VESTOR: Phase II Evaluating Efficacy of Temsirolimus in 2 Line Therapy for Patients With Advanced Bladder Cancer

• Sponsor: Institut Bergonié (Other)
• Overall Status: Completed
• CT.gov ID: NCT01827943
• Collaborator: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Enrollment: 54
• Locations: 9
• Arm: 1
• Duration (Months): 90
• Patients Per Site: 6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed Bladder Cancer	Drug: Temsirolimus	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial, Evaluating Efficacy of Temsirolimus (Torisel ®) in Second Line Therapy for Patients With Advanced Bladder Cancer
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Temsirolimus; Temsirolimus; Other Names: Torisel

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHU de Bordeaux	Bordeaux		France	33076
2	Centre François Baclesse	Caen		France	14076
3	Centre Jean Perrin	Clermont Ferrand		France	63011
4	CHU Henri Mondor	Créteil		France	94010
5	Centre Léon Bérard	Lyon		France	69373
6	Hôpital d'instruction des armées du Val-de-Grâce	Paris		France	75230
7	CHU de Rouen	Rouen		France	76031
8	Institut Claudius Regaud	Toulouse		France	31052
9	CHU de Toulouse	Toulouse		France	31059

Sponsors and Collaborators

• Institut Bergonié
• Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Chair: Nadine HOUEDE, MD, Institut Bergonié

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Institut Bergonié
• ClinicalTrials.gov Identifier: NCT01827943
• Other Study ID Numbers: IB2009-08
• First Posted: Apr 10, 2013
• Last Update Posted: May 6, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by Institut Bergonié: Relapsed bladder cancer
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Sirolimus

Study Results

Participant Flow

Arm/Group Title	Temsirolimus
Arm/Group Description	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
Period Title: Overall Study
STARTED	54
Safety Population	53
COMPLETED	45
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Temsirolimus
Arm/Group Description	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
Overall Participants	54
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65.0
Sex: Female, Male (Count of Participants)
Female	12 22.2%
Male	42 77.8%

Outcome Measures

1. Primary Outcome

Title	Non-progression Rate at 2 Months
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temsirolimus
Arm/Group Description	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
Measure Participants	45
Number (95% Confidence Interval) [percentage of participants]	48.9 90.6%

2. Secondary Outcome

Title	Overall Survival
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temsirolimus
Arm/Group Description	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
Measure Participants	45
Median (95% Confidence Interval) [months]	7.2

3. Secondary Outcome

Title	Progression-free Survival
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temsirolimus
Arm/Group Description	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
Measure Participants	45
Median (95% Confidence Interval) [months]	2.8

