Vicinium Treatment for Subjects With Non-muscle Invasive Bladder Cancer Previously Treated With BCG

NCT02449239 | Completed Phase 3 Results DMC

• 1 other identifier: VB4-845-02-IIIA
• Study Type: interventional
• Target: 133
• Locations: 2 countries
• Sites: 70

Brief Summary

Because of the high risk for development of muscle invasive disease, cystectomy is recommended for CIS, high-grade Ta and T1 patients who experience disease recurrence following intravesical therapy. Vicinium is an experimental agent that may provide an alternative to cystectomy

Conditions

Bladder Cancer

Keywords

Urinary Bladder Cancer; Non-muscle invasive bladder cancer; Bladder Neoplasm; Bladder Tumor; CIS; Papillary bladder cancer; High grade bladder cancer

Outcome Measures

Primary Outcomes (2)

• Complete Response Rate at 3 Months

  Complete response rate at 3 months in patients with CIS with or without resected papillary disease following initiation of Vicinium therapy. This is the percentage of patients who were free of high-grade disease at the post-induction (3 month) assessment timepoint. A patient was considered to have a complete response if the urine cytology was reported as negative or atypical AND the cystoscopy was reported as normal or any suspicious areas were deemed negative for high-grade disease upon biopsy assessment.

  3 months from start of treatment

• Duration of Complete Response

  Duration of complete response in participants with CIS with or without resected papillary disease who achieved a complete response at the post-induction (3 month) assessment. This is the number of days from the date of first occurrence of complete response to the date of documented treatment failure or death, whichever occurs first

  Up to 24 months

Secondary Outcomes (8)

• Event-free Survival

  Up to 24 months

• Complete Response Rate at 6, 9, 12, 15, 18, 21, 24 Months

  Participants on treatment were assessed at months 6, 9, 12, 15,18, 21, and 24

• Time to Cystectomy

  Up to 48 months

• Time to Disease Recurrence

  Up to 24 months

• Progression-free Survival

  Up to 24 months

Study Arms (1)

Vicinium

EXPERIMENTAL

Induction - 30 mg of Vicinium in 50 mL of saline administered twice weekly (BIW) for 6 weeks followed by once weekly for 6 weeks, for a total of 12 weeks. Maintenance - 30 mg of Vicinium in 50 mL of saline administered once weekly every other week for up to 104 weeks.

