A Phase 3 Study to Evaluate the Safety and Efficacy of APL-1202 as a Single-agent Oral Treatment Versus Intravesical Instillation of Epirubicin Hydrochloride in naïve Intermediate-risk NMIBC Patients (ASCERTAIN)

  • STATUS
    Recruiting
  • End date
    Dec 31, 2025
  • participants needed
    800
  • sponsor
    Jiangsu Yahong Meditech Co., Ltd aka Asieris
Updated on 15 March 2022

Summary

A multi-center, randomized, open-label, parallel-controlled Phase Ⅲ clinical trial to evaluate the clinical safety and efficacy of APL-1202 as a single-agent oral treatment versus intravesical instillation of Epirubicin hydrochloride in naïve intermediate-risk non-muscle invasive bladder cancer (NMIBC) patients

Description

A multi-center, randomized, open-label, placebo controlled Phase Ⅲ trial. The subjects must be histopathologically diagnosed, naïve intermediate-risk NMIBC patient. The screening period is 6 weeks prior to treatment.

The trial including 2 stages:

• First stages: The subjects are randomly assigned to receive APL-1202 single-agent oral treatment or intravesical instillation of Epirubicin hydrochloride at a ratio of 1:1. At this stage, an interim analysis will be performed after the first 100 subjects enrolled completing the 6-month visit (completing the second cystoscopy), and the Independent Data Monitoring Committee (IDMC) conducted a preliminary evaluation of the safety. If approved by the IDMC after the safety evaluation, the trial will proceed to the second stage. Before the result of the interim analysis are obtained, subjects receiving APL-1202 will continue to be given continuous administration if they have completed the 6-month visit (V4). After the interim analysis, if the safety of continuous administration is as expected, subjects receiving APL-1202 will continue to do the same, otherwise it will be adjusted to the administration of APL-1202 at every 3-month interval which is proven to be safe and tolerable.

• Second stage: After the interim analysis of the first stage, the subjects of the second stage will be enrolled, and the subjects were randomly assigned to receive APL-1202 single-agent oral treatment or intravesical instillation of Epirubicin hydrochloride at a ratio of 1:1. For treatment, according to the results of the interim analysis, if the safety of continuous administration reaches the expected level, subjects receiving APL-1202 will continue to do the same, otherwise it will be adjusted to the administration of APL-1202 at every 3-month interval which is proven to be safe and tolerable.

In this trial, the APL-1202 dosing regimen will continue until subjects exit the trial early for any reason, complete 24 months' treatment or the trial is terminated early.

Cystoscopy will be performed every 3 months in the enrolled subjects. If there is no recurrence in the enrolled subject during the treatment period (2 years after enrollment), cystoscopy will be performed every 6 months during the follow-up period until recurrence or the end of the clinical trial.

Safety assessment will be performed every 3 months during the treatment period.

Details
Condition Non-muscle Invasive Bladder Cancer
Treatment epirubicin hydrochloride, APL-1202
Clinical Study IdentifierNCT04736394
SponsorJiangsu Yahong Meditech Co., Ltd aka Asieris
Last Modified on15 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

