Trial Outcomes & Findings for Sirolimus to Treat Cowden Syndrome and Other PTEN Hamartomatous Tumor Syndromes (NCT NCT00971789)
NCT ID: NCT00971789
Last Updated: 2015-09-30
Results Overview
A biochemical change is defined as a decrease in certain protein levels (e.g. P-AKT (phosphorylated AKT), total S6, P-S6, and P-4E-BP1) important in cell growth. These are measured by collecting tissue samples which stained and protein levels are measured under the microscope. Scoring will be based on distribution and intensity of staining. Distribution will be scored as 0 (0%), 1 (1% to 50%), and 2 (51% to 100%) to indicate the percentage of positive cells of interest in a single core. The intensity of the signal will be scored as 1 (weak), 2 (moderate), and 3 (strong). The distribution score and intensity score will be summed into a total score (TS).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
18 participants
Primary outcome timeframe
Baseline, day 14, and day 56
Results posted on
2015-09-30
Participant Flow
Participant milestones
| Measure |
Sirolimus Patients
sirolimus 6 mg by mouth loading dose and 2 mg by mouth daily in a 28 day treatment cycle. Patients who do not have cancer take the drug for a total of two cycles (56 days) unless they develop unacceptable side effects. Those who have cancer may continue sirolimus beyond cycle 2 until their disease worsens or they develop unacceptable side effects.
|
|---|---|
|
Overall Study
STARTED
|
18
|
|
Overall Study
COMPLETED
|
18
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Sirolimus to Treat Cowden Syndrome and Other PTEN Hamartomatous Tumor Syndromes
Baseline characteristics by cohort
| Measure |
Sirolimus Patients
n=18 Participants
sirolimus 6 mg by mouth loading dose and 2 mg by mouth daily in a 28 day treatment cycle. Patients who do not have cancer take the drug for a total of two cycles (56 days) unless they develop unacceptable side effects. Those who have cancer may continue sirolimus beyond cycle 2 until their disease worsens or they develop unacceptable side effects.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=99 Participants
|
|
Age, Continuous
|
43.54 years
STANDARD_DEVIATION 15.54 • n=99 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
18 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline, day 14, and day 56Population: No patient underwent biopsy after the study treatment, so no such tissue analysis was done.
A biochemical change is defined as a decrease in certain protein levels (e.g. P-AKT (phosphorylated AKT), total S6, P-S6, and P-4E-BP1) important in cell growth. These are measured by collecting tissue samples which stained and protein levels are measured under the microscope. Scoring will be based on distribution and intensity of staining. Distribution will be scored as 0 (0%), 1 (1% to 50%), and 2 (51% to 100%) to indicate the percentage of positive cells of interest in a single core. The intensity of the signal will be scored as 1 (weak), 2 (moderate), and 3 (strong). The distribution score and intensity score will be summed into a total score (TS).
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 47 monthsHere is the number of participants with adverse events
Outcome measures
| Measure |
Sirolimus Patients
n=18 Participants
sirolimus 6 mg by mouth loading dose and 2 mg by mouth daily in a 28 day treatment cycle. Patients who do not have cancer take the drug for a total of two cycles (56 days) unless they develop unacceptable side effects. Those who have cancer may continue sirolimus beyond cycle 2 until their disease worsens or they develop unacceptable side effects.
|
|---|---|
|
Number of Participants With Adverse Events
|
17 Participants
|
Adverse Events
Sirolimus Patients
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sirolimus Patients
n=18 participants at risk
sirolimus 6 mg by mouth loading dose and 2 mg by mouth daily in a 28 day treatment cycle. Patients who do not have cancer take the drug for a total of two cycles (56 days) unless they develop unacceptable side effects. Those who have cancer may continue sirolimus beyond cycle 2 until their disease worsens or they develop unacceptable side effects.
