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Non-muscle Invasive Bladder CancerPhase 2NCT04498702

Study of Continuous APL-1202 Treatment in Subjects With High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) Relapsed From Intravesical Chemo/BCG Therapy

A Phase 2 study testing APL-1202 treatment in people with Non-muscle Invasive Bladder Cancer, run by Jiangsu Yahong Meditech Co., Ltd aka Asieris.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To determine the efficacy of oral APL-1202 administered consecutively for 12 weeks in subjects with high-risk NMIBC relapsed from intravesical chemo/BCG therapy based on the recurrence-free rate (RFR) at 12 months after APL-1202 treatment. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-muscle Invasive Bladder Cancer
What is being tested?
APL-1202 treatment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
No sites listed yet
Study dates
13 May 2014to 18 Jan 2017
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Well-informed with this trial and willing to sign the informed consent form;
  • Subjects have been clinically and histologically proven as relapsed high-risk non-muscle-invasive urothelial carcinoma of the bladder through clinical cystoscopy, urine cytology and pathological examination within 28 days before the enrollment; Subjects who met the high-risk definition in EAU Guidelines on Non-Muscle-Invasive Bladder Cancer (2012 Edition), including those who met the high-risk definition in current or any previous recurrence or primary diseases; Papillary carcinomas may or may not include Cis; All papillary carcinoma subjects with no visible tumor after transurethral resection of bladder tumor (TURBT); May include Cis subjects with visible tumors remaining after TURBT;
  • Past treatment history:
  • Chemo-relapsed subgroup: the subjects who should have had intravesical chemotherapy in the 3 years prior to enrollment, but could not undergo any BCG therapy; BCG-relapsed subgroup: the subjects who should have had intravesical BCG treatment in the 3 years prior to enrollment, prior intravesical chemotherapy is allowed;
  • Subjects with treatment failure included:
  • Subjects with recurrence after at least one intravesical course; BCG-relapsed subjects might include those intolerable to intravesical BCG therapy; Subjects with tumor grade progression after intravesical therapy;
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  • The subject is willing to provide cystoscopic biopsy specimens for assessment
  • Age ≥ 18 years, male or female;
  • Performance status score (ECOG scale) ≤ 1 (0-1), and did not deteriorate within 7 days;
  • The subject must have normal organ and bone marrow functions within 28 days prior to enrollment into the study (based on normal range measured by the clinical site):
  • ANC > 1.0×109 /L; Platelet count > 100×109 /L; Hemoglobin > 9.0 g/dL; ALP < 2.5 times upper limit of normal range (should be less than 10 times upper limit of normal range if at the presence of bone metastasis); GFR (calculated using Cockcroft-Gault formula) ≥ 50 mL/min; INR < 1.5, except subjects who was undergoing Warfarin treatment at the time of screening.
  • Subjects who were receiving other medications with known or potential effects on the efficacy or pharmacokinetics of nitroxoline should be assessed and determined by the principal investigator.
  • Female subjects must be surgically sterilized or menopaused or must agree to take effective contraceptive measures during the treatment. Male subjects must be surgically sterilized or must agree to take effective contraceptive measures during treatment. Subjects must continue to take contraceptive measures for 3 months after the investigational therapy was completed. Definition of an effective contraceptive measure should be determined at the discretion of the principal investigator or any investigator appointed by the principal investigator.
  • Life expectancy is over 12 months.

