was no malabsorption or other gastrointestinal diseases affecting drug absorption.
• Female: for female patients with fertility, pregnancy test must be conducted before treatment, and contraceptive method approved by medical department must be adopted during treatment and within 3 months after treatment; serum or urine pregnancy test in screening period must be negative; it must be non lactation period; and；if a female patient is postmenopausal but has not yet reached the postmenopausal state (the duration of menopause is greater than or equal to 12 consecutive months, and there is no other reason except menopause), and has not received sterilization surgery (removal of ovaries and / or uterus), she is considered to be fertile.

You may not qualify if:

• It is known that it is allergic to drugs with similar chemical structure.
• Use of drugs or other trial drugs without approval within 30 days before enrollment.
• The condition of each organ system was as follows：
• Patients with previous history of central nervous system metastasis or uncontrollable symptoms of brain metastasis, spinal cord compression and cancerous meningitis within 8 weeks after the first administration. For patients with CNS metastasis or spinal cord compression, if the clinical status is stable and does not need hormone therapy, and the interval between the treatment (including radiotherapy or surgery) before entering the group is more than 4 weeks, they can participate in this trial.
• Grade 2 or above hypertension that cannot be controlled by single drug.
• Acute myocardial infarction occurred within 6 months.
• At present, there are arrhythmias (such as long QT syndrome, unmeasurable or ≥ 480ms of Bazett's corrected QTC).
• NYHA cardiac function grade III or IV.
• Evidence of severe or uncontrollable systemic disease (e.g., unstable or decompensated respiratory, heart, liver, or kidney disease), as judged by the investigators.
• Any unstable systemic disease (including active infection, angina pectoris, liver and kidney or metabolic disease, etc.).
• Other (primary) malignancies (except for completely cured cervical carcinoma in situ or basal cell carcinoma or squamous cell skin carcinoma) within five years.
• The presence of clinically detectable third space effusion (such as ascites or pleural effusion) requires immediate drainage. Or after treatment, the effusion is not well controlled and continues to increase.
• Previous history of definite neurological or mental disorders, such as epilepsy or dementia.
• The function level of each organ was as follows：
• The results of urine protein analysis showed that urine protein was ≥ + +, and 24-hour urine protein was more than 1.0 g.

Sponsors & Collaborators

• Advenchen Laboratories Nanjing Ltd.: lead

Study Sites (2)

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266000, China

RECRUITING

Study Officials

• Nong Yang

  Central organization

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yingyin Li

CONTACT

+8657188683590; annel@advenchen.com

Huaqing He

CONTACT

+8615205140516; huaqingh@advenchen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: May 18, 2021
• Study Start: August 17, 2017
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: May 18, 2021

Record last verified: 2021-05

Locations

CN (2)