Trial Outcomes & Findings for Sirolimus and Familial Adenomatous Polyposis (FAP) (NCT NCT03095703)

NCT ID: NCT03095703

Last Updated: 2024-10-24

Results Overview

Effect of sirolimus on the size of 5 marked polyps per patient based on video observations.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 4 participants
• Primary outcome timeframe: 6 Months
• Results posted on: 2024-10-24

Participant Flow

Participant milestones

Measure	Sirolimus All patients will receive sirolimus for the duration of the study, with a trough level target range of 5-8 ng/ml. Sirolimus: Participants will be given sirolimus tablets. The starting dose is 2 mg once daily which will be given in 1mg tablets. On day 7 the first trough level is measured (using the LC-MS/MS method) and if not within the target range of 5-8ng/ml, dosing adjustments are made. In case of dosing adjustments, the next trough level is measured seven days later and this is repeated weekly until the target range is achieved. In case trough levels are within the target range, the next trough level measurement is at month 3, after which dosing adjustments are made if necessary, and at month 6. The maximum daily dose is 40mg. No placebo is given.
Overall Study STARTED	4
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

Sirolimus All patients will receive sirolimus for the duration of the study, with a trough level target range of 5-8 ng/ml. Sirolimus: Participants will be given sirolimus tablets. The starting dose is 2 mg once daily which will be given in 1mg tablets. On day 7 the first trough level is measured (using the LC-MS/MS method) and if not within the target range of 5-8ng/ml, dosing adjustments are made. In case of dosing adjustments, the next trough level is measured seven days later and this is repeated weekly until the target range is achieved. In case trough levels are within the target range, the next trough level measurement is at month 3, after which dosing adjustments are made if necessary, and at month 6. The maximum daily dose is 40mg. No placebo is given.

Overall Study Withdrawal by Subject

1

Baseline Characteristics

Sirolimus and Familial Adenomatous Polyposis (FAP)

Baseline characteristics by cohort

Measure	Sirolimus n=4 Participants All patients will receive sirolimus for the duration of the study, with a trough level target range of 5-8 ng/ml. Sirolimus: Participants will be given sirolimus tablets. The starting dose is 2 mg once daily which will be given in 1mg tablets. On day 7 the first trough level is measured (using the LC-MS/MS method) and if not within the target range of 5-8ng/ml, dosing adjustments are made. In case of dosing adjustments, the next trough level is measured seven days later and this is repeated weekly until the target range is achieved. In case trough levels are within the target range, the next trough level measurement is at month 3, after which dosing adjustments are made if necessary, and at month 6. The maximum daily dose is 40mg. No placebo is given.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	50 years n=93 Participants
Sex: Female, Male Female	2 Participants n=93 Participants
Sex: Female, Male Male	2 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	4 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment Netherlands	4 participants n=93 Participants

PRIMARY outcome

Timeframe: 6 Months

Effect of sirolimus on the size of 5 marked polyps per patient based on video observations.

Outcome measures

Measure	Sirolimus n=20 Size of marked polyps All patients will receive sirolimus for the duration of the study, with a trough level target range of 5-8 ng/ml. Sirolimus: Participants will be given sirolimus tablets. The starting dose is 2 mg once daily which will be given in 1mg tablets. On day 7 the first trough level is measured (using the LC-MS/MS method) and if not within the target range of 5-8ng/ml, dosing adjustments are made. In case of dosing adjustments, the next trough level is measured seven days later and this is repeated weekly until the target range is achieved. In case trough levels are within the target range, the next trough level measurement is at month 3, after which dosing adjustments are made if necessary, and at month 6. The maximum daily dose is 40mg. No placebo is given.
Change in Marked Polyp Size Same marked polyp size	4 Size of marked polyps
Change in Marked Polyp Size Decrease in marked polyp size	16 Size of marked polyps
Change in Marked Polyp Size Increase in marked polyp size	0 Size of marked polyps

PRIMARY outcome

Timeframe: 6 Months

Summary analysis of adverse events, clinical laboratory abnormalities and regular physical examination.

Outcome measures

Measure

Sirolimus n=4 Participants All patients will receive sirolimus for the duration of the study, with a trough level target range of 5-8 ng/ml. Sirolimus: Participants will be given sirolimus tablets. The starting dose is 2 mg once daily which will be given in 1mg tablets. On day 7 the first trough level is measured (using the LC-MS/MS method) and if not within the target range of 5-8ng/ml, dosing adjustments are made. In case of dosing adjustments, the next trough level is measured seven days later and this is repeated weekly until the target range is achieved. In case trough levels are within the target range, the next trough level measurement is at month 3, after which dosing adjustments are made if necessary, and at month 6. The maximum daily dose is 40mg. No placebo is given.