Who cannot join

  • TBIL, ALT or AST exceeded 1.5 times upper limit of the normal range (based on the normal range determined by the clinical site);
  • Upper tract urothelial carcinoma;
  • Subjects who had systemic chemotherapy on bladder carcinoma in the past;
  • Subject who had undergone any surgical procedure (excluding TURBT or cystoscopy), radiotherapy or systemic chemotherapy within 4 weeks prior to enrollment;
  • Grade 3 hemorrhage as per NCI CTCAE 4.0 occurred within 4 weeks prior to enrollment;
  • Any of the following conditions occurred within 6 months prior to enrollment: myocardial infarction, serious/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism;
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  • Regardless of antihypertensive medication, systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg;
  • Subjects having a malignancy history within 2 years, except cured basal cell carcinoma, squamous cell skin cancer or cervical carcinoma "in situ";
  • Subjects with any optic nerve disorder or having a history of optic nerve disorders;
  • Subjects with clinically uncontrolled active infections such as acute pneumonia, immunoactive phase of hepatitis B, etc.;
  • Subjects with dysphagia or any known drug absorption disorder;
  • Subjects with anuria;
  • Subjects with any active digestive disease such as duodenal ulcer and ulcerative colitis or any other conditions potentially leading to gastrointestinal hemorrhage or perforation as identified by the investigator;
  • The investigator deemed that a subject might have increased risk for the study or medication or had any other serious acute or chronic medical conditions potentially interfering with interpretation and judgment of study results;
  • Any pregnant or breastfeeding woman or any woman with a positive pregnancy test results prior to the first medication;
  • Subjects having a serious mental disorder with compliance concern in this clinical study;
  • Subjects participating in any other clinical drug trial in the past 4 weeks.

About this study

Official title: A Phase II Single-Arm, Open-Label, Multi-Center Study of Continuous APL-1202 Treatment in Subjects With High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) Relapsed From Intravesical Chemo/BCG Therapy

To determine the efficacy of oral APL-1202 administered consecutively for 12 weeks in subjects with high-risk NMIBC relapsed from intravesical chemo/BCG therapy based on the recurrence-free rate (RFR) at 12 months after APL-1202 treatment.

Read the detailed description

This trial was a single-arm, open-label, multi-center clinical study consisting of two periods: the dose-escalation and treatment period, and the follow-up and maintenance period.

Dose-Escalation and Treatment Period APL-1202 was orally administered TID daily and continuously for 12 weeks. APL-1202 dose was increased from daily 300, 450, 600 to 750mg or maximum tolerated dose (MTD).

A modified 3+3 design was employed: The dose was started at 300 mg and increased to 450 mg, 600 mg and 750 mg if there was no dose-limiting toxicity (DLT) in 3 subjects after 4-week consecutive administration of APL-1202. When the dose-escalation study was in progress, the doses for any newly enrolled subjects would be the starting dose or the highest dose confirmed with no DLT by the dose-escalation cohort at the time of enrollment. When the MTD or the 750 mg daily dose was attained as a safe dose, the dose for all subjects in the study or subsequently enrolled subjects would be MTD or 750 mg/day.

Follow-up and Maintenance Period APL-1202 was orally administered at the highest safe dose proven by the dose-escalation cohort, continuously for 3 months; This period was 12 months. To fit the 3-month cystoscopy follow-up schedule, the maintenance therapy, starting from 3-month off, was given continuously every other 3 months, resulting in 6 months of dosing in total.

APL-1202 daily administration schedule:

The first dose: within 30 minutes after breakfast; The second dose: within 30 minutes after lunch, and there should be a 4-hour interval between the first and second doses; The third dose: taken with a light snack at night before going to bed.

Being tested
APL-1202 treatment
Medical subject headings
Non-Muscle Invasive Bladder Neoplasms

What participants receive

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

  • APL-1202 treatmentDrug

    A modified 3+3 design was employed: The dose was started at 300 mg and increased to 450 mg, 600 mg and 750 mg if there was no dose-limiting toxicity (DLT) in 3 subjects after 4-week consecutive administration of APL-1202. When the dose-escalation study was in progress, the doses for any newly enrolled subjects would be the starting dose or the highest dose confirmed with no DLT by the dose-escalation cohort at the time of enrollment. When the MTD or the 750 mg daily dose was attained as a safe dose, the dose for all subjects in the study or subsequently enrolled subjects would be MTD or 750 mg/day.

