Study of Vicinium for Treating Patients With Non-Invasive Urothelial Carcinoma In Situ

• Sponsor: Viventia Bio (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00462488
• Collaborator: (none)
• Enrollment: 46
• Locations: 21
• Arms: 2
• Duration (Months): 31
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and tolerability of Vicinium when administered as a monotherapy intravesical instillation in patients with non-invasive urothelial carcinoma in situ (CIS) who failed previous treatment with Bacille Calmette Guérin (BCG).

Condition or Disease	Intervention/Treatment	Phase
Urinary Bladder Cancer; Bladder Cancer; Bladder Neoplasms; Bladder Tumors	Drug: Vicinium	Phase 2

Detailed Description

A phase II study was performed to assess the efficacy and tolerability of intravesical Vicinium in patients with urothelial carcinoma in situ of the bladder. Bacillus Calmette-Guérin treatment had previously failed in all patients. A total of 46 patients were treated with Vicinium with half being administered 30mg/dose once per week for 6 weeks (cohort 1) and the other half (cohort 2) the same dose but administered once per week for 12 consecutive weeks. Disease assessments consisting of urine cytology, cystoscopy and, if indicated, biopsy were performed at 3 month intervals. Patients that were disease-free at the assessment time point were allowed to continue treatment in the maintenance phase which consisted of three weekly doses, followed by 9 weeks of no treatment. As long as the patient remained disease-free, treatment continued for a total of one year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Patients With Non-Invasive Urothelial Carcinoma in Situ (CIS) Previously Treated With Bacille Calmette-Guérin (BCG)
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment Schedule A - Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 6 weeks. If free of disease at 12 weeks after the first instillation, the subject enters Maintenance dosing in which 30 mg of Vicinium is administered once per week for 3 weeks followed by 9 weeks of no therapy. If the subject had histologically confirmed disease that is stage <T2, they repeat the Induction phase dosing. If the subject is free of disease, the subject enters the maintenance dosing phase of every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 51 (end-of-study [EOS]).	Drug: Vicinium; Intravesical administration of Vicinium; Other Names: VB4-845
Active Comparator: Treatment Schedule B Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 12 weeks followed by 1 week of no therapy. If 13 weeks after the first instillation of Vicinium the subject is free of disease, they have a break from therapy before entering Maintenance dosing in which 30 mg of Vicinium is administered once weekly for 3 weeks followed by 9 weeks of no therapy. If the subject is free of disease, additional maintenance cycle(s) are repeated every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 57 (EOS).	Drug: Vicinium; Intravesical administration of Vicinium; Other Names: VB4-845

Outcome Measures

Primary Outcome Measures

1. Treatment Schedule A: 12-Week Efficacy, Treatment Schedule B: 13-Week Efficacy [12 or 13 weeks]

   Complete response rate in subjects with carcinoma in situ (CIS) non-muscle invasive bladder cancer (NMIBC) following the induction phase (3-month evaluation point) of Vicinium treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Disease Characteristics

• The patient must be male or female 18 years of age or older.

• The patient must have histologically-confirmed Transitional Cell Carcinoma (TCC) of the bladder.

• The patient must have histologically-confirmed carcinoma in situ (CIS), with or without non-invasive papillary disease

• The patient must have immunohistochemically-confirmed EpCAM positive disease.

• The patient must have a life expectancy of at least 12 months.

Prior/Concurrent Therapy

• The patient must have, within the last 24 months, failed to respond to at least 1 cycle of treatment with BCG (with or without interferon) or be intolerant to BCG treatment.

• The patient must have had a transurethral resection of the bladder tumour (TURBT) mapping the location of tumour and quantifying the area of bladder affected.

• The patient must have documented residual CIS (i.e. unresectable disease) prior to study drug administration.

