A Phase Ib / IIA Study of AL8326 in Small Cell Lung Cancer

NCT04890795 | Unknown Phase 1

• 1 other identifier: AL8326-CN-004
• Study Type: interventional
• Target: 237
• Locations: 1 country
• Sites: 9

Brief Summary

Based on indicators such as 24 week progression free survival (24 weeks PFS) in small cell lung cancer (SCLC) patients without disease progression after first-line platinum containing chemotherapy, objective response rate (ORR) in SCLC patients with recurrence or progression after first-line platinum containing chemotherapy, and orr in SCLC patients with recurrence or progression after second-line and above treatment,Evaluation of the effectiveness of al8326 monotherapy in small cell lung cancer.

Conditions

Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• (Group A) 24 weeks progression free survival (24 weeks PFS)

  Objective to evaluate the 24 week progression free survival (24 weeks PFS) of AL8326 in patients with small cell lung cancer (SCLC) without disease progression (PR or CR or SD) after first-line platinum based chemotherapy.

  Every 2 cycles(each cycle is 28--days)

• (Group B and C) Objective response rate (ORR)

  Objective response rate (ORR) of SCLC patients with recurrence or progression after first-line platinum chemotherapy, and objective response rate (ORR) of SCLC patients with recurrence or progression after second-line or above treatment.

  Every 2 cycles(each cycle is 28--days)

Secondary Outcomes (1)

• Safety and tolerance(Number of participants with treatment-related adverse events as assessed by CTCAE v5.0)

  Every 2 cycles(each cycle is 28--days)

Study Arms (1)

AL8326

EXPERIMENTAL

Subject will received AL8326 once daily for 28-days cycle until intolerable toxicity or disease progression or death or voluntary withdrawal the end of this study.During treatment, subjects will be evaluated for anti-tumor efficacy and corresponding safety examinations every 2 cycles, and tumor disease status will be according to RECIST 1.1.

Drug: AL8326 tablets

Interventions

AL8326 tablets DRUG

10mg/tablet;Oral administration, once daily.

Also known as: AL8326

AL8326

Eligibility Criteria

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

You may qualify if:

• All subjects or legal surrogates were required to give written, ethics committee approved informed consent prior to initiation of any screening procedures;
• Age ≥ 18 years, both genders, patients with histologically confirmed SCLC, and fulfilling the following criteria:
• Group A: Patients with small-cell lung cancer without disease progression (in remission \[PR or Cr\] or stable disease \[SD\] status according to RECIST 1.1 criteria) after first-line platinum containing chemotherapy, including extensive stage and limited stage who were not eligible for radical radiotherapy, received four to six cycles of platinum containing chemotherapy previously; Group B: Patients with small-cell lung cancer who have relapsed or progressed after first-line platinum containing chemotherapy regimens; Group C: Patients with small cell lung cancer who have relapsed or progressed after at least one line of therapy (including first-line platinum containing therapy, second-line single agent therapy, or other);Notes: platinum containing chemotherapy regimens included etoposide + cisplatin, etoposide + carboplatin, irinotecan + cisplatin, irinotecan + carboplatin, etoposide + lobaplatin;Second line monotherapy regimens include topotecan, irinotecan, paclitaxel, docetaxel, gemcitabine, oral etoposide, vinorelbine, temozolomide, ifosfamide;Second line and beyond other treatments include small molecule targeted agents, monoclonal antibodies, etc.
• ECOG (PS) score was 0,1;
• Life expectancy ≥ 12 weeks;
• Subjects in arm B / C had at least one measurable tumor lesion according to response evaluation criteria in solid tumors (RECIST 1.1;
• The subject had adequate organ and bone marrow function meeting the following laboratory test criteria:
• Bone marrow function: absolute neutrophil count (ANC) ≥ 1.5×10\^9 / L (1500 / mm\^3), platelets ≥ 80×10\^9/L;
• Hemoglobin ≥ 9.0 g / dl;Liver function: serum total bilirubin ≤ 1.5 times the upper limit of normal (ULN), with the exception of patients with Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that manifests as elevated unconjugated bilirubin in the absence of evidence of hemolysis or liver pathology);
• Those without liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN, those with liver metastases, ALT and AST ≤ 5×ULN;
• Renal function: serum creatinine ≤ 1.5×ULN and a standard endogenous creatinine clearance ≥ 60 ml / min estimated by the Cockcroft Gault formula, CCR (ml / min) = \[(140 - age)×Weight (kg)\] / \[72× SCR (mg / dl)\], females as calculated×0.85;
• Coagulopathy: international normalized ratio (INR) ≤ 1.5;
• Hemodynamically stable and left ventricular ejection fraction (LVEF) ≥ 50% as determined by echocardiography;
• Previous treatment with cytotoxic chemotherapy, traditional Chinese medicine, ending at least 4 weeks apart from first dose, receipt of nitroso or mitomycin at least 6 weeks apart, and TKI class molecularly targeted agents at least 4 weeks apart and having recovered to grade ≤ 1 from the toxic effects of previous chemotherapy, with the following exceptions: a.alopecia;b. Long term toxicity caused by radiotherapy, which could not be recovered after the judgment of the investigator;c. Platinum induced grade 2 and the following neurotoxicity such as hearing impairment (according to common terminology criteria for adverse events CTCAE V5.0);
• Women of childbearing age and all male subjects must agree to use highly effective methods of contraception (condoms, contraceptive sponges, contraceptive gels, contraceptive membranes, IUDs, oral or injectable contraceptives, subcutaneous implants, etc.) for the duration of the study and for 3 months after discontinuation.

