A Study on the Safety and Efficacy of LAE001 in the Treatment of Metastatic Prostate Cancer

NCT03843918 | Terminated Phase 1

• 1 other identifier: LAE001CN2101
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a multicenter phase I/II study of the treatment of patients with metastatic prostate cancer. The objective of Phase I part is to study the safety and tolerability of LAE001 monotherapy in patients with metastatic castration-resistant prostate cancer, and determine the maximum tolerated dose (MTD) as well as the recommended phase II dose (RP2D) of the drug, the Phase II part is to assess the efficacy of LAE001 based on PSA in the treatment of patients with metastatic castration-resistant prostate cancer.

Conditions

Prostate Cancer Metastatic

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of DLT (Phase I)

  To study the incidence of DLT in the first cycle of administration

  up to 28 days

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  To describe the incidence and severity of adverse events as assessed by CTCAE Version 5.0

  through phase I part of study completion, an approximate average of 7 months

Secondary Outcomes (18)

• 12-week PSA response rate

  12 weeks after randomization

• Overall response rate (ORR)

  through study completion, an approximate average of 7 months

• Pharmacokinetic: Cmax

  through phase I part of study completion, an approximate average of 7 months

• Changes in Testosterone Levels

  through phase I part of study completion, an approximate average of 7 months

• Radiographic progression-free survival (rPFS) (Phase II)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, approximately up to 35 months

Study Arms (1)

LAE001+ADT

EXPERIMENTAL

LAE001+ADT

Drug: LAE001

Interventions

LAE001 DRUG

LAE001 BID will be orally administered until the subjects develop disease progression, intolerable adverse events, or trial withdrawal decided by the investigator/subject. The LAE001 dose adopted for the phase II study will be based on the RP2D determined in the phase I study.

Also known as: CFG920

LAE001+ADT

Eligibility Criteria

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

You may qualify if:

• Understands the trial procedures and content, and voluntarily signs the written informed consent form.
• Male ≥ 18 years old.
• Prostate adenocarcinoma as confirmed by histology or cytology, excluding neuroendocrine differentiation, signet ring cell carcinoma, and small cell carcinoma.
• Evidence (such as bone scan or CT/MRI findings) of distant metastatic disease.
• Phase I: According to the definition by PCWG3, disease progression after androgen deprivation therapy is as follows:
• Disease progression, as defined by PCWG3, is the satisfaction of any of the following: According to elevations in PSA levels, there should be two consecutive elevations in PSA at least one week apart (if the third detected value is greater than the second detected value, the disease is determined to have progressed; if the third detected value is smaller than the second detected value, a fourth test is required to determine whether the PSA value is greater than the second detected value, and the interval between each test shall be at least one week), and the minimum value shall be equal to or greater than 1.0 ng/mL; PSA levels can be ignored for disease progression as assessed according to RECIST 1.1; progression of bone disease as defined by PCWG3, that is, the discovery of two or more new lesions via bone scan.
• ECOG score of 0-1.
• Dose-escalation phase: Patients with metastatic castration-resistant prostate cancer who have not received chemotherapy or who have received chemotherapy (chemotherapy failure or intolerance), with preferential enrollment of patients who had failed chemotherapy.
• Phase II: Patients with metastatic castration-resistant prostate cancer • ECOG score of 0-1.
• Allow other previous treatment for mCRPC: Up to 1 cycle of palliative radiotherapy or surgical intervention to control the appearance of prostate cancer. Radiotherapy for the purpose of healing is not allowed. Radiation therapy must be completed at least 2 weeks before the first dose..
• The subject underwent orchiectomy, or LHRH agonist or antagonist therapy before enrollment, and the therapy will be maintained throughout the entire study. The patient was at castration level during screening, i.e., his testosterone level was \< 50 ng/dL or 1.7 nmol/L.
• Adequate hematopoietic function:
• o White blood cell count, WBC ≥ 3,000/μL
• Absolute neutrophil count, ANC ≥ 1,500/μL
• Platelet count ≥ 100,000/μL

You may not qualify if:

