Study With TMX-101 in Patients With Carcinoma In Situ (CIS) Bladder Cancer
Primary Purpose
Carcinoma in Situ, Non Muscle Invasive Bladder Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
TMX-101
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma in Situ focused on measuring bladder cancer, carcinoma in situ, non muscle invasive bladder cancer
Eligibility Criteria
Inclusion Criteria:
- Males or female patient is aged ≥18 years.
- Pathologically-proven, recurrent, primary, secondary or concomitant carcinoma in situ disease, defined by having either Ta or T1 with CIS, or CIS alone. In cases with T1 tumor lesions, muscularis propria tissue should be in the resected specimen to confirm that it is tumor-free.
- Patient has undergone mapping of the bladder between Days -28 and -14, with at least one biopsy providing pathological confirmation of CIS of the bladder. Slides must be available for a central pathology review.
- Patient has undergone bladder washing for cytology between Days -28 and -1. In patients in whom Ta or T1 lesion(s) were resected, the bladder washing must have occurred after the resection. Slides must be available for a central cytology review.
- Patient has an ECOG performance status 0-2.
- Patient has adequate bone marrow, hepatic, and renal function within 4 weeks before Day 0.
- Patient has read and understood the informed consent form and is willing and able to give informed consent.
- Patient fully understands the requirements of the study and is willing to comply with all study visits and assessments.
- If a woman of childbearing potential (WCBP), patient has a negative blood pregnancy test at the Screening visit. For the purposes of this study, WCBP is defined as a post-pubescent female, unless post-menopausal for at least 2 years, surgically sterile, or sexually inactive.
- If patient is a WCPB or male patient with a female partner of childbearing potential, must be willing to avoid pregnancy by using an adequate method of contraception from 2 weeks before through 4 weeks after the last study drug treatment. Adequate contraception is defined as follows: 2 barrier methods or 1 barrier method with a spermicide or intrauterine device.
Exclusion Criteria:
- Patient has evidence of muscle-invasive disease (i.e., T2 or higher)
- In the Investigator's opinion, patient is not able to hold instillation for at least 1 hour.
- In the Investigator's opinion, patient cannot tolerate intravesical administration or intravesical surgical manipulation.
- Patient has received radiation therapy of pelvis within 12 months before the first study drug treatment.
- Patient requires perioperative intravesical chemotherapy.
- Patient has a history of malignancy of the upper urinary tract.
Patient has bone marrow impairment as evidenced by:
- Hemoglobin <9.0 g/dL
- Absolute neutrophil count (ANC) <1.5×109/L
- Platelet count <120×109/L.
Patient has renal impairment, as evidenced by:
- Serum creatinine >2× the upper limit of normal (ULN), and/or
- Calculated creatinine clearance <40 mL/min.
Patient has liver function abnormality, as evidenced by:
- Total bilirubin >1.5×ULN, or
- Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) >2.5×ULN.
- Patient has a bleeding disorder, as evidenced by an international normalized ratio (INR) >1.5×ULN.
- Patient is known to be positive for human immunodeficiency virus (HIV) or has active hepatitis B or C infection.
- Patient has a clinically significant active infection at the time of the first study drug treatment.
- Patient has any medical or psychiatric condition that, in the Investigator's opinion, might impair the patient's well-being or preclude adherence to the protocol or completing the study as per protocol.
- Patient has suspected hypersensitivity to imidazoquinoline compounds, poloxamer 407, hydroxy propyl betacyclodextrin, or lactic acid.
- If female, patient is pregnant or breast feeding.
- Patient participated in any other protocol involving administration of an investigational agent within 3 months before Day 0.
Sites / Locations
- BCG Oncology
- The Urology Center of Colorado
- Urologic Consultants of SE PA
- Carolina Urologic Research Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TMX-101
Arm Description
TMX-101 0.4% (200 mg in 50 ml) instilled in the bladder once weekly for 6 weeks
Outcomes
Primary Outcome Measures
To assess the activity of TMX-101, as determined by the number of patients who experience complete response (CR).
Secondary Outcome Measures
Proportion of patients experiencing adverse events (AEs), including serious adverse events (SAEs) and AEs leading to discontinuation from the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01731652
Brief Title
Study With TMX-101 in Patients With Carcinoma In Situ (CIS) Bladder Cancer
Official Title
Phase II Pilot Study With TMX 101 in Patients With Carcinoma In Situ (CIS) Bladder Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
October 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Telormedix SA
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase II pilot study to explore the effect of intravesical TMX-101 in patients with CIS bladder cancer, as assessed by histology and cytology after TMX-101 treatment.
Detailed Description
This study is an open label, pilot study of TMX-101 in the treatment of carcinoma in situ. TMX-101 is a new formulation of Imiquimod optimized for intravesical delivery. Imiquimod possesses immune-stimulatory properties. TMX-101 is being developed as a potential treatment for patients with non-invasive bladder cancer, including patients with CIS bladder cancer.
Following confirmation of CIS by histology, patients will receive weekly instillations of TMX-101 for 6 weeks. Five to seven weeks after the last instillation, biopsies and cytology will be performed. Response to treatment will be determined based on cytology and tissue sample histology findings.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma in Situ, Non Muscle Invasive Bladder Cancer
Keywords
bladder cancer, carcinoma in situ, non muscle invasive bladder cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TMX-101
Arm Type
Experimental
Arm Description
TMX-101 0.4% (200 mg in 50 ml) instilled in the bladder once weekly for 6 weeks
Intervention Type
Drug
Intervention Name(s)
TMX-101
Other Intervention Name(s)
Imiquimod
Primary Outcome Measure Information:
Title
To assess the activity of TMX-101, as determined by the number of patients who experience complete response (CR).
Time Frame
5 to 7 weeks after the last TMX -101 instillation
Secondary Outcome Measure Information:
Title
Proportion of patients experiencing adverse events (AEs), including serious adverse events (SAEs) and AEs leading to discontinuation from the study.
Time Frame
Patients will be followed through treatment and follow-up, for an expected total period of up to 13 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or female patient is aged ≥18 years.
Pathologically-proven, recurrent, primary, secondary or concomitant carcinoma in situ disease, defined by having either Ta or T1 with CIS, or CIS alone. In cases with T1 tumor lesions, muscularis propria tissue should be in the resected specimen to confirm that it is tumor-free.
Patient has undergone mapping of the bladder between Days -28 and -14, with at least one biopsy providing pathological confirmation of CIS of the bladder. Slides must be available for a central pathology review.
Patient has undergone bladder washing for cytology between Days -28 and -1. In patients in whom Ta or T1 lesion(s) were resected, the bladder washing must have occurred after the resection. Slides must be available for a central cytology review.
Patient has an ECOG performance status 0-2.
Patient has adequate bone marrow, hepatic, and renal function within 4 weeks before Day 0.
Patient has read and understood the informed consent form and is willing and able to give informed consent.
Patient fully understands the requirements of the study and is willing to comply with all study visits and assessments.
If a woman of childbearing potential (WCBP), patient has a negative blood pregnancy test at the Screening visit. For the purposes of this study, WCBP is defined as a post-pubescent female, unless post-menopausal for at least 2 years, surgically sterile, or sexually inactive.
If patient is a WCPB or male patient with a female partner of childbearing potential, must be willing to avoid pregnancy by using an adequate method of contraception from 2 weeks before through 4 weeks after the last study drug treatment. Adequate contraception is defined as follows: 2 barrier methods or 1 barrier method with a spermicide or intrauterine device.
Exclusion Criteria:
Patient has evidence of muscle-invasive disease (i.e., T2 or higher)
In the Investigator's opinion, patient is not able to hold instillation for at least 1 hour.
In the Investigator's opinion, patient cannot tolerate intravesical administration or intravesical surgical manipulation.
Patient has received radiation therapy of pelvis within 12 months before the first study drug treatment.
Patient requires perioperative intravesical chemotherapy.
Patient has a history of malignancy of the upper urinary tract.
Patient has bone marrow impairment as evidenced by:
Hemoglobin <9.0 g/dL
Absolute neutrophil count (ANC) <1.5×109/L
Platelet count <120×109/L.
Patient has renal impairment, as evidenced by:
Serum creatinine >2× the upper limit of normal (ULN), and/or
Calculated creatinine clearance <40 mL/min.
Patient has liver function abnormality, as evidenced by:
Total bilirubin >1.5×ULN, or
Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) >2.5×ULN.
Patient has a bleeding disorder, as evidenced by an international normalized ratio (INR) >1.5×ULN.
Patient is known to be positive for human immunodeficiency virus (HIV) or has active hepatitis B or C infection.
Patient has a clinically significant active infection at the time of the first study drug treatment.
Patient has any medical or psychiatric condition that, in the Investigator's opinion, might impair the patient's well-being or preclude adherence to the protocol or completing the study as per protocol.
Patient has suspected hypersensitivity to imidazoquinoline compounds, poloxamer 407, hydroxy propyl betacyclodextrin, or lactic acid.
If female, patient is pregnant or breast feeding.
Patient participated in any other protocol involving administration of an investigational agent within 3 months before Day 0.
Facility Information:
Facility Name
BCG Oncology
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85032
Country
United States
Facility Name
The Urology Center of Colorado
City
Denver
State/Province
Colorado
ZIP/Postal Code
80211
Country
United States
Facility Name
Urologic Consultants of SE PA
City
Bala Cynwyd
State/Province
Pennsylvania
ZIP/Postal Code
19004
Country
United States
Facility Name
Carolina Urologic Research Center
City
Myrtle Beach
State/Province
South Carolina
ZIP/Postal Code
29572
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28341495
Citation
Donin NM, Chamie K, Lenis AT, Pantuck AJ, Reddy M, Kivlin D, Holldack J, Pozzi R, Hakim G, Karsh LI, Lamm DL, Belkoff LH, Belldegrun AS, Holden S, Shore N. A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer. Urol Oncol. 2017 Feb;35(2):39.e1-39.e7. doi: 10.1016/j.urolonc.2016.09.006. Epub 2016 Oct 26.
Results Reference
derived
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Study With TMX-101 in Patients With Carcinoma In Situ (CIS) Bladder Cancer
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