Evaluation of Intravesical ONCOFID-P-B (Paclitaxel Obaluronate) in BCG-Unresponsive Carcinoma in Situ of the Bladder with or without Ta-T1 Papillary Disease

Trial ID: 2024-512568-72-00
Protocol: R39_21_01
Sponsor: Fidia Farmaceutici S.p.A.

Trial statistics

science

test molecule

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Bladder cancer stage 0 with cancer in situ

Objectives

The primary objective of this phase III study is to evaluate the **antitumor activity** of ONCOFID-P-B, a paclitaxel-hyaluronic acid conjugate, in patients with BCG-unresponsive Carcinoma in Situ of the bladder, with or without Ta-T1 papillary disease. This is assessed through the centrally evaluated complete response rate (CRR) at any time. The clinical relevance of this objective lies in its potential to provide an effective treatment option for patients who do not respond to standard Bacillus Calmette-Guérin (BCG) therapy, addressing a significant unmet need in bladder cancer management.

Secondary objectives include: - Evaluating the antitumor activity of ONCOFID-P-B using centrally assessed CRR at various time points up to 48 months after induction or re-induction start. - Assessing the duration of response (DoR) and DoR rates at specified intervals. - Evaluating progression rates and time to progression. - Determining the rate of patients undergoing cystectomy and the time to cystectomy. - Assessing event-free survival (EFS) and overall survival (OS).

Participants

The clinical trial involves a total of **15 participants** diagnosed with **BCG-unresponsive Carcinoma in Situ of the bladder**, with or without Ta-T1 papillary disease. The study population includes both male and female subjects aged **18 years or older**. Participants were selected based on their medical condition, specifically those who are BCG-unresponsive and either refuse or are unfit for radical cystectomy. The trial includes individuals with a confirmed histological diagnosis of persistent or recurrent carcinoma in situ, with no evidence of metastases. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2, indicating they are ambulatory and capable of self-care. Adequate organ function is a prerequisite, with specific laboratory values outlined for neutrophil count, platelets, hemoglobin, liver enzymes, and serum creatinine. Lifestyle considerations include the requirement for women of childbearing potential to use highly effective contraceptive methods and for male participants with partners of childbearing potential to use effective contraception. The trial population is considered vulnerable, and all participants must be willing and able to comply with the study's scheduled visits, therapy plans, and laboratory tests.

Plans and Procedures

The clinical trial is a **Phase III** single-arm study designed to evaluate the efficacy and safety of **ONCOFID-P-B**, an **intravesical solution** containing **paclitaxel obaluronate**, in patients with **BCG-unresponsive Carcinoma in Situ of the bladder** with or without Ta-T1 papillary disease. The primary objective is to assess the antitumor activity of the investigational product by measuring the centrally assessed complete response rate (CRR) at any time. The trial is expected to run from February 2023 to May 2030, with the estimated recruitment start date being February 10, 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, histological confirmation of the disease, and adequate organ function. Following the screening, participants will receive the investigational product intravesically, with follow-up visits scheduled to monitor response and safety. These visits will occur at various intervals, including at the end of induction or re-induction therapy, and at 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, and 48 months post-treatment initiation. The end-of-study visit will mark the conclusion of the participant's involvement in the trial.

The expected length of participant involvement is up to 48 months, depending on individual response and disease progression. Conditions that may lead to early termination from the study include disease progression to muscle-invasive bladder cancer (MIBC) or extravesical disease, unacceptable toxicity, or withdrawal of consent. The trial will utilize local assessments to guide treatment decisions, while central assessments will be used for statistical analysis of efficacy endpoints. The study aims to provide comprehensive data on the duration of response, progression rates, and overall survival, contributing valuable insights into the management of this challenging condition.

Treatment

The clinical trial involves the administration of **ONCOFID-P-B**, an experimental medication formulated as an **intravesical solution**. The active substance in ONCOFID-P-B is **paclitaxel obaluronate**, a polymer-based compound. This investigational drug is designed for **intravesical use**, meaning it is directly instilled into the bladder. The maximum daily dose of ONCOFID-P-B is 600 mg, with a total maximum dose of 21.6 g over the course of the treatment. The treatment period is limited to a maximum of 19 weeks. The pharmaceutical form and administration route are specifically chosen to target **Carcinoma in Situ of the bladder**, particularly in patients who are unresponsive to BCG therapy, with or without Ta-T1 papillary disease.

In this study, ONCOFID-P-B is the sole experimental treatment, and no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is structured as a single-arm study, focusing on the efficacy and safety of the investigational drug. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The study aims to evaluate the antitumor activity of ONCOFID-P-B by assessing the complete response rate (CRR) centrally at any time during the trial.

Efficacy

The efficacy of ONCOFID-P-B, an intravesical solution containing **paclitaxel obaluronate**, will be assessed in a Phase III clinical trial involving patients with BCG unresponsive Carcinoma in Situ of the bladder, with or without Ta-T1 papillary disease. The primary endpoint for evaluating efficacy is the complete response rate (CRR), which is calculated as the proportion of patients achieving a complete response (CR) at any time, based on central assessment. Local assessments will guide the decision to initiate the maintenance phase, while the statistical analysis of efficacy endpoints will rely on central assessments.