|
|---|---|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
11.1%
2/18 • Number of events 3
|
|
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
|
38.9%
7/18 • Number of events 12
|
|
Metabolism and nutrition disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)
|
16.7%
3/18 • Number of events 5
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
38.9%
7/18 • Number of events 9
|
|
Metabolism and nutrition disorders
Alkaline phosphatase
|
27.8%
5/18 • Number of events 5
|
|
Blood and lymphatic system disorders
Blood/Bone Marrow - Other (anemia)
|
5.6%
1/18 • Number of events 1
|
|
Blood and lymphatic system disorders
CD4 count
|
5.6%
1/18 • Number of events 1
|
|
Metabolism and nutrition disorders
Calcium, serum-high (hypercalcemia)
|
11.1%
2/18 • Number of events 2
|
|
Metabolism and nutrition disorders
Cholesterol, serum-high (hypercholesteremia)
|
27.8%
5/18 • Number of events 5
|
|
Gastrointestinal disorders
Constipation
|
22.2%
4/18 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.6%
1/18 • Number of events 1
|
|
Gastrointestinal disorders
Dental: teeth
|
5.6%
1/18 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
6/18 • Number of events 9
|
|
Gastrointestinal disorders
Distension/bloating, abdominal
|
5.6%
1/18 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
16.7%
3/18 • Number of events 3
|
|
Blood and lymphatic system disorders
Edema: limb
|
11.1%
2/18 • Number of events 2
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
38.9%
7/18 • Number of events 7
|
|
Gastrointestinal disorders
Flatulence
|
5.6%
1/18 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis (including bile reflux gastritis)
|
5.6%
1/18 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal - Other (bloating)
|
5.6%
1/18 • Number of events 1
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
16.7%
3/18 • Number of events 4
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)
|
11.1%
2/18 • Number of events 2
|
|
Metabolism and nutrition disorders
Hemoglobin
|
38.9%
7/18 • Number of events 9
|
|
Gastrointestinal disorders
Hemorrhage, GI::Colon
|
5.6%
1/18 • Number of events 1
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Eye NOS
|
5.6%
1/18 • Number of events 1
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis)
|
5.6%
1/18 • Number of events 1
|
|
Infections and infestations
Infection with unknown ANC::Sinus
|
5.6%
1/18 • Number of events 1
|
|
General disorders
Insomnia
|
22.2%
4/18 • Number of events 5
|
|
Reproductive system and breast disorders
Irregular menses (change from baseline)
|
5.6%
1/18 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
11.1%
2/18 • Number of events 2
|
|
Metabolism and nutrition disorders
Lipase
|
5.6%
1/18 • Number of events 1
|
|
Blood and lymphatic system disorders
Lymphopenia
|
16.7%
3/18 • Number of events 5
|
|
Metabolism and nutrition disorders
Magnesium, serum-high (hypermagnesemia)
|
22.2%
4/18 • Number of events 4
|
|
Metabolism and nutrition disorders
Magnesium, serum-low (hypomagnesemia)
|
16.7%
3/18 • Number of events 4
|
|
Nervous system disorders
Memory impairment
|
5.6%
1/18 • Number of events 1
|
|
Nervous system disorders
Mood alteration::Depression
|
5.6%
1/18 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam)::Oral cavity
|
16.7%
3/18 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
11.1%
2/18 • Number of events 2
|
|
Nervous system disorders
Neuropathy: sensory
|
11.1%
2/18 • Number of events 2
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
5.6%
1/18 • Number of events 1
|
|
Blood and lymphatic system disorders
PTT (Partial Thromboplastin Time)
|
5.6%
1/18 • Number of events 2
|
|
General disorders
Pain - Other (R/costal vert. angle; R/flank; shoulder)
|
11.1%
2/18 • Number of events 3
|
|
Gastrointestinal disorders
Pain::Abdomen NOS
|
11.1%
2/18 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Pain::Extremity-limb
|
5.6%
1/18 • Number of events 1
|
|
Nervous system disorders
Pain::Head/headache
|
22.2%
4/18 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Pain::Joint
|
11.1%
2/18 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain::Muscle
|
11.1%
2/18 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Pain::Neck
|
5.6%
1/18 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pain::Throat/pharynx/larynx
|
5.6%
1/18 • Number of events 1
|
|
Metabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)
|
16.7%
3/18 • Number of events 6
|
|
Blood and lymphatic system disorders
Platelets
|
5.6%
1/18 • Number of events 1
|
|
Metabolism and nutrition disorders
Proteinuria
|
5.6%
1/18 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
5.6%
1/18 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash: acne/acneiform
|
5.6%
1/18 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash: hand-foot skin reaction
|
11.1%
2/18 • Number of events 2
|
|
General disorders
Rigors/chills
|
5.6%
1/18 • Number of events 1
|
|
Metabolism and nutrition disorders
Sodium, serum-high (hypernatremia)
|
5.6%
1/18 • Number of events 1
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
11.1%
2/18 • Number of events 2
|
|
Metabolism and nutrition disorders
Triglyceride, serum-high (hypertriglyceridemia)
|
27.8%
5/18 • Number of events 5
|
|
Metabolism and nutrition disorders
Uric acid, serum-high (hyperuricemia)
|
5.6%
1/18 • Number of events 1
|
|
Renal and urinary disorders
Urine color change
|
5.6%
1/18 • Number of events 1
|
|
Vascular disorders
Vascular - Other (venous insufficiency)
|
5.6%
1/18 • Number of events 1
|
Additional Information
Dr. Arun Rajan
National Cancer Institute, National Institutes of Health
Phone: 301-594-5322
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place