Trial Outcomes & Findings for RAD001 and Intravesical Gemcitabine in BCG-Refractory Primary or Secondary Carcinoma In Situ of the Bladder (NCT NCT01259063)
NCT ID: NCT01259063
Last Updated: 2018-03-13
Results Overview
Everolimus (mg) given in conjunction with intravesical gemcitabine
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
33 participants
Primary outcome timeframe
8 weeks
Results posted on
2018-03-13
Participant Flow
Participant milestones
| Measure |
Everolimus and Intravesical Gemcitabine
Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase .Everolimus will be continued for 12 months in the patients who achieve a CR or a Partial Response.
|
|---|---|
|
Overall Study
STARTED
|
33
|
|
Overall Study
COMPLETED
|
33
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
RAD001 and Intravesical Gemcitabine in BCG-Refractory Primary or Secondary Carcinoma In Situ of the Bladder
Baseline characteristics by cohort
| Measure |
Pts Who Failed or Relapsed After Intravesical BCG
n=33 Participants
Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase .Everolimus will be continued for 12 months in the patients who achieve a CR or a Partial Response. Patients demonstrating a CR (by cystoscopy and cytology) or a Partial Response at their Cycle 12 cystoscopy will be observed with serial cystoscopies every 3 months.
|
|---|---|
|
Age, Continuous
|
66 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
29 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
33 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: 14 of the 33 participants were enrolled in the Phase I portion of the protocol
Everolimus (mg) given in conjunction with intravesical gemcitabine
Outcome measures
| Measure |
Pts Who Failed or Relapsed After Intravesical BCG
n=14 Participants
Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase I.
|
|---|---|
|
Phase I - Dose-limiting Toxicity (DLT)
|
0 DLT
|
PRIMARY outcome
Timeframe: 1 yearPopulation: 19 participants were evaluable for Phase II.
following start of therapy.
Outcome measures
| Measure |
Pts Who Failed or Relapsed After Intravesical BCG
n=19 Participants
Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase I.
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|---|---|
|
Phase II - Patients Who Are Free of Disease at 1 Year
|
21 percentage of pts disease free at 1 year
Interval 0.0 to 43.0
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: 14 participants enrolled in Phase I
of Everolimus given in conjunction with intravesical gemcitabine
Outcome measures
| Measure |
Pts Who Failed or Relapsed After Intravesical BCG
n=14 Participants
Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase I.
|
|---|---|
|
Phase I - Maximum Tolerated Dose (MTD)
|
10 mg daily of everolimus
|
SECONDARY outcome
Timeframe: 1 yearComplete Response (CR) is defined as no evidence of disease (by cytology and cystoscopy). Partial Response is defined as negative cystoscopy and positive cytology. Progression is defined as the development of invasion or metastasis. If the participant develops a recurrence, they will be considered having failed treatment. Participants will also be considered having failed treatment if there is no response to treatment after two cycles.
Outcome measures
| Measure |
Pts Who Failed or Relapsed After Intravesical BCG
n=33 Participants
Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase I.
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|---|---|
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Complete Response (CR) Rate
Complete Response
|
17 Participants
|
|
Complete Response (CR) Rate
Partial Response
|
8 Participants
|
|
Complete Response (CR) Rate
Did not achieve CR or PR
|
8 Participants
|
SECONDARY outcome
Timeframe: 1 yearWith Everolimus in combination with intravesical gemcitabine. Overall survival following start of therapy will be estimated using Kaplan-Meier methods.
Outcome measures
| Measure |
Pts Who Failed or Relapsed After Intravesical BCG
n=33 Participants
Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase I.
|
|---|---|
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Survival of Patients Treated
|
21 % of pts with CR who relapsed in a year
Interval 0.0 to 43.0
|
SECONDARY outcome
Timeframe: 1 yearPopulation: Inability for sequencing due to inadequate amount of tissue
In all pre-treatment specimens and analysis of post treatment specimens when available.
Outcome measures
Outcome data not reported
Adverse Events
Pts Who Failed or Relapsed After Intravesical BCG
Serious events: 13 serious events
Other events: 23 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
Pts Who Failed or Relapsed After Intravesical BCG
n=33 participants at risk
Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase I.
