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Codex: Study of Inodiftagene Vixteplasmid (BC-819) in Unresponsive NMIBC

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ClinicalTrials.gov Identifier: NCT03719300
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : September 24, 2019
Sponsor:
Information provided by (Responsible Party):
Anchiano Therapeutics Israel Ltd.

Brief Summary:
This study, BC-819-18-204, is a Phase 2, open-label, monotherapy, single-arm, multicenter clinical trial of BC-819 (inodiftagene vixteplasmid) in patients with NMIBC adequately treated with Bacillus Calmette-Guerin (BCG) whose disease is BCG unresponsive according to the US Food and Drug Administration (FDA) guidance.

Condition or disease Intervention/treatment Phase
Non-muscle Invasive Bladder Cancer (NMIBC) Drug: inodiftagene vixteplasmid Phase 2

Detailed Description:
BC-819 (inodiftagene vixteplasmid) is a recombinant DNA plasmid that directs the expression of a potent toxin specifically in malignant cells but not in normal tissue. It has been designed to exploit the established biology of the H19 gene, which is upregulated and expressed at high levels only in malignant cells, to produce bacterial diphtheria toxin only in bladder cancer tissue. BC-819 is administered directly into the bladder to enable maximal topical exposure to target bladder cancer cells.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of BC-819 in Patients With Non-Muscle Invasive Bladder Cancer Whose Disease is Unresponsive to Bacillus Calmette-Guerin
Actual Study Start Date : December 11, 2018
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: Single Arm BC-819
inodiftagene vixteplasmid
Drug: inodiftagene vixteplasmid

BC-819 at 20 mg/50 mL, instilled intravesically into the bladder, with a retention time of at least 30 minutes (up to 2 hours).

Induction Phase (weekly treatments): 10 weekly treatments; Maintenance Phase: treatment every 3 weeks for up to 84 additional weeks

Other Name: BC-819




Primary Outcome Measures :
  1. Complete response rate [ Time Frame: 12-48 weeks ]
    Complete response rate anytime on or after 12 weeks and within the first 48 weeks in patients with carcinoma in situ (CIS)


Secondary Outcome Measures :
  1. High-grade recurrence free survival [ Time Frame: 48 weeks ]
    The incidence of Event Free Survival (EFS) at 48 weeks in all patients, where EFS is defined as high-grade recurrence free survival

  2. High-grade recurrence free survival [ Time Frame: 12, 24, 36, 72, and 96 weeks ]
    The incidence of EFS at 12, 24, 36, 72, and 96 weeks, where EFS is defined as high-grade recurrence free survival (overall population and subgroup of patients with CIS)

  3. Time to recurrence [ Time Frame: 12, 24, 36, 72, and 96 weeks ]
    Time to recurrence; recurrence is defined as an EFS event

  4. Progression-free survival [ Time Frame: 48, 72, and 96 weeks ]
    The incidence of progression-free survival at 48, 72, and 96 weeks as well as time to progression estimated using Kaplan-Meir methods.

  5. Overall survival of patients [ Time Frame: 48, 72, and 96 weeks ]
    Overall survival of patients enrolled in the study at 48, 72, and 96 weeks and survival time estimated using Kaplan-Meier methods

  6. Changes in quality of life (EORTC QLQ-C30) over time [ Time Frame: 48, 72, and 96 weeks ]
    Changes in quality of life over time, as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30; a general questionnaire for cancer) The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status/QoL scale and six single items. All scales range in score from 0 to 100. A high scale score represents a higher response level.

  7. Changes in quality of life (QLQ-NMIBC24) over time [ Time Frame: 48, 72, and 96 weeks ]
    Changes in quality of life over time, as measured by Non-Muscle Invasive Bladder Cancer Questionnaire (QLQ-NMIBC24; a specific questionnaire for NMIBC disease) The questionnaire assesses urinary symptoms, bowel symptoms, and sexual functioning as well as side effects of intravesical treatment (fever, malaise, etc).

