Study of ONCOFID-P-B (PACLITAXEL-HYALURONIC ACID)

Inclusion Criteria:

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

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

3. Persistent or recurrent histologically confirmed CIS of the bladder with or withoutconcomitant recurrent HG Ta-T1 and with no evidence of metastases demonstrated byabdominal CT scan or MRI.

4. "BCG unresponsive" patients who refuse radical cystectomy or are not clinicallysuitable for cystectomy. BCG unresponsive disease is defined as persistent orrecurrent CIS alone or with recurrent HG Ta-T1 within 12 months of completion ofadequate BCG therapy. 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 ofthree doses of maintenance therapy.

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

5. Complete resection of Ta-T1 papillary lesions before entering the trial in patientswith concomitant CIS and papillary tumors (residual CIS acceptable, obvious areas ofCIS should also be fulgurated).

6. In patients with T1 papillary lesions undergoing resection of the base of thelesion, the biopsy should contain muscle fibers.

7. In patients undergoing transurethal resection of their bladder tumors, absenceof locally advanced disease should be confirmed by pelvic examination underanesthesia.

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

9. 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 ≤ 3 X ULN,

• serum creatinine ≤ 2.2 mg/dL.

8. Women in non-reproductive years (defined as surgically sterile or one yearpostmenopausal). Women of childbearing potential (WOCBP) must have a negative serumpregnancy test upon entry into this study and agree to use highly effectivecontraceptive 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 contraceptionassociated with inhibition of ovulation:

• oral

• intravaginal

• transdermal

• progestogen-only hormonal contraception associated with inhibition ofovulation:

• oral

• injectable

• implantable

• intrauterine device (IUD)

• intrauterine hormone-releasing system (IUS)

• bilateral tubal occlusion

• vasectomised partner (*)

• sexual abstinence (**)

9. Male patients with WOCBP partners must agree to use effective contraceptive methods,i.e.:

• condom;

• consider contraception for non-pregnant WOCBP partner.

10. Able and willing to comply with the scheduled visits, therapy plans, and laboratorytests 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 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.

Exclusion Criteria:

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

2. Patients with more than 12 months between inclusion and the last BCG instillation

3. Suspected hypersensitivity to paclitaxel or to any of the Oncofid-P-B constituents.

4. 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.

5. Current or prior systemic therapy for bladder cancer.

6. Intravesical therapy within 4 weeks prior to beginning study treatment with theexception of cytotoxic agents (e.g. mitomycin C, doxorubicin and epirubicin) whenadministered as a single instillation immediately following a TURBT procedurebetween 14 to 60 days prior to beginning study treatment.

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

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

9. Patients who have previous or concurrent malignancies that require treatment and arenot clinically stable; examples of permitted concurrent recent second malignanciesare: adequately treated basal cell or squamous cell skin cancer, in situ carcinomaof the cervix or prostate cancer on active surveillance at low risk for progression,defined as prostate-specific antigen (PSA) <10 ng/dL, Gleason score 6 or less andcT1.

10. Subjects who, in the opinion of the Investigator, cannot tolerate intravesicaladministration or intravesical surgical manipulation (cystoscopy, biopsy) due to thepresence of serious comorbid condition(s) (e.g., uncontrolled cardiac or respiratorydisorders).

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

12. Current enrollment or participation in another therapeutic clinical trial within 6months preceding screening. Patients previously included in a BCG-only study armmight be enrolled following discussion with the medical monitor and/or sponsor ifthe definition of adequate BCG therapy is met.

13. Known substance and/or alcohol abuse.

14. Other severe acute or chronic medical or psychiatric condition or laboratoryabnormality that may increase the risk associated with study participation or mayinterfere with the interpretation of study results and, in the judgment of theInvestigator, would make the patient inappropriate for entry in this study or couldcompromise protocol objectives.

15. Pregnancy, lactating women or women of childbearing potential (WOCBP) unwilling touse adequate birth control measures for the duration of the study and until 3 monthsafter the end of treatment.

16. Male patients with WOCBP partners unwilling to use contraceptive methods for theduration of the study and until 6 months after the end of treatment.

17. Subjects who have a mean QTc >480 msec at baseline and who need concomitantmedications which may cause QT prolongation. Applies to France Only:

18. Persons deprived of liberty by judical or administrative decision, adults subjectsto a legal protection measure (under guardianship/curators), persons underprotective measures and persons not affiliated with social security will be excludedfrom the study.