RECRUITING

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

Conditions

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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 with residual CIS at the end of induction treatment are eligible to enter a re-induction course of therapy (reinduction phase). Patients with stable disease by Investigator assessment defined as neither increased or decreased in extent or severity compared to baseline, are not eligible for re-induction therapy. Patients who achieve a complete resonde (CR) at the end of the induction or re-induction phase enter in the maintenance phase and receive monthly intravesical instillations of ONCOFID-P-B for an additional 12 monsthe or untile recurrence of CIS/HG Ta-T1 or progression to MIBC or extravesical disease. Patients who do not achieve a CR at the end of induction or re-induction phase, will discontinue investigational treatement and are followed up until month 48 from induction or re-induction start, or until a new antitumor therapy is initiated, wichever occurs first. Tumor response is evaluated by cystoscopy, cytology and biopsy at the end of the induction and re-induction phases and at Safety Follow Up Visit (SFUV). During the maintenance/follow-up period, tumorresponse is evaluated by cystoscopy and cytology every 3 months for up to 24 months from induction or re-induction start, and then every 6 months for an additional 2 years (long-term follow-up). Tumor biopsies are performed in case of of positive cystoscopy and/or cytology. Random biopsies are to be performed at 6, 12 and 18 months after the end of the induction or re-induction phase in responding patients (i.e. at 9, 15 and 21 months after induction or re-induction start.

Official 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)

Quick Facts

Study Start:2022-12-29

Study Completion:2027-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05024773

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 histologically confirmed CIS of the bladder with or without concomitant recurrent HG Ta-T1 and with no evidence of metastases demonstrated by abdominal CT scan or MRI. 4. "BCG unresponsive" patients who refuse radical cystectomy or are not clinically suitable for cystectomy. BCG unresponsive disease is defined as persistent or recurrent CIS alone or with recurrent HG Ta-T1 within 12 months of completion of adequate BCG therapy. * 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, obvious areas of CIS should also be fulgurated). 1. In patients with T1 papillary lesions undergoing resection of the base of the lesion, the biopsy should contain muscle fibers. 2. In patients undergoing transurethal resection of their bladder tumors, absence of locally advanced disease should be confirmed by pelvic examination under anesthesia. 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, * 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 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 (\\) 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 laboratory tests required in this protocol.	1. Current or previous muscle-invasive disease (T2-T4) or metastatic urothelial carcinoma. 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 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. 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 are not clinically stable; examples of permitted concurrent recent second malignancies are: adequately treated basal cell or 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/dL, Gleason score 6 or less and cT1. 10. 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). 11. Presence of significant urologic disease interfering with intravesical therapy. 12. 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. 13. Known substance and/or alcohol abuse. 14. 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. 15. Pregnancy, lactating women or women of childbearing potential (WOCBP) unwilling to use adequate birth control measures for the duration of the study and until 3 months after the end of treatment. 16. 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. 17. Subjects who have a mean QTc \>480 msec at baseline and who need concomitant medications which may cause QT prolongation. 18. Persons deprived of liberty by judical or administrative decision, adults subjects 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.

Inclusion Criteria

Exclusion 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 histologically confirmed CIS of the bladder with or without concomitant recurrent HG Ta-T1 and with no evidence of metastases demonstrated by abdominal CT scan or MRI.
4. "BCG unresponsive" patients who refuse radical cystectomy or are not clinically suitable for cystectomy. BCG unresponsive disease is defined as persistent or recurrent CIS alone or with recurrent HG Ta-T1 within 12 months of completion of adequate BCG therapy.
* 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, obvious areas of CIS should also be fulgurated).
1. In patients with T1 papillary lesions undergoing resection of the base of the lesion, the biopsy should contain muscle fibers.
2. In patients undergoing transurethal resection of their bladder tumors, absence of locally advanced disease should be confirmed by pelvic examination under anesthesia.
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,
* 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 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 (\*\*)
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 laboratory tests required in this protocol.

1. Current or previous muscle-invasive disease (T2-T4) or metastatic urothelial carcinoma.
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 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.
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 are not clinically stable; examples of permitted concurrent recent second malignancies are: adequately treated basal cell or 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/dL, Gleason score 6 or less and cT1.
10. 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).
11. Presence of significant urologic disease interfering with intravesical therapy.
12. 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.
13. Known substance and/or alcohol abuse.
14. 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.
15. Pregnancy, lactating women or women of childbearing potential (WOCBP) unwilling to use adequate birth control measures for the duration of the study and until 3 months after the end of treatment.
16. 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.
17. Subjects who have a mean QTc \>480 msec at baseline and who need concomitant medications which may cause QT prolongation.
18. Persons deprived of liberty by judical or administrative decision, adults subjects 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.

Contacts and Locations

Study Contact

Nicola Giordan

CONTACT

+390498232512

ngiordan@fidiapharma.it

Study Locations (Sites)

Banner Health- MD Anderson Cancer Center

Gilbert, Arizona, 85234

United States

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121

United States

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, 21287

United States

University of Minnesota

Minneapolis, Minnesota, 55455

United States

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425

United States

Collaborators and Investigators

Sponsor: Fidia Farmaceutici s.p.a.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-12-29

Study Completion Date2027-11

Study Record Updates

Study Start Date2022-12-29

Study Completion Date2027-11

Terms related to this study

Additional Relevant MeSH Terms

Bladder Carcinoma in Situ (CIS)