ORION-BC

Trial Info

Status: Open

Specialty: Bladder

Date Opened: 17/07/2025

Planned Close Date: 31/12/2025

Sponsor: FIDIA Farmaceutici S.p.

Principal Investigator: Mr Michal Smolski

Study Title: A phase III, single-arm study to evaluate the efficacy and safety of ONCOFID-P-B (paclitaxel-hyaluronic acid conjugate) administered intravesically to patients with BCG-unresponsive Carcinoma in Situ of the bladder with or without Ta-T1 papillary disease. Orion-BC Study.

Trial Description

A phase III, single-arm study to evaluate the efficacy and safety of ONCOFID-P-B (paclitaxel-hyaluronic acid conjugate) administered intravesically to patients with BCG-unresponsive Carcinoma in Situ of the bladder with or without Ta-T1 papillary disease

Inclusion Criteria

1. Willing and able to freely provide written informed consent (in presence of an Independent Witness if applicable) prior to performing study procedures.

2. Age 18 years or older, male or female.

3. Persistent or recurrent CIS of the bladder histologically confirmed, with or without concomitant Ta-T1 and with no evidence of metastases demonstrated by abdominal CT scan.

4. "BCG unresponsive" patients who refuse radical cystectomy or are not clinically suitable for cystectomy. BCG unresponsive disease includes BCG refractory (persistent high-grade disease at 6 months despite adequate BCG treatment) and BCG relapsing (recurrence of high-grade disease after achieving a disease-free state at 6 months after adequate BCG).

Patients can be within 6 to 9 months of the last BCG exposure, thereby allowing a 3-month lead time for referral.

Adequate BCG therapy is defined as at least one of the following:

· At least five of six doses of an initial induction course plus at least two of three doses of maintenance therapy.

· At least five of six doses of an initial induction course plus at least two of six doses of a second induction course.

5. Complete resection of Ta-T1 papillary lesions before entering the trial in patients with concomitant CIS and papillary tumors (residual CIS acceptable).

a. In patients with T1 papillary lesions undergoing resection of the base of the lesion, the biopsy should contain muscle fibres.

b. In patients with high-risk disease undergoing transurethral resection of their bladder tumors, absence of locally advanced disease confirmed by pelvic examination under anaesthesia.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

7. Adequate organ function: absolute neutrophil count ≥ 1,500/mm3, platelets ≥ 100,000/mm3, haemoglobin ≥ 10.0 g/dL, ALT/AST ≤ 5 x upper limit of normal (ULN), alkaline phosphatase ≤ 5 x ULN, total serum bilirubin ≤ 1.5 x ULN, serum creatinine ≤ 2.2 mg/dL.

8. Women in non-reproductive years (defined as surgically sterile or one year postmenopausal). Women of childbearing potential (WOCBP) must 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 (**)

Male patients with WOCBP partners do not need contraception measures.

9. Able and willing to comply with the scheduled visits, therapy plans, and laboratory tests required in this protocol.

(*) 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.

Exclusion Criteria

1. Current or previous muscle-invasive disease (T2-T4) or metastatic urothelial carcinoma.

2. Suspected hypersensitivity to paclitaxel or to any of the ONCOFID-P-B constituents.

3. Previous or concomitant cancer 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.

4. Current or prior systemic therapy for bladder cancer.

5. 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, or previous intravesical BCG therapy, which can be given at least 5 weeks before the diagnostic biopsy required for study entry.

6. Symptomatic urinary tract infection or bacterial cystitis. Once successfully treated (negative urine culture), patients may enter the study.

7. Major surgery, other than diagnostic, within 4 weeks prior to treatment.

8. Previous (within the last 5 years) or current malignancies at other sites, except for adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri.

9. 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).

10. Presence of significant urologic disease interfering with intravesical therapy.

11. Current enrollment or participation in another therapeutic clinical trial within 3 months preceding treatment start.

12. Known substance and/or alcohol abuse.

13. 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.

14. Pregnancy, lactating women or women of childbearing potential unwilling to use adequate birth control measures for the duration of the study and until 3 months after the end of treatment.

15. Subjects who have a mean QTc > 480 msec at baseline and who need concomitant medications which may cause QT prolongation.

Contacts

Research Nurse: Amanda Cook (x4656) Amanda.Cook@lthtr.nhs.uk

Administrator: Yecora Lecanda-Swarbrick (x3766)

Link to EDGE

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