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Study of APL-1202 in Non-Muscle Invasive Bladder Cancer Patients Who Are Resistant to One Induction Course of BCG Treatment (NMIBC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03672240
Recruitment Status : Completed
First Posted : September 14, 2018
Last Update Posted : July 20, 2020
Sponsor:
Information provided by (Responsible Party):
AsierisPharma ( Asieris Pharmaceutical Technologies Co., Ltd. )

Tracking Information
First Submitted Date  ICMJE September 5, 2018
First Posted Date  ICMJE September 14, 2018
Last Update Posted Date July 20, 2020
Actual Study Start Date  ICMJE November 30, 2018
Actual Primary Completion Date October 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2018)
Incidence and Severity of Treatment-Related Adverse Events [ Time Frame: 13 weeks ]
Incidence and Severity of Treatment-Related Adverse Events as Assessed by CTCAE v.5.0 or newer
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2018)
  • Pharmacokinetics - Area Under Curve [ Time Frame: On Week 2 prior to first BCG instillation ]
    PK measurement expressed as area under curve for APL-1202
  • Pharmacokinetics - Area Under Curve [ Time Frame: On Week 6 prior to fifth BCG instillation ]
    PK measurement expressed as area under curve for APL-1202
  • Pharmacokinetics - Maximum Plasma Concentration [ Time Frame: On Week 2 prior to first BCG instillation ]
    PK measurement expressed as maximum plasma concentration for APL-1202
  • Pharmacokinetics - Maximum Plasma Concentration [ Time Frame: On Week 6 prior to fifth BCG instillation ]
    PK measurement expressed as maximum plasma concentration for APL-1202
  • Pharmacokinetics - Half-Life [ Time Frame: On Week 2 prior to first BCG instillation ]
    PK measurement expressed as half-life for APL-1202
  • Pharmacokinetics - Half-Life [ Time Frame: On Week 6 prior to fifth BCG instillation ]
    PK measurement expressed as half-life for APL-1202
  • Pharmacokinetics - Cumulative Amount in Urinary Excretion [ Time Frame: Eight hours after first dose on Week 2 prior to first BCG instillation ]
    PK measurement expressed as cumulative amount in urinary excretion for APL-1202
  • Pharmacokinetics - Cumulative Amount in Urinary Excretion [ Time Frame: Eight hours after first dose on Week 6 prior to fifth BCG instillation ]
    PK measurement expressed as cumulative amount in urinary excretion for APL-1202
  • Pharmacokinetics - Cumulative Fraction of Dose in Urinary Excretion [ Time Frame: Eight hours after first dose on Week 2 prior to first BCG instillation ]
    PK measurement expressed as cumulative fraction of dose in urinary excretion for APL-1202
  • Pharmacokinetics - Cumulative Fraction of Dose in Urinary Excretion [ Time Frame: Eight hours after first dose on Week 6 prior to fifth BCG instillation ]
    PK measurement expressed as cumulative fraction of dose in urinary excretion for APL-1202
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of APL-1202 in Non-Muscle Invasive Bladder Cancer Patients Who Are Resistant to One Induction Course of BCG Treatment
Official Title  ICMJE A Phase Ib Study of APL-1202 in NMIBC Patients Who Are Resistant to One Induction Course of BCG Treatment
Brief Summary A Phase Ib, open label, non randomized study to measure the safety and PK characteristics of APL-1202 at steady-state in adult male and female BCG resistant NMIBC patients when it is administered alone and concurrently with BCG.
Detailed Description Six eligible participants will be administered with APL-1202 one week prior to the first BCG instillation, during the six-week course of BCG instillation, and additional five weeks, for a total of 12 weeks of dosing. Safety assessment will be performed during the entire 13 week study duration. Plasma and urine samples will be collected from each participant at prior to first and fifth BCG instillations for PK analysis.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Muscle Invasive Bladder Cancer (NMIBC)
Intervention  ICMJE Drug: APL-1202
To assess the safety and pharmacokinetics of APL-1202 alone and in combination with Bacillus Calmette Guerin
Study Arms  ICMJE Experimental: APL-1202
  • APL-1202 will be administered orally at daily 750 mg (250 mg, TID) for 5-7 days prior to the first intravesical BCG treatment and continue for additional 11 weeks (a total 12 weeks of dosing with APL-1202).
  • Standard intravesical BCG induction course (once weekly for 6 weeks) 50 mg TICE BCG in 50 mL sterile saline (or a full dose standard vial of BCG) will be initiated on Week 2.
Intervention: Drug: APL-1202
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 10, 2018)
6
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 30, 2020
Actual Primary Completion Date October 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Subject Eligibility Criteria:

Inclusion Criteria:

  1. History of Intermediate Risk or High Risk Transitional Cell Carcinoma Non-Muscle Invasive Bladder Cancer as defined by AUA Guidelines:

    AUA Risk Stratification for Non-Muscle Invasive Bladder Cancer

    Low Risk LGa solitary Ta ≤ 3cm PUNLMPb

    Intermediate Risk Recurrence within 1 year Solitary LG Ta > 3cm LG Ta, multifocal HGc Ta, ≤ 3cm LG T1

    High Risk HG T1 Any recurrent, HG Ta HG Ta, >3cm (or multifocal) Any CISd Any BCG failure in HG patient Any variant histology Any LVIe Any HG prostatic urethral

    a. LG = low grade; b. PUNLMP = papillary urothelial neoplasm of low malignant potential; c. HG = high grade; d. CIS=carcinoma in situ; e. LVI = lymphovascular invasion.