Median Number of Treatment-Related Adverse Events Per Participant

10 Number of Adverse Events Interval 4.0 to 16.0

SECONDARY outcome

Timeframe: 6 Months

Number of intestinal polyps was determined by two independent reviewers, blinded for the order of videos (before and after treatment). The median difference comparing baseline en after 6 months of treatment was reported.

Outcome measures

Measure

Sirolimus n=4 Participants All patients will receive sirolimus for the duration of the study, with a trough level target range of 5-8 ng/ml. Sirolimus: Participants will be given sirolimus tablets. The starting dose is 2 mg once daily which will be given in 1mg tablets. On day 7 the first trough level is measured (using the LC-MS/MS method) and if not within the target range of 5-8ng/ml, dosing adjustments are made. In case of dosing adjustments, the next trough level is measured seven days later and this is repeated weekly until the target range is achieved. In case trough levels are within the target range, the next trough level measurement is at month 3, after which dosing adjustments are made if necessary, and at month 6. The maximum daily dose is 40mg. No placebo is given.

Median Difference in Number of Intestinal Polyps

25.75 Median number of polyps Interval 6.5 to 50.0

SECONDARY outcome

Timeframe: 6 Months

The global polyp burden is estimated by the endoscopist and two independent reviewers. The second video in the pair could take the value of -2 (much better), -1 (better), 0 (same), 1 (worse) or 2 (much worse) relative to the first video. Mean scores are calculated for each subject and averaged for the three reviewers. If the assessment of the reviewers differs by more than 1 point from the assessment of the endoscopist, consensus is needed.

Outcome measures

Measure	Sirolimus n=4 Participants All patients will receive sirolimus for the duration of the study, with a trough level target range of 5-8 ng/ml. Sirolimus: Participants will be given sirolimus tablets. The starting dose is 2 mg once daily which will be given in 1mg tablets. On day 7 the first trough level is measured (using the LC-MS/MS method) and if not within the target range of 5-8ng/ml, dosing adjustments are made. In case of dosing adjustments, the next trough level is measured seven days later and this is repeated weekly until the target range is achieved. In case trough levels are within the target range, the next trough level measurement is at month 3, after which dosing adjustments are made if necessary, and at month 6. The maximum daily dose is 40mg. No placebo is given.
Global Polyp Burden Much better	0 Participants
Global Polyp Burden Better	3 Participants
Global Polyp Burden Same	1 Participants
Global Polyp Burden Worse	0 Participants
Global Polyp Burden Much worse	0 Participants

Adverse Events

Sirolimus

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure

Sirolimus n=4 participants at risk All patients will receive sirolimus for the duration of the study, with a trough level target range of 5-8 ng/ml. Sirolimus: Participants will be given sirolimus tablets. The starting dose is 2 mg once daily which will be given in 1mg tablets. On day 7 the first trough level is measured (using the LC-MS/MS method) and if not within the target range of 5-8ng/ml, dosing adjustments are made. In case of dosing adjustments, the next trough level is measured seven days later and this is repeated weekly until the target range is achieved. In case trough levels are within the target range, the next trough level measurement is at month 3, after which dosing adjustments are made if necessary, and at month 6. The maximum daily dose is 40mg. No placebo is given.

Musculoskeletal and connective tissue disorders Desmoid tumor

25.0% 1/4 • Number of events 1 • 6 months The primary objective was to assess the safety outcomes by analysis of adverse events (by monthly telephone calls), laboratory abnormalities and regular physical examination (during hospital visits at 3 and 6 months).

Other adverse events

Measure	Sirolimus n=4 participants at risk All patients will receive sirolimus for the duration of the study, with a trough level target range of 5-8 ng/ml. Sirolimus: Participants will be given sirolimus tablets. The starting dose is 2 mg once daily which will be given in 1mg tablets. On day 7 the first trough level is measured (using the LC-MS/MS method) and if not within the target range of 5-8ng/ml, dosing adjustments are made. In case of dosing adjustments, the next trough level is measured seven days later and this is repeated weekly until the target range is achieved. In case trough levels are within the target range, the next trough level measurement is at month 3, after which dosing adjustments are made if necessary, and at month 6. The maximum daily dose is 40mg. No placebo is given.
Gastrointestinal disorders Gastrointestinal disorders	100.0% 4/4 • Number of events 14 • 6 months The primary objective was to assess the safety outcomes by analysis of adverse events (by monthly telephone calls), laboratory abnormalities and regular physical examination (during hospital visits at 3 and 6 months).
Skin and subcutaneous tissue disorders Skin problems	75.0% 3/4 • Number of events 5 • 6 months The primary objective was to assess the safety outcomes by analysis of adverse events (by monthly telephone calls), laboratory abnormalities and regular physical examination (during hospital visits at 3 and 6 months).

Additional Information

Prof. dr. Evelien Dekker

Amsterdam UMC, location Academic Medical Center

Phone: +3120-5663534

Email: e.dekker@amsterdamumc.nl

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place