Biological: Vicinium

Interventions

Vicinium BIOLOGICAL

Intravesical administration

Also known as: VB4-845, Oportuzumab monatox

Vicinium

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-confirmed non muscle-invasive urothelial carcinoma (transitional cell carcinoma) of the bladder as follows:
• CIS (with or without papillary disease) OR
• Any grade T1 papillary disease OR
• High-grade Ta papillary disease based on a biopsy within 8 weeks of the initial dose of study treatment. If multiple bladder biopsies are required to confirm eligibility, the last bladder biopsy to the initial dose of study treatment must be within 8 weeks. This diagnosis must be confirmed by the independent central pathology reviewer prior to subject enrollment. A subject with persistent T1 disease on the second (i.e., restaging) TURBT may be enrolled in this study only if the investigator documents the subject declines cystectomy.
• Subjects must have received adequate BCG treatment defined as at least 2 courses of BCG, i.e., at least one induction and one maintenance course or at least 2 induction courses. The initial induction course must be at least 5 treatments within a 7-week period. The second course (induction or maintenance) must be at least 2 treatments within a 6-week period. The "5+2" doses of BCG must be given within approximately 1 year (i.e., the start of one course to start of the second course within 12 months ±1 month) and for the same disease episode for which the subject is enrolling. Treatment must be considered "full-dose" BCG (see Section 10). If additional doses or courses of BCG above the minimum "5+2" are given, these do not have to be within the same approximate 12 month timeframe.
• Subjects who were unable to receive at least 5 doses of BCG in a first course and at least 2 doses of BCG in a second course due to intolerance are not eligible.
• Subjects who began their initial course of BCG with "full-dose" BCG and required dose-reductions due to adverse events but are still able to tolerate at least "5+2" doses of BCG are considered to meet the requirement for "adequate BCG." Subjects who received less than "full dose" BCG (e.g., 1/3rd dosing) as a standard regimen and not due to dose reductions because of AEs are not eligible.
• The BCG may have been given in combination with interferon. When BCG is given simultaneously in combination with interferon, 1/3rd dosing of BCG is acceptable.
• The subject's disease is refractory or has relapsed following adequate BCG treatment. Refractory disease is defined as disease which persists at the first evaluation following adequate BCG. Relapsed disease is defined as having a complete response to adequate BCG but recurs at a subsequent evaluation.
• Subjects will enroll into one of three cohorts based on their type of disease and the time to refractory/relapsed disease following their last dose of BCG as follows:
• Cohort 1: Subjects with CIS with or without associated papillary disease whose disease is determined to be refractory or relapsed within 6 months of the last dose of adequate BCG treatment.
• Cohort 2: Subjects with CIS with or without associated papillary disease whose disease is determined to be refractory or relapsed more than 6 months but within 11 months of the last dose of adequate BCG treatment.
• Cohort 3: Subjects with high-grade Ta or any grade T1 papillary disease (without CIS) whose disease is determined to be refractory or relapsed within 6 months of the last dose of adequate BCG treatment.
• For eligibility and cohort assignment, 6 months is defined as 30 weeks i.e., 26 weeks (6 months) plus an additional 4 weeks to accommodate scheduling variations and for diagnostic work-up and 11 months is defined as 50 weeks i.e., 48 weeks (11 months) plus an additional 2 weeks to accommodate scheduling variations and for diagnostic work-up.
• For subjects enrolling in Cohort 2: The investigator documents he/she would not treat the subject with additional BCG at the time of study entry.

You may not qualify if:

• The subject is pregnant or breastfeeding.
• Evidence of urethral or upper tract transitional cell carcinoma (TCC) within the past 2 years. Subjects with T1 disease must have no evidence of upper or lower tract disease or a more advanced stage of disease by CT urogram or MRI urogram of the abdomen and pelvis performed within 8 weeks of the first dose of study treatment. If intravenous contrast is contraindicated, retrograde ureteropyelography, or CT or MRI without intravenous contrast may be performed.
• Subjects with hydronephrosis, except for those subjects where hydronephrosis has been longstanding (i.e., predates the diagnosis of the CIS, Ta or T1 by more than 2 years) and diagnostic evaluation at Screening shows no evidence of tumor. Subjects with hydronephrosis that is unequivocally unrelated to upper tract malignancy may be considered eligible with Sponsor approval.
• Any intravesicular or other chemotherapy treatment within 2 weeks or any investigational agent within 4 weeks prior to the initial dose of study drug.
• History of recurrent severe urinary tract infections (UTIs) per investigator judgment. Subjects with a current UTI requiring antibiotic treatment may defer the initiation of Vicinium treatment on Day 1 until resolution of the UTI (even if this extends the screening period requirements to start of Vicinium treatment).
• Active, uncontrolled impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic or hematopoietic systems which, in the opinion of the Investigator, would predispose the subject to the development of complications from the administration of intravesical therapy and/or general anesthesia.
• The subject has a diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancer or localized solid tumors deemed cured by surgery and not treated with systemic anticancer therapy and not expected to require anticancer therapy in the next 2 years i.e., while the subject may be taking study treatment. However, subjects with low-risk prostate cancer, e.g.:
• Clinically localized disease (≤T2a) and
• Gleason score 6 (3+3) and
• Serum PSA \<10 ng/mL undergoing active surveillance may be enrolled with agreement of the sponsor.
• A QTc interval of \>470 msec by the Fridericia formula (QTcF), at the Screening ECG. If the subject's QTcF is \>470 msec on the initial ECG, a total of 3 ECGs should be obtained at least 3 minutes apart and all within 30 minutes. The average of the 3 QTcF's will be used to determine eligibility. Known or suspected causes of prolonged QTc can be treated (e.g., hypocalcemia, hypokalemia, hypomagnesimia) and the ECGs may be repeated. If the subject initiates treatment with a drug known to prolong the QTc during the Screening period after the initial Screening ECGs were obtained, the Screening ECGs must be repeated once the new drug has reached steady state to ensure the average QTcF remains ≤470 msec. For subject's whose heart rate is \<60 bpm, the Bazett correction formula (QTcB) may be used.
• 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).
• Local or severe allergy to any components of the drug regimen.

