Trial Outcomes & Findings for Vismodegib in Treating Patients With Recurrent or Refractory Medulloblastoma (NCT NCT00939484)

Last Updated: 2016-02-25

Results Overview

Objective response is either a complete response or a partial response sustained for 8 weeks in a patient. The objective response rate will be reported separately for patients of each stratum. CR is complete disappearance of all enhancing tumor. PR is \>= 50% reduction in tumor size.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Up to 12 months

Results posted on

2016-02-25

Participant Flow

This study was distributed to the sites on June 18, 2009, and received the first IRB approval on July 20, 2009. The study was closed to accrual on December 07, 2012. Thirty two (32) patients have been enrolled to the study, Last patient went off treatment in October 2013.

Total 32 patients were registered on this study, 8 in Stratum A, 21 in Stratum B and 3 in Stratum C. One patient in Stratum B was declared ineligible.

Participant milestones

Participant milestones
Measure	Stratum A (PTCH/SHH Pathway Inactivated) Adult patients with recurrent or refractory medulloblastoma who have tumors without evidence of PTCH/SHH pathway activation	Stratum B (PTCH/SHH Pathway Activated) Adult patients with recurrent or refractory medulloblastoma who have tumors with evidence of activation of the PTCH/SHH pathway	Stratum C (Unknown PTCH/SHH Pathway Activation) Adult patients with recurrent or refractory medulloblastoma registered on protocol whose tumor assay is inconclusive as to whether or not the PTCH/SHH pathway is activated or whose tissue sample is inadequate to assess the PTCH/SHH pathway status
Overall Study STARTED	8	20	3
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	8	20	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Stratum A (PTCH/SHH Pathway Inactivated) Adult patients with recurrent or refractory medulloblastoma who have tumors without evidence of PTCH/SHH pathway activation	Stratum B (PTCH/SHH Pathway Activated) Adult patients with recurrent or refractory medulloblastoma who have tumors with evidence of activation of the PTCH/SHH pathway	Stratum C (Unknown PTCH/SHH Pathway Activation) Adult patients with recurrent or refractory medulloblastoma registered on protocol whose tumor assay is inconclusive as to whether or not the PTCH/SHH pathway is activated or whose tissue sample is inadequate to assess the PTCH/SHH pathway status
Overall Study Progression/Relapse	8	20	3

Baseline Characteristics

Vismodegib in Treating Patients With Recurrent or Refractory Medulloblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stratum A (PTCH/SHH Pathway Inactivated) n=8 Participants Adult patients with recurrent or refractory medulloblastoma who have tumors without evidence of PTCH/SHH pathway activation	Stratum B (PTCH/SHH Pathway Activated) n=20 Participants Adult patients with recurrent or refractory medulloblastoma who have tumors with evidence of activation of the PTCH/SHH pathway	Stratum C (Unknown PTCH/SHH Pathway Activation) n=3 Participants Adult patients with recurrent or refractory medulloblastoma registered on protocol whose tumor assay is inconclusive as to whether or not the PTCH/SHH pathway is activated or whose tissue sample is inadequate to assess the PTCH/SHH pathway status	Total n=31 Participants Total of all reporting groups
Age, Continuous	23.8 years n=5 Participants	32.0 years n=7 Participants	32.9 years n=5 Participants	30.3 years n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	9 Participants n=7 Participants	2 Participants n=5 Participants	13 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	11 Participants n=7 Participants	1 Participants n=5 Participants	18 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	18 Participants n=7 Participants	2 Participants n=5 Participants	27 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	16 Participants n=7 Participants	3 Participants n=5 Participants	26 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment United States	8 participants n=5 Participants	20 participants n=7 Participants	3 participants n=5 Participants	31 participants n=4 Participants
Diagnosis Desmoplastic medulloblastoma	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Diagnosis Medulloblastoma, NOS	8 participants n=5 Participants	18 participants n=7 Participants	3 participants n=5 Participants	29 participants n=4 Participants
Diagnosis Primitive neuroectodermal tumor	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Outcome measures