Patient Characteristics

The patient must have adequate organ function, as defined by the clinical trial protocol

Other

• The patient must have the ability to understand and sign an Independent Ethics Committee or Institutional Review Board (IEC/IRB)- approved informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment and is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

• The patient has evidence of urethral or upper tract transitional cell carcinoma (TCC) by biopsy or upper tract radiological imaging (i.e. intravenous pyelogram, computed tomography (CT) urogram, or retrograde pyelogram) within the past 2 years

• The patient has hydronephrosis

• The patient has had prior intravesical chemotherapy or investigational or anti-cancer treatments within the last 2 months, inclusive of single-dose adjuvant intravesical chemotherapy immediately post-TURBT

• The patient has existing severe urinary tract infection or recurrent severe bacterial cystitis

• The patient has active, uncontrolled impairment of the renal, hepatobiliary, cardiovascular, gastrointestinal, urogenital, neurologic or hematopoietic systems which, in the opinion of the investigator, would predispose the patient to the development of complications from the administration of intravesical therapy and/or general anesthesia

• Any patient who, in the opinion of the investigator, cannot tolerate intravesical administration or intravesical surgical manipulation (cystoscopy, biopsy) due to the presence of concomitant serious illness (i.e. uncontrolled cardiac or respiratory disorders)

• The patient is pregnant or breast feeding

• Women of reproductive age (who are not either medically or surgically incapable or bearing children) and all men may not participate unless agreeing to use double barrier contraception, or commit to abstinence during the period of therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southeastern Research Group, Inc.	Tallahassee	Florida	United States	32308
2	Johns Hopkins Medical Institutions	Baltimore	Maryland	United States	21287
3	Lawrenceville Urology	Lawrenceville	New Jersey	United States	08648
4	Duke University Medical Center	Durham	North Carolina	United States	27710
5	Oregon Urology Institute Research	Springfield	Oregon	United States	97477
6	Grand Strand Urology	Myrtle Beach	South Carolina	United States	29572
7	Corpus Christi Urology Group, LLP	Corpus Christi	Texas	United States	78404
8	Urology of Virginia	Newport News	Virginia	United States	23606
9	Andreou Research	Surrey	British Columbia	Canada	V3V 1N1
10	Can-Med Clinical Research Inc.	Victoria	British Columbia	Canada	V8T 5G9
11	The Male/Female Health and Research Centre, Royal Court Medical Centre	Barrie	Ontario	Canada	L4M 7G1
12	Urology Resource Centre	Burlington	Ontario	Canada	L7S 1V2
13	McMaster University, Institute of Urology at Saint Joseph's Hospital	Hamilton	Ontario	Canada	L8N 4A6
14	Centre for Applied Urological Research	Kingston	Ontario	Canada	K7L 2V7
15	London Health Sciences Centre	London	Ontario	Canada	N6A 4G5
16	The Fe/Male Health Centre	Oakville	Ontario	Canada	L6H 3P1
17	Todd Webster, M.D.	Owen Sound	Ontario	Canada	N4K 2J1
18	The Scarborough Hospital	Scarborough	Ontario	Canada	M1P 2T7
19	University of Toronto, Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
20	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
21	Centre Hospitalier Universitaire de Sherbrooke, Hopital Fleuimont	Sherbrooke	Quebec	Canada	J1H 5N4

Sponsors and Collaborators

• Viventia Bio

Investigators

• Study Director: Wendy Chapman, Viventia Bio

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Viventia Bio
• ClinicalTrials.gov Identifier: NCT00462488
• Other Study ID Numbers: VB4-845-02-IIA
• First Posted: Apr 19, 2007
• Last Update Posted: May 12, 2020
• Last Verified: Apr 1, 2020

• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Carcinoma in Situ

Study Results

Participant Flow

Arm/Group Title	Treatment Schedule A -	Treatment Schedule B
Arm/Group Description	Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 6 weeks. If free of disease at 12 weeks after the first instillation, the subject enters Maintenance dosing in which 30 mg of Vicinium is administered once per week for 3 weeks followed by 9 weeks of no therapy. If the subject had histologically confirmed disease that is stage <T2, they repeat the Induction phase dosing. If the subject is free of disease, the subject enters the maintenance dosing phase of every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 51 (end-of-study [EOS]). Vicinium: Intravesical administration of Vicinium	Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 12 weeks followed by 1 week of no therapy. If 13 weeks after the first instillation of Vicinium the subject is free of disease, they have a break from therapy before entering Maintenance dosing in which 30 mg of Vicinium is administered once weekly for 3 weeks followed by 9 weeks of no therapy. If the subject is free of disease, additional maintenance cycle(s) are repeated every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 57 (EOS). Vicinium: Intravesical administration of Vicinium
Period Title: Overall Study
STARTED	23	23
Completed Induction Phase	22	23
Completed Induction 2/Maintenance 1	18	9
Completed Maintenance 2	7	6
COMPLETED	3	6
NOT COMPLETED	20	17

Baseline Characteristics

Arm/Group Title	Treatment Schedule A -	Treatment Schedule B	Total
Arm/Group Description	Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 6 weeks. If free of disease at 12 weeks after the first instillation, the subject enters Maintenance dosing in which 30 mg of Vicinium is administered once per week for 3 weeks followed by 9 weeks of no therapy. If the subject had histologically confirmed disease that is stage <T2, they repeat the Induction phase dosing. If the subject is free of disease, the subject enters the maintenance dosing phase of every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 51 (end-of-study [EOS]). Vicinium: Intravesical administration of Vicinium	Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 12 weeks followed by 1 week of no therapy. If 13 weeks after the first instillation of Vicinium the subject is free of disease, they have a break from therapy before entering Maintenance dosing in which 30 mg of Vicinium is administered once weekly for 3 weeks followed by 9 weeks of no therapy. If the subject is free of disease, additional maintenance cycle(s) are repeated every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 57 (EOS). Vicinium: Intravesical administration of Vicinium	Total of all reporting groups
Overall Participants	23	23	46
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 21.7%	4 17.4%	9 19.6%
>=65 years	18 78.3%	19 82.6%	37 80.4%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	71.6	71.5	71.6
Sex: Female, Male (Count of Participants)
Female	6 26.1%	4 17.4%	10 21.7%
Male	17 73.9%	19 82.6%	36 78.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 4.3%	1 2.2%
White	22 95.7%	22 95.7%	44 95.7%
More than one race	1 4.3%	0 0%	1 2.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	15 65.2%	15 65.2%	30 65.2%
United States	8 34.8%	8 34.8%	16 34.8%

Outcome Measures

1. Primary Outcome

Title	Treatment Schedule A: 12-Week Efficacy, Treatment Schedule B: 13-Week Efficacy
Description	Complete response rate in subjects with carcinoma in situ (CIS) non-muscle invasive bladder cancer (NMIBC) following the induction phase (3-month evaluation point) of Vicinium treatment
Time Frame	12 or 13 weeks

Outcome Measure Data

Analysis Population Description

One subject in Treatment Schedule A was not evaluated for complete response after the induction phase as they were ineligible to be on trial and therefore discontinued after receiving one dose of study drug.

Arm/Group Title	Treatment Schedule A -	Treatment Schedule B
Arm/Group Description	Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 6 weeks. If free of disease at 12 weeks after the first instillation, the subject enters Maintenance dosing in which 30 mg of Vicinium is administered once per week for 3 weeks followed by 9 weeks of no therapy. If the subject had histologically confirmed disease that is stage <T2, they repeat the Induction phase dosing. If the subject is free of disease, the subject enters the maintenance dosing phase of every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 51 (end-of-study [EOS]). Vicinium: Intravesical administration of Vicinium	Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 12 weeks followed by 1 week of no therapy. If 13 weeks after the first instillation of Vicinium the subject is free of disease, they have a break from therapy before entering Maintenance dosing in which 30 mg of Vicinium is administered once weekly for 3 weeks followed by 9 weeks of no therapy. If the subject is free of disease, additional maintenance cycle(s) are repeated every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 57 (EOS). Vicinium: Intravesical administration of Vicinium
Measure Participants	22	23
Number (95% Confidence Interval) [percentage of patients]	40.9	39.1