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|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
3.0%
1/33 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
3.0%
1/33 • 1 year
|
|
Investigations
Alkaline phosphatase increased
|
3.0%
1/33 • 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
6.1%
2/33 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
3.0%
1/33 • 1 year
|
|
General disorders
Chills
|
3.0%
1/33 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.0%
1/33 • 1 year
|
|
Investigations
Creatinine increased
|
3.0%
1/33 • 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
3.0%
1/33 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
9.1%
3/33 • 1 year
|
|
Investigations
Ejection fraction decreased
|
3.0%
1/33 • 1 year
|
|
General disorders
Fever
|
9.1%
3/33 • 1 year
|
|
Gastrointestinal disorders
Gastric ulcer
|
3.0%
1/33 • 1 year
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
3.0%
1/33 • 1 year
|
|
General disorders
Gen disorders & admin site conditions Other, spec
|
3.0%
1/33 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
3.0%
1/33 • 1 year
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify
|
3.0%
1/33 • 1 year
|
|
Injury, poisoning and procedural complications
Injury/poison & proced complications Other, spec
|
3.0%
1/33 • 1 year
|
|
Cardiac disorders
Myocardial infarction
|
3.0%
1/33 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
3.0%
1/33 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
3.0%
1/33 • 1 year
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, specify
|
3.0%
1/33 • 1 year
|
|
Renal and urinary disorders
Urinary frequency
|
3.0%
1/33 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
3.0%
1/33 • 1 year
|
Other adverse events
| Measure |
Pts Who Failed or Relapsed After Intravesical BCG
n=33 participants at risk
Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase I.
|
|---|---|
|
Metabolism and nutrition disorders
Hyperglycemia
|
66.7%
22/33 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
57.6%
19/33 • 1 year
|
|
Investigations
Cholesterol high
|
54.5%
18/33 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
51.5%
17/33 • 1 year
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
51.5%
17/33 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
48.5%
16/33 • 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
42.4%
14/33 • 1 year
|
|
General disorders
Fatigue
|
36.4%
12/33 • 1 year
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, specify
|
36.4%
12/33 • 1 year
|
|
Gastrointestinal disorders
Mucositis oral
|
33.3%
11/33 • 1 year
|
|
Investigations
Platelet count decreased
|
33.3%
11/33 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
27.3%
9/33 • 1 year
|
|
Metabolism and nutrition disorders
Hypernatremia
|
27.3%
9/33 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
24.2%
8/33 • 1 year
|
|
Nervous system disorders
Dysgeusia
|
24.2%
8/33 • 1 year
|
|
Nervous system disorders
Headache
|
24.2%
8/33 • 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
24.2%
8/33 • 1 year
|
|
Investigations
White blood cell decreased
|
24.2%
8/33 • 1 year
|
|
Investigations
Alkaline phosphatase increased
|
21.2%
7/33 • 1 year
|
|
Investigations
Creatinine increased
|
21.2%
7/33 • 1 year
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
18.2%
6/33 • 1 year
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
18.2%
6/33 • 1 year
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
18.2%
6/33 • 1 year
|
|
Renal and urinary disorders
Urinary frequency
|
18.2%
6/33 • 1 year
|
|
General disorders
Edema limbs
|
15.2%
5/33 • 1 year
|
|
Endocrine disorders
Endocrine disorders - Other, specify
|
15.2%
5/33 • 1 year
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
15.2%
5/33 • 1 year
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
15.2%
5/33 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin & subcutaneous tissue disorders Other, spec
|
15.2%
5/33 • 1 year
|
|
Investigations
Weight loss
|
15.2%
5/33 • 1 year
|
|
Injury, poisoning and procedural complications
Burn
|
12.1%
4/33 • 1 year
|
|
Renal and urinary disorders
Cystitis noninfective
|
12.1%
4/33 • 1 year
|
|
General disorders
Fever
|
12.1%
4/33 • 1 year
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
12.1%
4/33 • 1 year
|
|
Investigations
Blood bilirubin increased
|
9.1%
3/33 • 1 year
|
|
Gastrointestinal disorders
Dry mouth
|
9.1%
3/33 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
9.1%
3/33 • 1 year
|
|
Gastrointestinal disorders
Flatulence
|
9.1%
3/33 • 1 year
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
9.1%
3/33 • 1 year
|
|
Renal and urinary disorders
Hematuria
|
9.1%
3/33 • 1 year
|
|
Investigations
Lymphocyte count decreased
|
9.1%
3/33 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
9.1%
3/33 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
6.1%
2/33 • 1 year
|
|
Metabolism and nutrition disorders
Anorexia
|
6.1%
2/33 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
6.1%
2/33 • 1 year
|
|
General disorders
Flu like symptoms
|
6.1%
2/33 • 1 year
|
|
General disorders
Gen disorders & admin site conditions Other, spec
|
6.1%
2/33 • 1 year
|
|
Vascular disorders
Hypertension
|
6.1%
2/33 • 1 year
|
|
Metabolism and nutrition disorders
Hypokalemia
|
6.1%
2/33 • 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
6.1%
2/33 • 1 year
|
|
Investigations
INR increased
|
6.1%
2/33 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
6.1%
2/33 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
6.1%
2/33 • 1 year
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.1%
2/33 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
6.1%
2/33 • 1 year
|
|
Renal and urinary disorders
Urinary incontinence
|
6.1%
2/33 • 1 year
|
|
Renal and urinary disorders
Urinary tract pain
|
6.1%
2/33 • 1 year
|
|
Renal and urinary disorders
Urinary urgency
|
6.1%
2/33 • 1 year
|
Additional Information
Dr. Guido Dalbagni
Memorial Sloan Kettering Cancer Center
Phone: 646-422-4394
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place