  8. Duration of complete response rate [ Time Frame: 12-48 weeks ]
    Duration of complete response in patients with CIS.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients ≥18 years of age at the time of consent
  2. Patient must have been adequately treated with BCG defined as at least one of the following (FDA 2018):

    1. At least five of six doses of an initial induction course plus at least two of three doses of maintenance therapy
    2. At least five of six doses of an initial induction course plus at least two of six doses of a second induction course
    3. A single course of induction BCG can qualify if the patient has T1 high-grade disease at first evaluation (see 3c)
  3. Patient must be BCG-unresponsive defined as at least one of the following (FDA 2018):

    1. Persistent or recurrent CIS alone or with recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy. An assessment within 15 months can also qualify when no assessment was done 12 months after completion of adequate BCG therapy.
    2. Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy. An assessment within 9 months can also qualify when no assessment was done 6 months after completion of adequate BCG therapy.
    3. T1 high-grade disease at the first evaluation following a single course of induction BCG qualifies (Lerner et al. 2015, Steinberg et al. 2016)
  4. Patient must have, at study entry, NMIBC indicated by 1 or more of the following:

    1. Ta or T1 high-grade disease
    2. CIS disease
  5. Patient must have no known evidence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra within 6 months of enrollment
  6. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  7. Patient must have adequate hematologic function, as demonstrated by the following:

    1. Hemoglobin level ≥10 g/dL
    2. Absolute neutrophil count ≥1.5 x 109/L
    3. Platelet count ≥100 x 109/L
  8. Patient must have adequate liver and renal function as demonstrated by the following:

    1. Aspartate aminotransferase and alanine aminotransferase each ≤3.0 x upper limit of normal
    2. Total bilirubin ≤1.5 x upper limit of normal, unless prior documentation of Gilbert's syndrome in which case, 3.0 mg/dL is allowed
    3. Serum creatinine ≤1.5 x upper limit of normal or measured or calculated creatinine clearance ≥30 mL/min
  9. Female patients of childbearing potential must use maximally effective birth control during the period of therapy and for 1 month after the last study drug infusion
  10. Male patients who are sexually active must be willing to use a double barrier contraceptive method upon study enrollment, during the course of the study, and for 1 month after the last study drug infusion

Exclusion Criteria:

  1. Patient has current or previous evidence of muscle invasive (muscularis propria) or metastatic bladder cancer disease
  2. Patient has received prior investigational therapy for NMIBC
  3. Patient has received any therapy for NMIBC within 10 weeks before the start of study treatment other than surgical resection, 1 dose of chemotherapy, and previous BCG
  4. Patient is intolerant to previous BCG treatment in the absence of meeting other criteria for BCG unresponsiveness and adequate BCG therapy
  5. Patient has received external beam radiation therapy for bladder cancer at any time or for any other condition
  6. Patient has an active infection, including urinary tract infection (viral, bacterial, or fungal) and cystitis
  7. Patient has urinary tract signs or symptoms that preclude retention of drug in the bladder; this does not include anticholinergic drugs
  8. Patient is known to have tested positive for human immunodeficiency virus (HIV). No HIV testing is required if patient is not known have tested positive
  9. Patient is female and is pregnant or breastfeeding
  10. Patient has a known presence or history of malignancy of other organ system within the 5 years before study start, with the exception of non-melanoma skin cancer; very low or low-risk prostate cancer; or patients who have been disease free for at least 2 years following stage 1 or 2 cancer

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03719300


Contacts
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Contact: Sean T Daly 857-277-5577 sean.daly@anchiano.com

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Sponsors and Collaborators
Anchiano Therapeutics Israel Ltd.

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Responsible Party: Anchiano Therapeutics Israel Ltd.
ClinicalTrials.gov Identifier: NCT03719300     History of Changes
Other Study ID Numbers: BC-819-18-204
First Posted: October 25, 2018    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Anchiano Therapeutics Israel Ltd.:
BCG-unresponsive
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases