An Open-Label, Multicenter, Non-Randomized, Dose-Escalation, Phase 1 Study to Evaluate Safety and Efficacy of Intravesical SN-38 Lipid Suspension in Patients with Non-Muscle Invasive Bladder Cancer
- Conditions
- Health Condition 1: D494- Neoplasm of unspecified behavior of bladder
- Registration Number
- CTRI/2022/05/042539
- Lead Sponsor
- Intas Pharmaceuticals Ltd India
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
Patients are eligible to be included in the study only if all of the following criteria apply: 1 Patient must sign an ICF indicating that the patient understands the purpose of, and procedures required for the study as described in Appendix 10.1.3 in this protocol and is willing to participate in the study. 2 Male or female patient must be greater than or equal to 18 years of age at the time of signing the informed consent. 3 Patients who are medically stable based on medical history, vital signs, physical examination, and 12-lead ECG performed at screening. 4 Patients who are medically stable based on clinical laboratory tests performed at screening. If the results of the serum biochemistry panel, hematology, or urinalysis are outside the normal reference ranges, the patient may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. 5 Have a histologically confirmed diagnosis of non-muscle-invasive urothelial cancer of the urinary bladder based on a biopsy within the 12 weeks prior to baseline visit. If multiple bladder biopsies are required to confirm eligibility, the last bladder biopsy must be within 12 weeks prior to baseline. In case of conflicting result between multiple biopsies, investigator can discuss the case with a pathologist to determine eligibility. Patients with predominant or exclusively non-urothelial histology are not allowed. 6 Patient will be enrolled in the study if they meet criteria for any of the cohorts: Group A: Patients who have undergone bladder biopsies through cystoscopy but have not undergone TURBT and are willing to wait for at least 12 weeks before TURBT. • Group B: Patients who have had complete TURBT and have intermediate or high-risk disease as per AUA/SUO Joint Guideline (2020) (Appendix 10.8). Note: Patients who have already been treated with radiotherapy/chemotherapy /surgery will be enrolled in the above cohorts.7 Have no evidence of urothelial carcinoma involving the upper urinary tract or the urethra (documented with extravesical work up, which may include radiological imaging and/or biopsy) within 3 months prior to baseline. If previous work up occurred more than 3 months prior to baseline, extravesical work up must be repeated prior to baseline in order to determine eligibility. 8 Have elected not to undergo or are considered ineligible for radical cystectomy/partial cystectomy, as determined by the treating surgeon. Reasons for ineligibility or refusal of radical cystectomy/partial cystectomy should be discussed with the patient as part of the informed consent process and should be captured on the appropriate case report form. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 at screening. 10 Adequate renal, hepatic and hematologic parameters. Hematologic parameter ANC greater than or equal to 1500/mm3,Platelet count greater than or equal to 100,000/mm3, Hemoglobin greater than or equal to 9.0 g/dL. Creatinine less than or equal to 1.5 × ULN. If greater than 1.5 × ULN, patient may still be eligible if estimated GFR is greater than 60 mL/min as calculated by the CKD-EPI formula. Alanine transaminase (ALT) and/or aspartate transaminase (AST) less than or equal to 3.0 × upper limit of normal (ULN), Total bilirubin less than or equal to 1.5 × ULN. 11 A female patient is eligible to participate if she is not pregnant or breastfee
Any potential patient who meets any of the following criteria will be excluded from participating in the study 1 Documented medical history of clinically significant pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances or any other medical condition(s) for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol specified assessments. 2 Known allergies, hypersensitivity, contraindication or intolerance to SN-38 lipid suspension, irinotecan or its excipients. 3 Clinically significant active infection including HIV, HBV and HCV testing at screening. 4 History of drug or alcohol abuse within 12 months before Screening 5 Lymphoma, leukemia, or any malignancy except disease under study, within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years, carcinoma in situ of the cervix or malignancy, which is considered cured with minimal risk of recurrence. 6 Current or chronic history of liver disease. This includes but is not limited to hepatitis virus infections, drug- or alcohol-related liver disease, non-alcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilsons disease, alpha-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the investigator. Known hepatic or biliary abnormalities (with the exception of Gilberts syndrome or asymptomatic gallstones). 7 Patients with hydronephrosis, except for those patients where hydronephrosis has been longstanding (i.e., predates the diagnosis of the non-muscle invasive bladder cancer by more than 2 years) and diagnostic evaluation at screening shows no evidence of tumor. Patients with hydronephrosis that is unequivocally unrelated to upper tract malignancy may be considered eligible with Sponsor approval. 8 Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to dose 1, Day 1 or who has not recovered (ie, less or equal to Grade 1 or at baseline) from adverse events due to a previously administered agent. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy). 9 Neo-adjuvant therapy prior to the baseline staging procedure for the current occurrence of non-muscle invasive urothelial carcinoma.10 Patient with known history or current symptoms of any of the following clinically significant cardiac conditions • Unstable angina or myocardial infarction within the past 6 months prior to Screening. • Symptomatic congestive heart failure (CHF) with New York Heart Association (NYHA) functional classification for cardiac disease of Class II or greater within the past 6 months prior to Screening (Appendix 10.6). • Serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality within the past 6 months prior to Screening. • Electrocardiographic evidence of acute ischemic or active conduction system abnormalities at screening assessment. Any other cardiac illness that could lead to a safety risk to the patient within the past 6 months prior to Screening. 11 History of recurrent severe urinary tract
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate the safety and tolerability of intravesical SN-38 lipid suspension for the treatment of adult patients with nonmuscle invasive urothelial carcinoma of urinary bladder at 3 dose levels of 6 doses of weekly instillation to identify the Maximum Tolerated Dose (MTD) 1. Dose level 1, 40 mg per 50 mL 2. Dose level 2, 60 mg per 50 mL3 . Dose level 3, 80 mg per 50 mL.Timepoint: For Group A Proportion of patients with complete response at week twelve and twenty four Event Free Survival rate will be assessed in grp A and B patients till week twenty four.
- Secondary Outcome Measures
Name Time Method To evaluate the anti-tumor activity of intravesical SN lipid suspension for <br/ ><br>the treatment of adult patients with nonmuscle invasive urothelial carcinoma of <br/ ><br>urinary bladderTimepoint: For Group A Proportion of patients with complete response at week twelve and twenty four Event Free Survival rate will be assessed in grp A and B patients till week twenty four