Adverse Events

Time Frame	60 weeks
Arm/Group Title	Treatment Schedule A -		Treatment Schedule B
Arm/Group Description	Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 6 weeks. If free of disease at 12 weeks after the first instillation, the subject enters Maintenance dosing in which 30 mg of Vicinium is administered once per week for 3 weeks followed by 9 weeks of no therapy. If the subject had histologically confirmed disease that is stage <T2, they repeat the Induction phase dosing. If the subject is free of disease, the subject enters the maintenance dosing phase of every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 51 (end-of-study [EOS]). Vicinium: Intravesical administration of Vicinium		Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 12 weeks followed by 1 week of no therapy. If 13 weeks after the first instillation of Vicinium the subject is free of disease, they have a break from therapy before entering Maintenance dosing in which 30 mg of Vicinium is administered once weekly for 3 weeks followed by 9 weeks of no therapy. If the subject is free of disease, additional maintenance cycle(s) are repeated every 12 weeks (3 weeks of therapy followed by 9 weeks of no therapy until disease recurrence is confirmed by positive biopsy or up to a maximum of Week 57 (EOS). Vicinium: Intravesical administration of Vicinium
All Cause Mortality
	Treatment Schedule A -		Treatment Schedule B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)
Serious Adverse Events
	Treatment Schedule A -		Treatment Schedule B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/23 (4.3%)		5/23 (21.7%)
Injury, poisoning and procedural complications
Post procedural hemorrhage	0/23 (0%)	0	1/23 (4.3%)	1
Hip Fracture	0/23 (0%)	0	1/23 (4.3%)	1
Renal and urinary disorders
urinary retention	1/23 (4.3%)	1	0/23 (0%)	0
Extravasation during TURBT	0/23 (0%)	0	1/23 (4.3%)	1
Vascular disorders
Deep Vein Thrombosis	0/23 (0%)	0	1/23 (4.3%)	1
Hypotension	0/23 (0%)	0	1/23 (4.3%)	1
Other (Not Including Serious) Adverse Events
	Treatment Schedule A -		Treatment Schedule B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/23 (91.3%)		22/23 (95.7%)
Gastrointestinal disorders
Diarrhoea	1/23 (4.3%)	1	3/23 (13%)	3
Vomiting	1/23 (4.3%)	1	2/23 (8.7%)	2
General disorders
Fatigue	5/23 (21.7%)	12	5/23 (21.7%)	5
Influenza like illness	4/23 (17.4%)	4	2/23 (8.7%)	4
Localized Oedema	0/23 (0%)	0	3/23 (13%)	4
Pyrexia	3/23 (13%)	4	2/23 (8.7%)	2
Infections and infestations
Nasopharyngitis	2/23 (8.7%)	2	2/23 (8.7%)	2
Urinary tract infection	3/23 (13%)	4	6/23 (26.1%)	11
Investigations
Blood urine present	2/23 (8.7%)	2	3/23 (13%)	5
Cells in urine	2/23 (8.7%)	2	1/23 (4.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/23 (8.7%)	2	4/23 (17.4%)	10
Nervous system disorders
Dizziness	3/23 (13%)	4	2/23 (8.7%)	2
Renal and urinary disorders
Bladder pain	3/23 (13%)	5	2/23 (8.7%)	3
Dysuria	11/23 (47.8%)	18	17/23 (73.9%)	53
Haematuria	8/23 (34.8%)	16	5/23 (21.7%)	9
Haemorrhage urinary tract	2/23 (8.7%)	2	1/23 (4.3%)	4
Micturition urgency	3/23 (13%)	4	7/23 (30.4%)	8
Nocturia	2/23 (8.7%)	2	5/23 (21.7%)	8
Pollakiuria	3/23 (13%)	3	8/23 (34.8%)	10
Urinary incontinence	1/23 (4.3%)	1	3/23 (13%)	3
Vascular disorders
Hypertension	3/23 (13%)	3	1/23 (4.3%)	1
Hypotension	3/23 (13%)	3	0/23 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.