Secondary endpoints include several measures:

CRR at various timepoints, including end-of-induction treatment (EOIT), end-of-re-induction treatment (EORIT), and at 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, and 48 months post-induction or re-induction start.
Duration of response (DoR), defined as the time from first documented CR to recurrence, progression to muscle-invasive bladder cancer (MIBC), extravesical disease, or death.
DoR rate, progression rate, time to progression, proportion of patients undergoing cystectomy, time to cystectomy, event-free survival (EFS), and overall survival (OS).

These parameters will be measured and analyzed at specified intervals to comprehensively evaluate the antitumor activity of the treatment.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Willing and able to freely provide written informed consent (in presence of an Independent Witness if applicable) prior to performing study procedures.
Age 18 years or older, male or female.
Persistent or recurrent CIS of the bladder histologically confirmed, with or without concomitant recurrent HG Ta-T1 and with no evidence of metastases demonstrated by abdominal CT scan or MRI.
BCG unresponsive patients who refuse or are unfit for radical cystectomy. BCG-unresponsive disease is defined as persistent or recurrent CIS alone or with recurrent HG Ta-T1 disease within 12 months of completion of adequate BCG therapy. Adequate BCG therapy is defined as at least one of the following: 1) At least five full doses of six doses of an initial induction course plus at least two full doses of three doses of maintenance therapy. 2) At least five full doses of six doses of an initial induction course plus at least two full doses of six doses of a second induction course.
Complete resection of Ta-T1 papillary lesions before entering the trial in patients with concomitant CIS and papillary tumors (residual CIS acceptable, obvious areas of CIS should also be fulgurated). a. In patients with T1 papillary lesions undergoing resection of the base of the lesion, the biopsy should contain muscle fibers. b. In patients undergoing transurethral resection of their bladder tumors, absence of locally advanced disease should be confirmed by pelvic examination under anesthesia.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
Adequate organ function: absolute neutrophil count ≥ 1,500/mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 8.5 g/dL, ALT/AST ≤ 1.5 x upper limit of normal (ULN), alkaline phosphatase ≤ 5 x ULN, total serum bilirubin ≤ 1.5 x ULN, for patients with Gilbert’s Syndrome ≤ 3 x ULN, serum creatinine ≤ 2.2 mg/dL.
Women in non-reproductive years (defined as surgically sterile or one year postmenopausal). Women of childbearing potential (WOCBP*) must have a negative serum pregnancy test upon entry into this study and agree to use highly effective contraceptive methods, i.e. methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: − oral − intravaginal − transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation: − oral − injectable − implantable • intrauterine device (IUD) • intrauterine hormone-releasing system ( IUS) • bilateral tubal occlusion • vasectomised partner (**) • sexual abstinence (***) (*) Women of childbearing potential (WOCBP): fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, confirmation with more than one FSH measurement is required. (**) Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success. (***) Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated to the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
Male patients with WOCBP partners must agree to use effective contraceptive methods, i.e.: • condom • consider contraception for non-pregnant WOCBP partner.
Able and willing to comply with the scheduled visits, therapy plans, and laboratory tests required in this protocol.

cancel

Exclusion Criteria

Current or previous muscle-invasive disease (T2-T4) or metastatic urothelial carcinoma.
Subjects who, in the opinion of the Investigator, cannot tolerate intravesical administration or intravesical surgical manipulation (cystoscopy, biopsy) due to the presence of serious comorbid condition(s) (e.g., uncontrolled cardiac or respiratory disorders).
Presence of significant urologic disease interfering with intravesical therapy.
Current enrollment or participation in another therapeutic clinical trial within 6 months preceding screening. Patients previously included in a BCG-only study arm might be enrolled following discussion with the medical monitor and/or sponsor if the definition of adequate BCG therapy is met.
Known substance and/or alcohol abuse.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry in this study or could compromise protocol objectives.
Pregnancy, lactating women or women of childbearing potential (WOCBP) unwilling to use adequate birth control measures for the duration of the study and until 6 months after the end of treatment.
Male patients with WOCBP partners unwilling to use contraceptive methods for the duration of the study and until 6 months after the end of treatment.
Subjects who have a mean QTc >450 msec for males and >470 msec for females at baseline and who need concomitant medications which may cause QT prolongation.
Patient with more than 12 months between inclusion (week 1) and the last BCG instillation.
Suspected hypersensitivity to paclitaxel or to any of the ONCOFID-P-B constituents.
Previous or concomitant urothelial carcinoma of the upper urinary tract or the prostatic urethra. Freedom from upper tract disease must be demonstrated by intravenous pyelogram, retrograde pyelogram, CT scan or MRI.
Current or prior systemic therapy for bladder cancer.
Intravesical therapy within 4 weeks prior to beginning study treatment with the exception of cytotoxic agents (e.g. mitomycin C, doxorubicin and epirubicin) when administered as a single instillation immediately following a TURBT procedure between 14 to 60 days prior to beginning study treatment.
Symptomatic urinary tract infection or bacterial cystitis.
Major surgery, other than diagnostic, within 4 weeks prior to treatment.
Patients who have previous or concurrent malignancies that require treatment and are not clinically stable; examples of permitted concurrent recent second malignancies are: adequately treated basal cell, squamous cell skin cancer, in situ carcinoma of the cervix or prostate cancer on active surveillance at low risk for progression, defined as prostate-specific antigen (PSA) <10 ng/mL, Gleason score 6 or less and cT1.
Applies to France only: Persons deprived of liberty by judicial or administrative decisions, adults subject to a legal protection measure (under guardianship/curators), persons under protective measures and persons not affiliated with social security will be excluded from the study.