• Patients who had been treated with abiraterone acetate or enzalutamide.
• Phase I: Patients who received anti-tumor therapy such as chemotherapy, radiotherapy, targeted therapy, and endocrine therapy with androgen receptor inhibitors within four weeks prior to the first dose (the time from the last treatment with nitrosourea or mitomycin chemotherapeutic agents is \< 6 weeks, and the time from the last dose of bicalutamide or nilutamide is \< 6 weeks).
• Phase II: Patients who received any chemotherapy, radiotherapy or surgery for metastatic prostate cancer before randomization. Exceptions: ADT therapy (LHRH agonist or orchiectomy) before Day 1 of Cycle 1. Or \>4 weeks since last use of bicalutamide or other generation antiandrogen receptor antagonist (please confirm with sponsor). Subjects may receive a course of palliative radiotherapy or surgery to treat symptoms caused by metastatic disease (e.g. spinal cord compression or obstruction), provided that it is administered at least 28 days prior to Day 1 of Cycle 1. All adverse events associated with such treatment must be alleviated to Grade 1 by Day 1 of Cycle 1.
• Patients who underwent major surgery (major surgery refers to Grade 3 and Grade 4 surgery as defined in the "Administrative Measures for Clinical Application of Medical Technologies" promulgated on May 01, 2009) within 28 days before the study treatment, or who have not fully recovered from surgery (the investigator determines that the patient's participation in the clinical trial would pose a risk).
• Patients with known severe cardiovascular diseases, including: myocardial infarction or thrombotic events in the past six months; unstable angina; heart failure of Class III or IV according to the criteria of the New York Heart Association (NYHA); QTc interval (QTcF) \> 450 ms during the screening visit; G3 hypertension that cannot be controlled even with standard treatment, systolic blood pressure \>160 mmHg or diastolic blood pressure\>100 mmHg).
• Patient who have not yet recovered from the toxicity of the former treatment regimen before drug administration on Day 1 of Cycle 1, and still have toxic reactions (excluding hair loss) above Grade 1 according to the grading scale of version 5.0 of the Common Terminology Criteria for Adverse Events (CTCAE).
• Patients with clinically obvious gastrointestinal abnormalities that may affect the intake, transportation or absorption of drugs (such as patients who are unable to swallow, have chronic diarrhea or intestinal obstruction, or who had undergone total gastrectomy).
• Patients with visceral metastasis involving the adrenal glands and central nervous system.
• Patients with evidence of myelosuppression, and hydronephrosis in both kidneys as well as bladder neck obstruction that affects kidney function
• Type I diabetes and type II diabetes that cannot be controlled by medication
• Patients with a history of severe central nervous system diseases, including epilepsy.
• Patients who had other malignant tumors (except for basal or squamous cell carcinoma) in addition to prostate cancer in the past five years, which are currently clinically significant and require intervention.
• Patients who received 5α-reductase inhibitors (finasteride, dutasteride), estrogen, cyproterone and other drugs for treatment within four weeks before the first dose, and whose period of drug discontinuation has not exceeded five half-lives of the corresponding drugs; the drugs must have been discontinued for more than two weeks if the half-life is unknown.
• Male patients whose sexual partners are women of childbearing age, where the patient and / or his sexual partner do not agree to use highly effective contraceptive measures (i.e. contraceptives with a low failure rate (less than or equivalent to 1% per year) when used consistently and correctly), and continued use of such measures until four weeks after drug discontinuation.
• Patients who require systemic steroids or who had received systemic steroids (more than or equivalent to 10 mg of prednisone per day) 30 days before enrollment; topical, inhaled, ophthalmic or intra-articular medications are acceptable.

Sponsors & Collaborators

• Laekna Limited: lead

Study Sites (2)

Fudan Cancer Hospital

Shanghai, Shanghai Municipality, China

Location

ZheJiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Dingwei Ye, MD

  Fudan University Shanghai Cnacer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Phase I: Open label; Phase II: Open label;
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase I: 3+3 design for dose escalation Phase II: designed as a single arm, multicenter trial

Study Record Dates

• First Submitted: January 29, 2019
• First Posted: February 18, 2019
• Study Start: April 5, 2019
• Primary Completion: October 9, 2023
• Study Completion: October 9, 2023
• Last Updated: September 10, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)