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

Non-Muscle Invasive Bladder Cancer (NMIBC) Clinical Trial

— NMIBC  

Official title:

A Phase Ib Study of APL-1202 in NMIBC Patients Who Are Resistant to One Induction Course of BCG Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03672240
• Other study ID #: YHGT-NB-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 30, 2018
• Est. completion date: June 30, 2020

Study information

• Verified date: July 2020
• Source: AsierisPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: June 30, 2020
• Est. primary completion date: October 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Non-Muscle Invasive Bladder Cancer (NMIBC)
• Urinary Bladder Neoplasms

Intervention

Drug:
• APL-1202
To assess the safety and pharmacokinetics of APL-1202 alone and in combination with Bacillus Calmette Guerin

Locations

Country	Name	City	State
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	The Icahn School of Medicine at Mt. Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Asieris Pharmaceutical Technologies Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and Severity of Treatment-Related Adverse Events	Incidence and Severity of Treatment-Related Adverse Events as Assessed by CTCAE v.5.0 or newer	13 weeks
Secondary	Pharmacokinetics - Area Under Curve	PK measurement expressed as area under curve for APL-1202	On Week 2 prior to first BCG instillation
Secondary	Pharmacokinetics - Area Under Curve	PK measurement expressed as area under curve for APL-1202	On Week 6 prior to fifth BCG instillation
Secondary	Pharmacokinetics - Maximum Plasma Concentration	PK measurement expressed as maximum plasma concentration for APL-1202	On Week 2 prior to first BCG instillation
Secondary	Pharmacokinetics - Maximum Plasma Concentration	PK measurement expressed as maximum plasma concentration for APL-1202	On Week 6 prior to fifth BCG instillation
Secondary	Pharmacokinetics - Half-Life	PK measurement expressed as half-life for APL-1202	On Week 2 prior to first BCG instillation
Secondary	Pharmacokinetics - Half-Life	PK measurement expressed as half-life for APL-1202	On Week 6 prior to fifth BCG instillation
Secondary	Pharmacokinetics - Cumulative Amount in Urinary Excretion	PK measurement expressed as cumulative amount in urinary excretion for APL-1202	Eight hours after first dose on Week 2 prior to first BCG instillation
Secondary	Pharmacokinetics - Cumulative Amount in Urinary Excretion	PK measurement expressed as cumulative amount in urinary excretion for APL-1202	Eight hours after first dose on Week 6 prior to fifth BCG instillation
Secondary	Pharmacokinetics - Cumulative Fraction of Dose in Urinary Excretion	PK measurement expressed as cumulative fraction of dose in urinary excretion for APL-1202	Eight hours after first dose on Week 2 prior to first BCG instillation
Secondary	Pharmacokinetics - Cumulative Fraction of Dose in Urinary Excretion	PK measurement expressed as cumulative fraction of dose in urinary excretion for APL-1202	Eight hours after first dose on Week 6 prior to fifth BCG instillation