Study groups in NCT04498702
Study groupRoleWhat they receive
APL-1202 treatmentExperimentalNot described
Receives: Drug: APL-1202 treatment

What is being measured

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

  1. Recurrence-free rate (RFR) at the end of 12-month follow-up in subjects with high-risk NMIBC relapsed from intravesical chemo/BCG therapy.

    Recurrence-free rate (RFR) at the end of 12-month follow-up in subjects with high-risk NMIBC relapsed from intravesical chemo/BCG therapy.

    Measured: 12 months

Secondary outcomes (11)

  1. Recurrence-free survival (RFS)

    Recurrence-free survival (RFS)

    Measured: 12 months

  2. Progression-free survival (PFS).

    progression-free survival (PFS).

    Measured: 12 months

  3. The safety and tolerability of APL-1202.

    Post-medication safety assessment included laboratory parameters, physical examination, vital signs, performance status score, and AEs. Frequency and severity of AEs were rated in accordance with internationally agreed NCI CTC AE4.0.

    Measured: 12 months

  4. Plasma Max Concentration - APL-1202 and its metabolites

    PK measurement expressed as maximum plasma concentration for APL-1202 and metabolites

    Measured: Day 28

  5. Plasma Steady state Concentration - APL-1202 and its metabolites

    PK measurement expressed as Steady state Concentration for plasma APL-1202 and its metabolites

    Measured: Day 28

  6. Plasma Area Under Curve - APL-1202 and its metabolites

    PK measurement expressed as area under curve for plasma APL-1202 and its metabolites

    Measured: Day 28

  7. Urinary excreted amounts- APL-1202 and its metabolites

    PK measurement expressed as Urinary excreted amounts for APL-1202 and its metabolites

    Measured: Day 28

  8. Cumulative urinary excreted amounts- APL-1202 and its metabolites

    PK measurement expressed as Cumulative Urinary excreted amounts for APL-1202 and its metabolites

    Measured: Day 28

  9. Cumulative fraction of dose- APL-1202 and its metabolites

    PK measurement expressed as Cumulative fraction of dose for APL-1202 and its metabolites

    Measured: Day 28

  10. The SNV(single-nucleotide variant) patterns of bladder cancer related genes in pre- and post-treatment plasma ctDNA (circulating tumor DNA) through targeted amplicon sequencing

    Blood ctDNA were extracted from the patients before APL-1202 treatment or after APL-1202 treatment; somatic SNV were detected by targeted amplicon sequencing. Evaluation of RFR (Recurrence-free rate), RFS (Recurrence-free survival), PFS (Progression-free survival) and baseline SNV will be performed using cox regression survival model.

    Measured: 12 months

  11. The InDel (insertion-deletion) patterns of bladder cancer related genes in pre- and post-treatment plasma ctDNA (circulating tumor DNA) through targeted amplicon sequencing

    Blood ctDNA were extracted from the patients before APL-1202 treatment or after APL-1202 treatment; somatic InDel were detected by targeted amplicon sequencing. Evaluation of RFR (Recurrence-free rate), RFS (Recurrence-free survival), PFS (Progression-free survival) and baseline InDel will be performed using cox regression survival model.

    Measured: 12 months

Timeline

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

  1. First posted4 Aug 2020
  2. Study start13 May 2014
  3. Primary completion18 Jan 2017
  4. Study completion18 Jan 2017

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04498702
Sponsor's protocol ID
YHCT-1
Status last verified
Jul 2020
First submitted
22 Jul 2020
Last updated
13 Aug 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing APL-1202 treatment in people with Non-muscle Invasive Bladder Cancer, run by Jiangsu Yahong Meditech Co., Ltd aka Asieris.

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 14 inclusion and 17 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: finished, as of the sponsor's last update on 13 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

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 phase mean?

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Recurrence-free rate (RFR) at the end of 12-month follow-up in subjects with high-risk NMIBC relapsed from intravesical chemo/BCG therapy. (time frame: 12 months). 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 NCT04498702.

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 13 Aug 2020.

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