Study of ONCOFID-P-B (PACLITAXEL-HYALURONIC ACID)
Study Details
Study Description
Brief Summary
This is a phase III, single-arm, multicenter, international study to assess the efficacy and safety of ONCOFID-P-B following intravesical instillation in adult patients with histologically and cytologically confirmed CIS, with or without concomitant Ta-T1, who are unresponsive to BCG therapy and unwilling or unfit to undergo radical cystectomy.
After providing written informed consent (in presence of an Independent Witness, if applicable), patients will receive an induction therapy consisting of 12 weekly intravesical instillations of ONCOFID-P-B (induction phase). Patients who achieve a CR by Investigator assessment at the end of the induction phase will enter the maintenance phase and receive monthly treatment for an additional 12 months or until recurrence of CIS/Ta-T1 or progression to MIBC or extravesical disease.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ONCOFID P-B (PACLITAXEL-HYALURONIC ACID)
|
Drug: ONCOFID P-B (PACLITAXEL-HYALURONIC ACID)
Schedule: once a week for 12 consecutive weeks (induction therapy). Patients who achieve a complete response at the end of the induction phase will enter the maintenance phase, during which ONCOFID-P-B is administered once a month for 12 months until recurrence or progression of the disease.
|
Outcome Measures
Primary Outcome Measures
- Centrally assessed Complete Response Rate (CRR) - end of induction phase [CRR will be evaluated at the end of the induction phase, at 12 weeks]
CRR calculated as the proportion of patients achieving a CR after 12 weekly intravesical instillations (end of induction phase). CRR will be based on central assessment of response
Secondary Outcome Measures
- Centrally assessed CRR [CRR will be evaluated at 6, 9, 18 and 24 months after treatment start]
CRR calculated as the proportion of patients achieving a CR at 6, 9, 18 and 24 months after treatment start
- Duration of Response (DoR) [DoR will be evaluated at any time during the study up to 24 months after treatment start]
DoR defined as the time from first documented evidence of CR to time of documented recurrence (CIS or Ta-T1), progression to higher grade (MIBC), to extravesical disease or death
- Duration of Response (DoR) rate [DoR rates will be evaluated at 6, 9, 12, 15, 18, 21 and 24 after treatment start]
DoR rate calculated as the proportion of patients who maintained a CR after 6, 9, 12, 15, 18, 21 and 24 months after treatment start.
- Progression rate [Progression rate will be evaluated at 3, 15 and 24 months after treatment start]
Progression rate calculated as the proportion of patients with muscle invasion or extravesical expansion of the disease at 3, 15 and 24 months after treatment start
- Time to progression [Time to progression will be evaluated at any time during the study up to 24 months after treatment start]
Time to progression defined as time from treatment start to time of documented tumor progression to MIBC or extravesical disease.
- Rate of patients undergoing cystectomy [Rate of patients undergoing cystectomy will be evaluated at 3 months (end of induction phase), 15 and 24 months after treatment start.]
Proportion of patients undergoing cystectomy for disease progression at 3 months (end of induction phase), 15 and 24 months after treatment start.
- event-free survival (EFS) [event-free survival (EFS) will be evaluated at any time during the study up to 24 months after treatment start]
EFS defined as time from treatment start to the time of documented recurrence after CR, or progression or death due to any cause.
- Overall survival (OS) [overall survival (OS) will be evaluated at any time during the study up to 24 months after treatment start]
OS defined as time from treatment start to death due to any cause.
- Incidence of Treatment-Emergent Adverse Events (Overall Safety) [Safety data will be evaluated up to 16 months]
Overall safety and tolerability evaluated throughout the study on the basis of the incidence, nature, severity and causality of TEAEs, coded to preferred term and system organ class (SOC) using the Medical Dictionary for Regulatory Activities (MedDRA) and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5 and the incidence of serious adverse events (SAEs)
- Treatment time of retention (tolerability) [Tolerability will be evaluated up to 16 months]
The tolerability of ONCOFID-P-B expressed as the ability to retain intravesical instillation for the desired dwell time (120 minutes) and measured as time of retention.
Eligibility Criteria
Criteria
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 histologically confirmed CIS of the bladder with or without concomitant Ta-T1 and with no evidence of metastases demonstrated by abdominal CT scan.
-
"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.
-
Complete resection of Ta-T1 papillary lesions before entering the trial in patients with concomitant CIS and papillary tumors (residual CIS acceptable).
-
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 ≥ 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.
-
Female in non-reproductive years (defined as surgically sterile or one year postmenopausal). Female of childbearing potential must agree to practice complete abstinence or agree to use highly effective contraceptive methods, which include:
-
Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject.
-
Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system, or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.
Male patients must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 1 month following the last study drug infusion.
- Able and willing to comply with the scheduled visits, therapy plans, and laboratory tests required in this protocol.
Exclusion Criteria:
-
Current or previous muscle-invasive disease (T2-T4) or metastatic urothelial carcinoma.
-
Suspected hypersensitivity to paclitaxel or to any of the Oncofid-P-B constituents.
-
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.
-
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, or previous intravesical BCG therapy, which can be given at least 5 weeks before the diagnostic biopsy required for study entry.
-
Symptomatic urinary tract infection or bacterial cystitis. Once successfully treated (negative urine culture), patients may enter the study.
-
Major surgery, other than diagnostic, within 4 weeks prior to treatment.
-
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.
-
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 3 months preceding treatment start.
-
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 unwilling to use adequate birth control measures for the duration of the study and until 3 months after the end of treatment.
-
Subjects who have a mean QTc >480 msec at baseline and who need concomitant medications which may cause QT prolongation.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Fidia Farmaceutici s.p.a.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R39_21_01