Sponsors & Collaborators

• Sesen Bio, Inc.: lead

Study Sites (70)

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Birmingham, Alabama, 35294, United States

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Phoenix, Arizona, 85032, United States

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Tucson, Arizona, 85741, United States

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Little Rock, Arkansas, 72211, United States

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Los Angeles, California, 90017, United States

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Los Angeles, California, 90048, United States

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Los Angeles, California, 90089, United States

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Los Angeles, California, 90095, United States

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Redwood City, California, 94062, United States

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San Bernardino, California, 92404, United States

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Sherman Oaks, California, 91411, United States

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Torrance, California, 90505, United States

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Englewood, Colorado, 80113, United States

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Washington D.C., District of Columbia, 20010, United States

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Bradenton, Florida, 34205, United States

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Daytona Beach, Florida, 32114, United States

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Orlando, Florida, 32803, United States

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St. Petersburg, Florida, 33710, United States

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Tampa, Florida, 33612, United States

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Wellington, Florida, 33449, United States

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Atlanta, Georgia, 30322, United States

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Honolulu, Hawaii, 96813, United States

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Coeur d'Alene, Idaho, 83814, United States

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Meridian, Idaho, 83642, United States

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Lake Barrington, Illinois, 60010, United States

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Jeffersonville, Indiana, 47130, United States

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Fairway, Kansas, 66205, United States

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Lenexa, Kansas, 66214, United States

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Wichita, Kansas, 67208, United States

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New Orleans, Louisiana, 70112, United States

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Glen Burnie, Maryland, 21061, United States

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Boston, Massachusetts, 02111, United States

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Burlington, Massachusetts, 01805, United States

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Worcester, Massachusetts, 01655, United States

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Ann Arbor, Michigan, 48109, United States

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Lebanon, New Hampshire, 03756, United States

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Brick, New Jersey, 08724, United States

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Lawrenceville, New Jersey, 08648, United States

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Morristown, New Jersey, 07960, United States

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Albuquerque, New Mexico, 87109, United States

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Albany, New York, 12208, United States

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New York, New York, 10032, United States

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Poughkeepsie, New York, 12601, United States

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Syracuse, New York, 13210, United States

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The Bronx, New York, 10461, United States

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Concord, North Carolina, 28025, United States

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Middleburg Heights, Ohio, 44130, United States

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Oklahoma City, Oklahoma, 73014, United States

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Portland, Oregon, 97239, United States

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Bala-Cynwyd, Pennsylvania, 19004, United States

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Bryn Mawr, Pennsylvania, 19010, United States

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Pittsburgh, Pennsylvania, 15232, United States

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Charleston, South Carolina, 29401, United States

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Charleston, South Carolina, 29425, United States

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Dallas, Texas, 75231, United States

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El Paso, Texas, 79920, United States

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Houston, Texas, 68130, United States

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Houston, Texas, 77030, United States

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Temple, Texas, 76508, United States

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Charlottesville, Virginia, 22908, United States

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Richmond, Virginia, 23235, United States

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Halifax, Nova Scotia, B3H 2Y9, Canada

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Barrie, Ontario, L4M 7G1, Canada

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Oakville, Ontario, L6H 3P1, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 2C4, Canada

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Montreal, Quebec, H2X 0A4, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Pointe-Claire, Quebec, H9R 4S3, Canada

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Sherbrooke, Quebec, J1E 3Z6, Canada

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MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

VB4-845

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Dr. Rachelle Dillon
• Organization: Sesen Bio, Inc.

rachelle.dillon@sesenbio.com

204-296-6579

Study Officials

• Minori K Rosales, M.D., Ph.D.

  Sesen Bio

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2015
• First Posted: May 20, 2015
• Study Start: August 1, 2015
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2022
• Last Updated: July 24, 2023
• Results First Posted: July 24, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (9); US (61)