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

NCT03672240 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: YHGT-NB-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

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.

Conditions

Non-Muscle Invasive Bladder Cancer (NMIBC)

Keywords

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Cancer (NMIBC); Oral Antineoplastic Agent

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Pharmacokinetics - Area Under Curve

  On Week 2 prior to first BCG instillation

• Pharmacokinetics - Area Under Curve

  On Week 6 prior to fifth BCG instillation

• Pharmacokinetics - Maximum Plasma Concentration

  On Week 2 prior to first BCG instillation

• Pharmacokinetics - Maximum Plasma Concentration

  On Week 6 prior to fifth BCG instillation

• Pharmacokinetics - Half-Life

  On Week 2 prior to first BCG instillation

Study Arms (1)

APL-1202

EXPERIMENTAL

* 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.

Drug: APL-1202

Interventions

APL-1202 DRUG

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

APL-1202

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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)
• 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
• years of age or older
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Not pregnant or lactating
• 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
• Agree to study specific informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
• Adequate baseline complete blood count (CBC), renal and hepatic function:

You may not qualify if:

• Stage T2 or above urothelial carcinoma or urothelial carcinoma outside the bladder
• Stage T1 NMIBC recurred at 3 months or shorter from the first dose of prior induction BCG course
• Recurrent high-grade Ta/T1 disease within 6 months from the last dose of adequate BCG therapy
• Previous systemic immunotherapy for bladder cancer
• Prior major surgery (not Transurethral Resection of Bladder Tumor \[TURBT/Cystoscopy\]), radiation therapy, or systemic therapy within 8 weeks of starting the study treatment
• National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage within four weeks from the starting study treatment
• 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
• Hypertension that cannot be controlled by medications
• Optic nerve disorders or with a history of optic nerve disorders
• 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
• Clinically meaningful allergic reactions or any known hypersensitivity or prior reaction to any of the formulation components in the investigational drug
• Systemic treatment on any investigational clinical trial within 28 days (or 5 half-lives of that agent, whichever is greater) prior to enrollment
• 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
• Immunosuppressive therapy, including: cyclosporine, anti-thymocyte globulin, or tacrolimus within three months of study entry
• Concurrent treatment with strong inducers or inhibitors of CYP450 enzymes

Sponsors & Collaborators

• Asieris Pharmaceutical Technologies Co., Ltd.: lead

Study Sites (2)

The Icahn School of Medicine at Mt. Sinai

New York, New York, 10029, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Harish Dave, MD

  Linical Accelovance

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2018
• First Posted: September 14, 2018
• Study Start: November 30, 2018
• Primary Completion: October 30, 2019
• Study Completion: June 30, 2020
• Last Updated: July 20, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)