Outcome measures
Measure	Stratum A (PTCH/SHH Pathway Inactivated) n=8 Participants Adult patients with recurrent or refractory medulloblastoma who have tumors without evidence of PTCH/SHH pathway activation	Stratum B (PTCH/SHH Pathway Activated) n=20 Participants Adult patients with recurrent or refractory medulloblastoma who have tumors with evidence of activation of the PTCH/SHH pathway	Stratum C (Unknown PTCH/SHH Pathway Activation) n=3 Participants Adult patients with recurrent or refractory medulloblastoma registered on protocol whose tumor assay is inconclusive as to whether or not the PTCH/SHH pathway is activated or whose tissue sample is inadequate to assess the PTCH/SHH pathway status
Objective Response (CR+PR) Sustained for ≥ 8 Weeks	0 proportion of participants Interval 0.0 to 0.37	0.15 proportion of participants Interval 0.03 to 0.38	0 proportion of participants Interval 0.0 to 0.71

SECONDARY outcome

Timeframe: From start of treatment up to 2 years

Progression-free survival (PFS) is measured from the date of initial treatment with GDC-0449 until the earliest of progression or death on study. PFS is censored at the last tumor assessment date for patients without disease progression who have not died within 30 days of last exposure to study treatment. Kaplan-Meier method is used to estimate the progression-free survival.

Outcome measures

Outcome measures
Measure	Stratum A (PTCH/SHH Pathway Inactivated) n=8 Participants Adult patients with recurrent or refractory medulloblastoma who have tumors without evidence of PTCH/SHH pathway activation	Stratum B (PTCH/SHH Pathway Activated) n=20 Participants Adult patients with recurrent or refractory medulloblastoma who have tumors with evidence of activation of the PTCH/SHH pathway	Stratum C (Unknown PTCH/SHH Pathway Activation) n=3 Participants Adult patients with recurrent or refractory medulloblastoma registered on protocol whose tumor assay is inconclusive as to whether or not the PTCH/SHH pathway is activated or whose tissue sample is inadequate to assess the PTCH/SHH pathway status
Progression-free Survival	1.64 months Interval 0.43 to 1.84	2.76 months Interval 1.38 to 6.38	1.48 months Interval 1.38 to 1.84

SECONDARY outcome

Timeframe: From start of treatment up to 2 years

Population: Patients with sustained objective response

The duration of objective response is measured from the initial scan documenting complete or partial response that was subsequently confirmed until the earlier of documented progression or death on study. Duration of objective response is censored at the last tumor assessment date for patients without disease progression who have not died within 30 days of last exposure to study treatment.

Outcome measures

Outcome measures
Measure	Stratum A (PTCH/SHH Pathway Inactivated) n=3 Participants Adult patients with recurrent or refractory medulloblastoma who have tumors without evidence of PTCH/SHH pathway activation	Stratum B (PTCH/SHH Pathway Activated) Adult patients with recurrent or refractory medulloblastoma who have tumors with evidence of activation of the PTCH/SHH pathway	Stratum C (Unknown PTCH/SHH Pathway Activation) Adult patients with recurrent or refractory medulloblastoma registered on protocol whose tumor assay is inconclusive as to whether or not the PTCH/SHH pathway is activated or whose tissue sample is inadequate to assess the PTCH/SHH pathway status
Duration of Objective Response	4.59 months Interval 1.48 to 4.77	—	—

SECONDARY outcome

Timeframe: up to 12 month

Population: The calculation of drug penetration is based on patients who had the course 1 plasma and CSF drug concentration data

The estimated median of cerebrospinal fluid (CSF) drug penetration is reported when expressed as an AUC ratio of CSF vismodegib to that of unbound drug in plasma.