You may not qualify if:

• Patients who had used AL8326 tablets in the past;
• Allergic to AL8326 or its analogues, or to any component in the prescription of AL8326;
• The patients with leptomeningeal history or leptomeningeal metastasis or central nervous system (CNS) metastasis at the time of screening had uncontrollable brain metastasis, spinal cord compression and cancerous meningitis within 8 weeks after the first medication, Patients with CNS metastasis or spinal cord compression whose clinical status is stable and does not need corticosteroid treatment and whose screening time is more than 4 weeks before treatment (including radiotherapy or surgery) are excluded;
• Patients with current or previous second tumor (except for fully treated basal cell carcinoma of skin or squamous cell carcinoma, cervical carcinoma in situ), unless radical treatment has been carried out and there is no evidence of recurrence and metastasis in the past 5 years;
• Those who have obvious gastrointestinal history or current diseases, such as inability to swallow, severe peptic ulcer, uncontrollable nausea and vomiting, chronic diarrhea, intestinal obstruction or other chronic gastrointestinal diseases that are difficult to control in recent 3 months, inability to swallow drugs or may affect the intake, transportation or absorption of drugs, or who have undergone total gastrectomy before;
• Patients with other important primary diseases, such as single drug uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and / or diastolic blood pressure ≥ 100 mmHg), arrhythmias that need clinical intervention (such as long QT syndrome, unmeasurable bazetts corrected QTc or male \> 450 ms, female \> 470 MS), abnormally prolonged arrhythmias caused by unstable coronary artery disease Patients with decompensated congestive heart failure (NYHA grade III or IV) or myocardial infarction, grade 2 or above thyroid disease, ascites or uncontrolled pleural effusion (CTCAE 5.0 ≥ 2), history of thrombosis or stroke, autoimmune disease, and mental illness within 6 months before administration of the test drug;
• The patients with arteriovenous thrombotic events such as cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism in the first 6 months were screened;
• The tumor had invaded the important blood vessels or the researchers judged that the tumor was likely to invade the important blood vessels during the follow-up study and cause fatal massive hemorrhage;
• Uncontrolled infection (within 2 weeks before the administration of the test drug);
• Urine routine examination showed that urine protein was ≥ + +, and 24-hour urine protein was more than 1.0 G;
• The patients with grade 1 or more bleeding events (according to CTCAE 5.0 \> grade 1), including gastrointestinal tract, respiratory system, tumor, urinary tract and cerebral hemorrhage, were screened;
• Patients treated with anticoagulants or vitamin K antagonists (such as warfarin, heparin or their analogues); Under the premise of prothrombin time international normalized ratio (INR) ≤ 1.5, it is allowed to use low-dose anticoagulants for preventive purposes, such as warfarin (not more than 1 mg daily, oral), low-dose heparin (not more than 12000 u daily) or low-dose aspirin (not more than 100 mg daily);
• Hepatitis C virus (HCV) antibody, Treponema pallidum antibody or human immunodeficiency virus (HIV) antibody test results of any one or more positive, or active hepatitis B patients (defined as HBV DNA ≥ 2000 IU / ml or HBV DNA ≥ 104 copies);
• Patients who received any trial drug treatment within 30 days before signing the informed consent form;
• Patients who received red blood cell or platelet transfusion within 14 days before the first administration;

Sponsors & Collaborators

• Advenchen Laboratories Nanjing Ltd.: lead

Study Sites (9)

The first affiliated hospital of bengbu medical college

Bengbu, Anhui, 233000, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450000, China

RECRUITING

General Hospital of Eastern Theater Command

Nanjing, Jiangsu, 210000, China

RECRUITING

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221000, China

RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266000, China

RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Sichuan Cancer Hospital

Chengdu, Sichuan, 610000, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• xiaochun Zhang

  The Affiliated Hospital of Qingdao University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

yingyin Li

CONTACT

+8657188683590; annel@advenchen.com

He Huaqing

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: October 19, 2020
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: May 18, 2021

Record last verified: 2021-05

Locations

CN (9)