  2. History of prior induction course of intravesical BCG, using 1/3 to full dose of BCG for 6 treatments (BCG Naïve will not be eligible). Previous BCG treatment in combination with interferon is allowed.
  3. Patients who are eligible will either receive maintenance course (3 treatments 1/3 to full dose) or repeat induction course (6 treatments 1/3 to full dose)
  4. Principal Investigator's discretion if patients who have a negative cystoscopy or urine cytology following initial BCG induction, can be placed on maintenance BCG to recurrence of bladder cancer
  5. 18 years of age or older
  6. Eastern Cooperative Oncology Group (ECOG) performance status < 2
  7. Not pregnant or lactating
  8. Subjects with child bearing or fathering potential must agree to use adequate contraception during the study and for 3 months after last treatment of investigational drug
  9. Agree to study specific informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
  10. Adequate baseline complete blood count (CBC), renal and hepatic function:

1) Parameters described as WBC > 3000 cells/mm3, ANC > 1,000 cells/mm3, hemoglobin > 8.5 g/dL, and platelet count >100,000 cells/mm3 2) Adequate renal function: serum creatinine < 1.5 x upper limit of normal (ULN) 3) Bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are not more than 2 x Upper Limits of Normal 4) Absolute lymphocyte count ≥ 800/μL before the first dose of APL-1202

Exclusion Criteria:

  1. Stage T2 or above urothelial carcinoma or urothelial carcinoma outside the bladder
  2. Stage T1 NMIBC recurred at 3 months or shorter from the first dose of prior induction BCG course
  3. Recurrent high-grade Ta/T1 disease within 6 months from the last dose of adequate BCG therapy
  4. Previous systemic immunotherapy for bladder cancer
  5. Prior major surgery (not Transurethral Resection of Bladder Tumor [TURBT/Cystoscopy]), radiation therapy, or systemic therapy within 8 weeks of starting the study treatment
  6. National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage within four weeks from the starting study treatment
  7. Any of the following medical conditions within the six months prior to investigational 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
  8. Hypertension that cannot be controlled by medications
  9. Optic nerve disorders or with a history of optic nerve disorders
  10. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational drug administration, or may interfere with the interpretation of study results in the judgment of the Investigator
  11. Clinically meaningful allergic reactions or any known hypersensitivity or prior reaction to any of the formulation components in the investigational drug
  12. Systemic treatment on any investigational clinical trial within 28 days (or 5 half-lives of that agent, whichever is greater) prior to enrollment
  13. Concurrent treatment with immunosuppressive or immunomodulatory agents, including any systemic steroid (exception: inhaled or topically applied steroids, and acute and chronic standard dose nonsteroidal anti-inflammatory drugs (NSAIDs), are permitted). Use of a short course (i.e., ≤ 2 day) of a glucocorticoid is acceptable to prevent a reaction to the IV contrast used for: computed tomography (CT) scans
  14. Immunosuppressive therapy, including: cyclosporine, anti-thymocyte globulin, or tacrolimus within three months of study entry
  15. Concurrent treatment with strong inducers or inhibitors of CYP450 enzymes
  16. Concurrent treatment with low therapeutic index drugs (such as methotrexate) that are renally cleared by OAT1- and OAT3-mediated transport
  17. History of prior malignancy, except for adequately treated in situ cancer or basal cell or squamous cell skin cancer or other cancers (e.g. breast, prostate) for which the patient has been disease free and/or received curative therapy. Exclusion of patients described above will be at the discretion of the Sponsor.
  18. Progressive or persistent viral or bacterial infection
  19. All infections must be resolved, and the subject must remain afebrile for seven days without antibiotics prior to enrollment
  20. Urinary tract infection, including particularly bladder infection, must be resolved prior to being placed on study
  21. Unmanageable active gastric ulcer or inflammation of gastrointestinal (GI) tract
  22. Gastric bleeding within last 6 months prior to enrollment
  23. Anuria
  24. Unable to take oral medication
  25. Unwilling or unable to comply with the protocol or cooperate fully with the Investigator and site personnel
  26. Unwilling to sign the informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03672240
Other Study ID Numbers  ICMJE YHGT-NB-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party AsierisPharma ( Asieris Pharmaceutical Technologies Co., Ltd. )
Study Sponsor  ICMJE Asieris Pharmaceutical Technologies Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Harish Dave, MD Linical Accelovance
PRS Account AsierisPharma
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP