Relapsed Bladder Cancer
Conditions
Keywords
Relapsed bladder cancer
Brief summary
In the absence of standard treatment in this indication, this test evaluates a new drug type targeted therapy in this indication, evaluating its efficacy in terms of tumor response and survival.
Detailed description
In the absence of standard treatment in this indication, this test evaluates a new drug type targeted therapy in this indication, evaluating its efficacy in terms of tumor response and survival. This study will also search for genes involved in the response to treatment.
Interventions
DRUGTemsirolimus
Temsirolimus
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Institut Bergonié
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women of at least 18 years of age * Histologically proven Bladder cancer * Locally advanced or metastatic disease (stage IV) * Functional status (ECOG / OMS) ≤ 2 * Relapse after first-line chemotherapy * Measurable lesions (RECIST criteria) * Absence of anti-neoplasic treatment in the 4 weeks preceding inclusion. * Biological levels : * Neutrophil count \>1,5.109/L. * Platelets \>100.109/L * Total serum bilirubin \< 1.5 × ULN * Clearance of créatinine 40 ml/mm * If not liver metastasis alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5 × ULN * With liver alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<5 × ULN * Signed informed consent * Both women and men must agree to use a medically acceptable method of contraception throughout the study. Women of childbearing potential must have a negative serum pregnancy test of or less than 7 days before the first perfusion of study. * France only : Patients affiliated to a social security program
Exclusion criteria
* Presence of metastatic brain or meningeal tumors on selection scanner, weither symptomatic or asymptomatic * Chemotherapy, immunotherapy, or radiotherapy within 4 weeks of inclusion * Known hypersensitivity to temsirolimus, or its metabolites (as sirolimus), or polysorbate 80 or to their excipients * Previous malignancy (except for cervical carcinoma in situ, basal cell carcinoma curatively treated) or incidental (≤ pT2) prostate cancer found on a radical cystoprostatectomy material * The drugs known as CYP3A4/5 inhibitors or inducers will specifically be excluded on the 30th day ( or at least 7 halves-lives, according to the shortest duration) before the first perfusion and throughout the study. Any food known to inhibit CYP3A4/5 (for example grapefruit, grapefruit juice, star-fruit or star-fruit juice) will also be purposely excluded. * Auto-immune pathology, psychiatric or neurological disorder * Any unstable medical condition * Unstable cardiac disease * Severe renal failure * Unstable diabetes * Pregnancy * Patient enrolled in another therapeutic clinical trial * Patient unable to follow and comply with the study procedures because of any geographical, social or medical condition * Patient partially or totally deprived of his civil rights
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Non-progression Rate at 2 Months | 2 months | Non-progression rate is defined as the rate of participants in complete or partial response or stable disease according to RECIST V1.1. Complete response is defined as the disappearance of all target lesions, partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and stable disease occurs when neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progression, taking as reference the smallest sum diameters while on study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Through Database Cutoff Date of 23-Jan-2015 (up to approximately 5 years and 7 months - median follow-up time of 14 months) | OS was was defined as the time from the treatment initiation to death due to any cause. Participants without documented death were censored at the date of the last follow-up or last patient contact. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. |
| Progression-free Survival | Through Database Cutoff Date of 23-Jan-2015 (up to approximately 5 years and 7 months - median follow-up time of 14 months) | Progression-free survival (PFS) was defined as the time from the initiation of treatment to the first documented progression (as per RECIST v1.1) or death (due to any cause), whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Patients alive and progression free were censored at the date of last follow-up or last patient contact. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Temsirolimus Temsirolimus was administered intravenously at a dose of 25 mg in a weekly 30 min infusion and was associated to anti-H1 treatment. One cycle corresponded to 4 weeks of treatment.
Temsirolimus: Temsirolimus | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Never treated because of an rapid progression | 1 |
| Overall Study | Protocol Violation | 8 |
Baseline characteristics
| Characteristic | Temsirolimus |
|---|---|
| Age, Continuous | 65.0 years |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 40 / 53 |
| other Total, other adverse events | 53 / 53 |
| serious Total, serious adverse events | 35 / 53 |
Outcome results
Primary
Non-progression Rate at 2 Months
Non-progression rate is defined as the rate of participants in complete or partial response or stable disease according to RECIST V1.1. Complete response is defined as the disappearance of all target lesions, partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and stable disease occurs when neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progression, taking as reference the smallest sum diameters while on study.
Time frame: 2 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temsirolimus | Non-progression Rate at 2 Months | 48.9 percentage of participants |
Secondary
Overall Survival
OS was was defined as the time from the treatment initiation to death due to any cause. Participants without documented death were censored at the date of the last follow-up or last patient contact. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data.
Time frame: Through Database Cutoff Date of 23-Jan-2015 (up to approximately 5 years and 7 months - median follow-up time of 14 months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Temsirolimus | Overall Survival | 7.2 months |
Secondary
Progression-free Survival
Progression-free survival (PFS) was defined as the time from the initiation of treatment to the first documented progression (as per RECIST v1.1) or death (due to any cause), whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Patients alive and progression free were censored at the date of last follow-up or last patient contact. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data.
Time frame: Through Database Cutoff Date of 23-Jan-2015 (up to approximately 5 years and 7 months - median follow-up time of 14 months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Temsirolimus | Progression-free Survival | 2.8 months |