Adverse Events

Arm/Group Title	Temsirolimus
Arm/Group Description	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
All Cause Mortality
	Temsirolimus
	Affected / at Risk (%)	# Events
Total	40/53 (75.5%)
Serious Adverse Events
	Temsirolimus
	Affected / at Risk (%)	# Events
Total	35/53 (66%)
Blood and lymphatic system disorders
Hemoglobin	3/53 (5.7%)	3
Gastrointestinal disorders
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)	1/53 (1.9%)	1
Mucositis/stomatitis (clinical exam)	2/53 (3.8%)	2
Obstruction, GI	4/53 (7.5%)	5
Vomiting	1/53 (1.9%)	1
General disorders
Fatigue (asthenia, lethargy, malaise)	1/53 (1.9%)	1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	6/53 (11.3%)	7
Constitutional Symptoms - Other (Specify, __)	13/53 (24.5%)	15
Pain - Other (Specify, __)	5/53 (9.4%)	7
Hepatobiliary disorders
Liver dysfunction/failure (clinical)	1/53 (1.9%)	1
Infections and infestations
Infection - Other (Specify, __)	9/53 (17%)	10
Infection with unknown ANC	1/53 (1.9%)	1
Injury, poisoning and procedural complications
Fracture	1/53 (1.9%)	1
Investigations
Platelets	3/53 (5.7%)	3
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)	1/53 (1.9%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other (Specify, __)	1/53 (1.9%)	1
Pain	1/53 (1.9%)	1
Nervous system disorders
Hemorrhage, CNS	2/53 (3.8%)	2
Psychiatric disorders
Confusion	1/53 (1.9%)	1
Mood alteration	1/53 (1.9%)	1
Renal and urinary disorders
Renal failure	2/53 (3.8%)	2
Renal/Genitourinary - Other (Specify, __)	2/53 (3.8%)	2
Urinary retention (including neurogenic bladder)	1/53 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)	1/53 (1.9%)	1
Pulmonary/Upper Respiratory - Other (Specify, __)	3/53 (5.7%)	3
Other (Not Including Serious) Adverse Events
	Temsirolimus
	Affected / at Risk (%)	# Events
Total	53/53 (100%)
Blood and lymphatic system disorders
Hemoglobin	26/53 (49.1%)	40
Gastrointestinal disorders
Constipation	13/53 (24.5%)	13
Diarrhea	15/53 (28.3%)	20
Dry mouth/salivary gland (xerostomia)	3/53 (5.7%)	3
Gastritis (including bile reflux gastritis)	3/53 (5.7%)	3
Gastrointestinal - Other (Specify, __)	3/53 (5.7%)	3
Hemorrhoids	3/53 (5.7%)	5
Mucositis/stomatitis (clinical exam)	19/53 (35.8%)	23
Mucositis/stomatitis (functional/symptomatic)	3/53 (5.7%)	4
Nausea	23/53 (43.4%)	24
Obstruction, GI	6/53 (11.3%)	7
Vomiting	15/53 (28.3%)	19
General disorders
Constitutional Symptoms - Other (Specify, __)	20/53 (37.7%)	21
Fatigue (asthenia, lethargy, malaise)	39/53 (73.6%)	43
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	21/53 (39.6%)	26
Edema:limb	14/53 (26.4%)	14
Pain	29/53 (54.7%)	61
Pain - Other (Specify, __)	5/53 (9.4%)	6
Infections and infestations
Infection - Other (Specify, __)	31/53 (58.5%)	45
Injury, poisoning and procedural complications
Rash/desquamation	8/53 (15.1%)	10
Investigations
Leukocytes (total WBC)	3/53 (5.7%)	4
Platelets	16/53 (30.2%)	24
Weight loss	11/53 (20.8%)	12
Cholesterol, serum-high (hypercholesteremia)	7/53 (13.2%)	7
Metabolism and nutrition disorders
Anorexia	23/53 (43.4%)	26
Dehydration	3/53 (5.7%)	3
Albumin, serum-low (hypoalbuminemia)	3/53 (5.7%)	3
Calcium, serum-low (hypocalcemia)	4/53 (7.5%)	4
Glucose, serum-high (hyperglycemia)	6/53 (11.3%)	6
Metabolic/Laboratory - Other (Specify, __)	3/53 (5.7%)	3
Potassium, serum-high (hyperkalemia)	3/53 (5.7%)	3
Potassium, serum-low (hypokalemia)	4/53 (7.5%)	6
Triglyceride, serum-high (hypertriglyceridemia)	13/53 (24.5%)	16
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other (Specify, __)	6/53 (11.3%)	6
Nervous system disorders
Taste alteration (dysgeusia)	10/53 (18.9%)	10
Dizziness	3/53 (5.7%)	3
Neuropathy: sensory	6/53 (11.3%)	8
Psychiatric disorders
Insomnia	5/53 (9.4%)	5
Mood alteration	13/53 (24.5%)	15
Renal and urinary disorders
Hemorrhage, GU	3/53 (5.7%)	5
Renal failure	9/53 (17%)	10
Renal/Genitourinary - Other (Specify, __)	4/53 (7.5%)	4
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory	6/53 (11.3%)	6
Cough	6/53 (11.3%)	6
Dyspnea (shortness of breath)	6/53 (11.3%)	7
Pulmonary/Upper Respiratory - Other (Specify, __)	4/53 (7.5%)	4
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify, __)	13/53 (24.5%)	20
Dry skin	14/53 (26.4%)	14
Pruritus/itching	8/53 (15.1%)	11
Vascular disorders
Hypertension	4/53 (7.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.