E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced and/or metastatic bladder cancer, which is under control according to first-line chemotherapy. |
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E.1.1.1 | Medical condition in easily understood language |
advanced cancer of the bladder and/or bladder cancer that has spread to other areas of the body, but which is under control as a result of the first treatment given. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005003 |
E.1.2 | Term | Bladder cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the specific cytotoxic T lymphocyte (CTL) response in human leukocyte antigen (HLA)-A*24:02 positive patients receiving S-588410 for 12 weeks. |
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E.2.2 | Secondary objectives of the trial |
● To evaluate the specific CTL induction over time in HLA-A*24:02-positive patients receiving S-588410 for 1 year.
● To estimate antitumor effect in HLA-A*24:02-positive patients receiving S-588410.
● To estimate progression-free survival (PFS) in HLA-A*24:02-positive patients receiving S-588410.
● To estimate overall survival (OS) in HLA-A*24:02-positive patients receiving S-588410.
● To evaluate the safety and tolerability in patients receiving S-588410.
● To assess the general health status in terms of European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and Euro-QOL 5 dimension 5 level version (EQ-5D-5L) questionnaires in HLA-A*24:02-positive patients receiving S- 588410.
● To collect data of tumor evaluation, PFS, OS, and EORTC QLQ-C30 and EQ-5D-5L questionnaires in HLA-A*24:02-negative patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● Patients with advanced and/or metastatic bladder cancer (including urothelial cancer of renal pelvis, ureters, and urethra) who have complete response (CR), partial response (PR), or stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at the end of at least 4 cycles of first line platinum-containing systemic chemotherapy. Common Terminology Criteria for Adverse Events [CTCAE] version 4.03.)
● Patients who are male or female aged ≥20 years at the time of informed consent.
● Patients with the ECOG PS 0 or 1 at enrolment. |
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E.4 | Principal exclusion criteria |
● Patients who have progressive disease (PD) on RECIST version 1.1 at the end of at least 4 cycles of first-line platinum-containing chemotherapy.
● Patients who are judged to have clinically progressive symptoms at the end of at least 4 cycles of first-line platinum-containing chemotherapy by the investigator or subinvestigator.
● Patients with a history of malignant cancer (except for carcinoma in situ or intra-mucosal cancer that resolved with endoscopic therapy) within 5 years before enrollment.
● Patients who received any prior therapies for target disease within 3 weeks before the first administration of S-588410.
● Patients who are expected to require any of the following therapies between enrolment and completion or discontinuation of the study treatment.
– Anti-malignant tumor drug
– Systemic corticosteroid (except for corticosteroid defined as the equivalent of prednisone ≤ 10 mg/day orally)
– Systemic immunosuppressant drug
– Immunotherapy
– Radiotherapy (except for restricted radiotherapy for pain relief of bone metastasis) for the target disease
– Surgical therapy for the target disease
– Hyperthermia for the target disease
– Herbal medicine with anti-tumor or immunosuppressant effect
– Other investigational new products
● Patients who have severe (CTCAE version 4.03 grade 3 or higher) concurrent hepatic impairment, renal impairment, heart disease, hematological disease, respiratory disease, or metabolic disease, with the exception of any symptoms and/or signs associated with target disease.
● Patients who have the following laboratory data with grade 3 or higher according to CTCAE version 4.03 criteria within 28 days before enrolment.
– White blood cell count <2000/mm3 or >100 000/mm3
– Platelet count <50 000/mm3
– Hemoglobin <8.0 g/dL
– Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
>5.0 × the upper limit of normal (ULN)
– Total bilirubin >3.0 × ULN
– Serum creatinine >3.0 × ULN
● Patients who have known human immunodeficiency virus infection.
● Patients with uncontrolled systemic or active infection.
● Patients who had any diseases with the risk of sudden death within 12 months before enrolment.
[Examples]
– Myocardial infarction
– Unstable angina
– Coronary or peripheral artery bypass graft surgery
– Thrombotic or embolic events such as pulmonary embolism, deep vein thrombosis, or transient ischemic attack
● Patients who have known brain metastases.
● Patients with a history or evidence of autoimmune diseases and/or immunodeficiency disorders.
● Patients with a history of severe (CTCAE version 4.03 grade 3 or higher) allergic reaction to a drug, vaccination, or biological preparation.
● Female patients who are lactating or pregnant. Female patients who are of childbearing potential, not included in any of the following, are positive for the pregnancy test at enrolment.
– Postmenopausal woman (at least 2 years since their last regular menstrual period without any other medical reason)
– Women who are surgically sterile by hysterectomy and/or bilateral oophorectomy, or by tubal ligation
● Patients who cannot or do not intend to practice effective contraception (barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel]; hormonal contraceptives [implants, injectables, combination oral contraceptives, or transdermal patches]; or intrauterine devices) as per physicians' recommendations from
enrolment to 90 days after completion or discontinuation of study treatment.
● Patients who received any other investigational products within 28 days or 5 half lives of the investigational products before enrolment whichever is longer. |
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E.5 End points |
E.5.1 | Primary end point(s) |
[S-588410 Group]: CTL induction rate within 12 weeks after initial dose, defined as the proportion of patients who show CTL induction to at least any one of the 5 antigens. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
[S-588410 Group]:
● CTL induction rate within 1 year after initial dose, defined as the proportion of patients who show CTL induction to at least any one of the 5 antigens.
[S-588410 Group and Observation Group]:
● Response rate (RR), defined as the proportion of patients who are assessed as CR or PR by using RECIST version 1.1 and immune-related response criteria (irRC), respectively.
● Disease control rate (DCR), defined as the proportion of patients who are assessed as CR, PR, or SD by using RECIST version 1.1 and irRC, respectively.
● Any response rate in image analysis such as tumor cavitation, defined as the proportion of patients who show any tumor change in image analysis (eg, tumor cavitation).
● PFS, defined as the time interval from the date of enrolment to the date of progression (progression disease based on RECIST version 1.1, clinically progressive
symptoms, or withdrawal due to aggravation of the target disease) or death due to any cause, whichever occurs first.
● OS, defined as the time interval from the date of enrolment to the date of death due to any cause.
● Change in QOL, defined as change from baseline in the global health status, the function scales, and the symptom scales on the EORTC QLQ C30 questionnaire, and the index value and the EQ visual analogue scale (VAS) on the EQ-5D questionnaire, respectively. Baseline is defined as the value obtained at Visit 1 (pre-dose). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Date when evaluation of overall survival is completed. Overall survival assessment will be conducted after 3 years from the enrolment of the last patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |