Trial Outcomes & Findings for A Pilot Study Evaluating the Use of mTor Inhibitor Sirolimus in Children and Young Adults With Desmoid-Type Fibromatosis (NCT NCT01265030)

Last Updated: 2023-06-26

Results Overview

Changes to the mTOR pathway were determined using an immunohistochemical immunoreactive score (IRS). The components of the IRS for each phosphoprotein (p4EPB and pS706K) are as follows: the percentage of positive cells were scored as: 0 (0%); 1 (\<10%); 2 (11-50%); 3 (51-80%); 4(\>80%). The staining intensity were scored as: 0 (negative), 1 (weak), 2 (moderate), and 3 (strong). To derive the IRS, the percentage of positive cells and staining intensity were multiplied together, resulting in a value from 0 to 12. The score for patients after 4 weeks of sirolimus was compared to a group of control desmoid tumor samples from the UCLA tumor bank (n=68). Lower scores for patients following 4 weeks of sirolimus compared to control sample scores indicate a better outcome.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

9 participants

Primary outcome timeframe

4 weeks

Results posted on

2023-06-26

Participant Flow

Participant milestones

Participant milestones
Measure	Sirolimus Preoperative sirolimus: * loading dose of 12 milligrams/meter2; Per Os (PO), by mouth day 1 (Max dose 12 milligram) * starting 24 hours after the initial loading dose, subjects will receive a dose of 4 milligram/meters2 daily; Per Os (PO), by mouth days 2 through 28 Sirolimus: -Loading dose of 12 milligrams/meter2; Per Os (PO), by mouth day 1 (Max dose 12 milligrams) -Starting 24 hours after the initial loading dose, patients will receive a dose of 4 milligrams/meter2 daily; Per Os (PO), by mouth days 2 through 28 (Max dose 4 milligram/day)
Overall Study STARTED	9
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sirolimus n=9 Participants Preoperative sirolimus: * loading dose of 12 milligrams/meter2; Per Os (PO), by mouth day 1 (Max dose 12 milligram) * starting 24 hours after the initial loading dose, subjects will receive a dose of 4 milligram/meters2 daily; Per Os (PO), by mouth days 2 through 28 Sirolimus: -Loading dose of 12 milligrams/meter2; Per Os (PO), by mouth day 1 (Max dose 12 milligrams) -Starting 24 hours after the initial loading dose, patients will receive a dose of 4 milligrams/meter2 daily; Per Os (PO), by mouth days 2 through 28 (Max dose 4 milligram/day)
Age, Continuous	15 years n=9 Participants
Sex: Female, Male Female	3 Participants n=9 Participants
Sex: Female, Male Male	6 Participants n=9 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: The 9 patients who were treated with sirolimus were compared to a group of control desmoid tumor samples from the UCLA tumor bank (n=68); no identifiable baseline or adverse event data were collected or available from participants who contributed control tumor samples due to anonymization.

Outcome measures

Outcome measures
Measure	Immunoreactive Score Results of p4EPB After 4 Weeks of Sirolimus for the Study Patients n=9 Participants The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein p4EPB for the study patients following 4 weeks of sirolimus is provided.	Immunoreactive Score Results of pS706K After 4 Weeks of Sirolimus for the Study Patients n=9 Participants The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein pS706K for the study patients following 4 weeks of sirolimus is presented.	Immunoreactive Score Results of p4EPB for the Control Tumors n=68 Participants The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein p4EPB for the control tumor samples is presented.	Immunoreactive Score Results of pS706K for the Control Tumors n=68 Participants The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein pS706K for the control tumor samples is presented.
Immunohistochemical Immunoreactive Score Results After 4 Weeks of Sirolimus Compared to Control Specimens	5.22 score on a scale Interval 1.0 to 12.0	7.44 score on a scale Interval 0.0 to 12.0	4.47 score on a scale Interval 0.0 to 12.0	9.39 score on a scale Interval 0.0 to 12.0

SECONDARY outcome

Timeframe: 4 weeks

Population: Pain scores were obtained weekly throughout the 4 week study period in all participants

Pain assessments were performed using the validated numeric (age ≥ 10 years) and Wong-Baker FACES (≥3 and \< 10 years) pain rating scales at specified study time points including baseline, at week 1 and after 4 weeks of treatment (just prior to surgery). Both pain scales range from a value of 0 to 10 with 0 being equal to no pain and 10 being equal to the worst pain. The median pain score and pain score range for study participants at Week 1 and Prior to Surgery (Week 4) timepoints are provided. Lower pain scale values (median and upper limit of the range) at the Prior to Surrgery timepoint are considered a better outcome.

Outcome measures

Outcome measures
Measure	Immunoreactive Score Results of p4EPB After 4 Weeks of Sirolimus for the Study Patients n=9 Participants The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein p4EPB for the study patients following 4 weeks of sirolimus is provided.	Immunoreactive Score Results of pS706K After 4 Weeks of Sirolimus for the Study Patients n=9 Participants The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein pS706K for the study patients following 4 weeks of sirolimus is presented.	Immunoreactive Score Results of p4EPB for the Control Tumors The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein p4EPB for the control tumor samples is presented.	Immunoreactive Score Results of pS706K for the Control Tumors The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein pS706K for the control tumor samples is presented.
Pain Levels After 4 Weeks of Sirolimus	1 score on a scale Interval 0.0 to 3.0	0 score on a scale Interval 0.0 to 3.0	—	—

SECONDARY outcome

Timeframe: 3 years from the end of therapy, a total duration of 3 years and 4 weeks

Population: All trial participants

We evaluated the number of study participants whose tumor did not recur by 3 years from the date of surgery.

Outcome measures

Outcome measures
Measure	Immunoreactive Score Results of p4EPB After 4 Weeks of Sirolimus for the Study Patients n=9 Participants The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein p4EPB for the study patients following 4 weeks of sirolimus is provided.	Immunoreactive Score Results of pS706K After 4 Weeks of Sirolimus for the Study Patients The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein pS706K for the study patients following 4 weeks of sirolimus is presented.	Immunoreactive Score Results of p4EPB for the Control Tumors The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein p4EPB for the control tumor samples is presented.	Immunoreactive Score Results of pS706K for the Control Tumors The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein pS706K for the control tumor samples is presented.
Number of Participants Without Tumor Recurrence	5 Participants	—	—	—

SECONDARY outcome

Timeframe: 4 weeks

Population: All trial participants

The safety and tolerability of patients receiving sirolimus was evaluated using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grading criteria. All reported grades of toxicity (1-5) were collected.

Outcome measures

Outcome measures
Measure	Immunoreactive Score Results of p4EPB After 4 Weeks of Sirolimus for the Study Patients n=9 Participants The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein p4EPB for the study patients following 4 weeks of sirolimus is provided.	Immunoreactive Score Results of pS706K After 4 Weeks of Sirolimus for the Study Patients The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein pS706K for the study patients following 4 weeks of sirolimus is presented.	Immunoreactive Score Results of p4EPB for the Control Tumors The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein p4EPB for the control tumor samples is presented.	Immunoreactive Score Results of pS706K for the Control Tumors The mean immunohistochemical immunoreactive score (IRS) of the phosphoprotein pS706K for the control tumor samples is presented.
Number of Participants With Grade 3 or Higher Toxicity Per CTCAE Definitions	0 Participants	—	—	—

Adverse Events

Sirolimus

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Sirolimus n=9 participants at risk Preoperative sirolimus: * loading dose of 12 milligrams/meter2; Per Os (PO), by mouth day 1 (Max dose 12 milligram) * starting 24 hours after the initial loading dose, subjects will receive a dose of 4 milligram/meters2 daily; Per Os (PO), by mouth days 2 through 28 Sirolimus: -Loading dose of 12 milligrams/meter2; Per Os (PO), by mouth day 1 (Max dose 12 milligrams) -Starting 24 hours after the initial loading dose, patients will receive a dose of 4 milligrams/meter2 daily; Per Os (PO), by mouth days 2 through 28 (Max dose 4 milligram/day)
Nervous system disorders Headache	22.2% 2/9 • Number of events 2 • Adverse events were collected for the duration of treatment (4 weeks).
General disorders Fatigue	22.2% 2/9 • Number of events 2 • Adverse events were collected for the duration of treatment (4 weeks).
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
General disorders Malaise	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Investigations Weight loss	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Nervous system disorders Dizziness	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Gastrointestinal disorders Oral pain	22.2% 2/9 • Number of events 2 • Adverse events were collected for the duration of treatment (4 weeks).
Gastrointestinal disorders Mucositis oral	55.6% 5/9 • Number of events 5 • Adverse events were collected for the duration of treatment (4 weeks).
Skin and subcutaneous tissue disorders Rash maculo-papular	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Vascular disorders Hypertension	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Gastrointestinal disorders Dyspepsia	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Gastrointestinal disorders Constipation	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Gastrointestinal disorders Anal hemorrhage	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Blood and lymphatic system disorders Anemia	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Investigations Lymphocyte count decreased	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Investigations White blood cell decreased	33.3% 3/9 • Number of events 3 • Adverse events were collected for the duration of treatment (4 weeks).
Investigations Neutrophil count decreased	22.2% 2/9 • Number of events 2 • Adverse events were collected for the duration of treatment (4 weeks).
Investigations Creatinine increased	33.3% 3/9 • Number of events 3 • Adverse events were collected for the duration of treatment (4 weeks).
Metabolism and nutrition disorders Hyperglycemia	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Metabolism and nutrition disorders Hypertriglyceridemia	22.2% 2/9 • Number of events 2 • Adverse events were collected for the duration of treatment (4 weeks).
Cardiac disorders Sinus bradycardia	22.2% 2/9 • Number of events 2 • Adverse events were collected for the duration of treatment (4 weeks).
Cardiac disorders Sinus tachycardia	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Vascular disorders Hypotension	44.4% 4/9 • Number of events 4 • Adverse events were collected for the duration of treatment (4 weeks).
Investigations Platelet count decreased	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Gastrointestinal disorders Vomiting	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Gastrointestinal disorders Stomach pain	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Nervous system disorders Sinus pain	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Respiratory, thoracic and mediastinal disorders Nasal congestion	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Musculoskeletal and connective tissue disorders Scoliosis	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Musculoskeletal and connective tissue disorders Back pain	22.2% 2/9 • Number of events 2 • Adverse events were collected for the duration of treatment (4 weeks).
Musculoskeletal and connective tissue disorders Pain in extremity	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
General disorders Facial pain	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Injury, poisoning and procedural complications Fracture	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
Ear and labyrinth disorders Ear pain	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).
General disorders Flu like symptoms	11.1% 1/9 • Number of events 1 • Adverse events were collected for the duration of treatment (4 weeks).

Additional Information

Dr. Aaron Weiss, Principal Investigator

Maine Medical Center

Phone: 2073967565

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place