All patients must meet all the following criteria
Must be informed of the investigational nature of this study and must provide written informed consent
Age ≥18 years, male or female
Non-muscle invasive transitional cell carcinoma of the bladder is histologically confirmed by Independent Pathology Review Committee (IPRC). Diagnosis and classification of intermediate-risk NMIBC is according to 2014 CUA Guideline of Diagnosis and Treatment of Urological Diseases in China
Low-risk: Primary, solitary, TaGl (PUNLMP, low-grade urothelial carcinoma), <3cm, no CIS
(Note: the above conditions must be met at the same time as a low-risk NMIBC)
Intermediate-risk: All tumours not defined in the two adjacent categories (between the
category of low and high risk) High-risk: Any of the following: ① T1 tumour; ②G3(high-grade
urothelial carcinoma) tumour;③carcinoma in situ (CIS); ④ Multiple, recurrent and large (> 3
cm) TaG1G2(low-grade urothelial carcinoma) tumours (all features must be present)
• No visible tumor after transurethral resection of bladder tumor (TURBT) on tumor lesion
Some requirements about Re-TURBT are as follows: It is recommended to conduct the secondary
TURBT under following situations: incomplete first TURBT; no muscle tissue found in the
first TURBT specimen, except Ta G1 (low grade) tumor and CIS only
The secondary TURBT is recommended 2-6 weeks, but better at 4 weeks, after the first TURBT
For subjects undergoing secondary TURBT, they will be enrolled after the second TURBT
Subjects who never received intravesical instillation (including BCG or intravesical
chemotherapy) prior to enrollment, except single, immediate, post-operative
intravesical chemotherapy
Willing to provide pathological tissue specimen for assessment
ECOG PS ≤ 1
Patients, who have not received blood transfusion or colony-stimulating factor
treatment within 14 days before the examination, must have normal organ and marrow
function within 42 days of study entry (according to normal range in clinical site)
Absolute neutrophil count >1.5×109/L Platelets > 100 ×109/L Hemoglobin > 9.0 g/dL Alkaline
phosphatase < 2.5 ULN GFR (Cockcroft-Gault formula calculated) ≥ 50 mL/min Total bilirubin
alanine aminotransferase or aspartate aminotransferase< 1.5 ULN INR <1.5, except for
subjects receiving anticoagulation therapy
Female should be either surgically sterilized or menopause or agree to use effective
contraceptive measures during treatment. Women of reproductive age must have a
negative result of pregnancy test during the screening period (pregnancy test will be
not required if one of the following situations exists: the subject has undergone
sterilization such as hysterectomy and/or bilateral oophorectomy, has no menstruation
for 12 months and been diagnosed as menopause based on factors such as age). However
pregnancy tests are required for patients with bilateral fallopian tube ligation
Male subjects should be either surgically sterilized or agreed to use effective
contraceptive measures. From signing the informed consent, subjects must take
continuous measures until 3 months after the end of the treatment of trial. The
definition of effective contraceptive measures will be based on the principal
investigator(PI) or appointed delegate
Expected life expectancy is more than 48 months

Exclusion Criteria

The presence of any of the following will exclude a patient from study enrollment
Low-risk: Primary, solitary, TaGl (PUNLMP, low-grade urothelial carcinoma), <3cm, no
CIS. (PS: the above conditions must be met at the same time as a low-risk NMIBC)
High-risk: Any of the following: ① T1 tumour; ②G3(high-grade urothelial carcinoma)
tumour;③carcinoma in situ (CIS); ④ Multiple, recurrent and large (> 3 cm)
TaG1G2(low-grade urothelial carcinoma) tumours (all features must be present)
Tumors of T2 stage or more serious
The histological types are mainly non-urothelial carcinomas such as squamous cell
carcinoma and adenocarcinoma
Urothelial carcinoma outside the bladder (renal pelvis, ureter or urethra)
Received intravesical therapy in last TURBT/cystoscopy prior to treatment period, but
not including immediate intravesical therapy once (the subjects who received the
immediate intravesical therapy need to be recorded in e-CRF)
Received surgery (not includes TURBT/cystoscopy), radiation therapy, or systemic
therapy within 6 weeks before enrollment
Malignancies within 2 years with exception of currently treated basal cell, squamous
cell carcinoma of the skin, or carcinoma "in-situ' of the cervix
Grade 3 (according to the NCI CTCAE 5.0) hemorrhage in any part of body within 6 weeks
before starting the treatment of trial
Any of the following within 6 months prior to study drug administration: myocardial
infarction, severe/unstable angina, coronary/peripheral artery bypass graft
symptomatic congestive heart failure, cerebrovascular accident or transient ischemic
attack, or pulmonary embolism
Hypertension that cannot be controlled by medications (systolic blood pressure≥140
mmHg and/or diastolic blood pressure≥90mmHg)
Uncontrolled active infections before starting the treatment of trial, such as acute
pneumonia, active hepatitis B, etc
Dysphagia or known drug absorption disorders
Anuria
One week prior to enrollment, having gross hematuria
Active duodenal ulcers, ulcerative colitis and other gastrointestinal diseases or
other conditions that the investigator may determine to cause gastrointestinal
bleeding or perforation
The risk of participation or administration may increase, judged by investigator, or
other severe acute or chronic medical conditions may interfere with the interpretation
and judgment of results
or optic nerve disorders
Subjects have optic nerve disorders and cataracts, or other related medical history
Pregnancy or breastfeeding. Female patients with reproductive potential have a
positive pregnancy test prior to enrollment
Psychological or mental abnormality, subjects are estimated to have insufficient
adherence to this clinical study
Four weeks prior to enrollment, participate in other clinical trials
Patients who had previously received anthracycline for systemic chemotherapy
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