Outcome measures

Outcome measures
Measure	Stratum A (PTCH/SHH Pathway Inactivated) n=28 Participants Adult patients with recurrent or refractory medulloblastoma who have tumors without evidence of PTCH/SHH pathway activation	Stratum B (PTCH/SHH Pathway Activated) Adult patients with recurrent or refractory medulloblastoma who have tumors with evidence of activation of the PTCH/SHH pathway	Stratum C (Unknown PTCH/SHH Pathway Activation) Adult patients with recurrent or refractory medulloblastoma registered on protocol whose tumor assay is inconclusive as to whether or not the PTCH/SHH pathway is activated or whose tissue sample is inadequate to assess the PTCH/SHH pathway status
Pharmacokinetic Parameters of Vismodegib, CSF Penetration	0.12 ratio Interval 0.03 to 0.28	—	—

Adverse Events

Stratum A (PTCH/SHH Pathway Inactivated)

Serious events: 5 serious events

Other events: 8 other events

Deaths: 0 deaths

Stratum B (PTCH/SHH Pathway Activated)

Serious events: 12 serious events

Other events: 20 other events

Deaths: 0 deaths

Stratum C (Unknown PTCH/SHH Pathway Activation)

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Tong Lin (Biostatistician)

St. Jude Children's Research Hospital

Phone: 9015952048

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Stratum A (PTCH/SHH Pathway Inactivated) n=8 participants at risk Adult patients with recurrent or refractory medulloblastoma who have tumors without evidence of PTCH/SHH pathway activation	Stratum B (PTCH/SHH Pathway Activated) n=20 participants at risk Adult patients with recurrent or refractory medulloblastoma who have tumors with evidence of activation of the PTCH/SHH pathway	Stratum C (Unknown PTCH/SHH Pathway Activation) n=3 participants at risk Adult patients with recurrent or refractory medulloblastoma registered on protocol whose tumor assay is inconclusive as to whether or not the PTCH/SHH pathway is activated or whose tissue sample is inadequate to assess the PTCH/SHH pathway status
Blood and lymphatic system disorders Anemia	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Ear and labyrinth disorders Ear pain	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Ear and labyrinth disorders Middle ear inflammation	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Gastrointestinal disorders Dyspepsia	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	66.7% 2/3 • Number of events 2 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
General disorders Death NOS	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	10.0% 2/20 • Number of events 2 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	66.7% 2/3 • Number of events 2 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
General disorders Fever	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Infections and infestations Catheter related infection	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Infections and infestations Lung infection	25.0% 2/8 • Number of events 2 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Infections and infestations Urinary tract infection	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Injury, poisoning and procedural complications Fall	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Investigations Alanine aminotransferase increased	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Investigations GGT increased	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Investigations Weight loss	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Investigations White blood cell decreased	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Metabolism and nutrition disorders Anorexia	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Metabolism and nutrition disorders Dehydration	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Musculoskeletal and connective tissue disorders Muscle weakness trunk	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 2 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Nervous system disorders Headache	25.0% 2/8 • Number of events 2 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	15.0% 3/20 • Number of events 3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Nervous system disorders Hypoglossal nerve disorder	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Nervous system disorders Nystagmus	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Nervous system disorders Peripheral motor neuropathy	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Nervous system disorders Seizure	25.0% 2/8 • Number of events 2 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	33.3% 1/3 • Number of events 2 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Nervous system disorders Somnolence	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Nervous system disorders Syncope	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	33.3% 1/3 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Renal and urinary disorders Urinary incontinence	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Renal and urinary disorders Urinary retention	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Respiratory, thoracic and mediastinal disorders Aspiration	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Respiratory, thoracic and mediastinal disorders Dyspnea	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Vascular disorders Hypotension	12.5% 1/8 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/20 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.
Vascular disorders Thromboembolic event	0.00% 0/8 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	5.0% 1/20 • Number of events 1 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.	0.00% 0/3 • Adverse events were collected non-systematically for each of the participants from the time of enrollment to the completion of therapy or to the time off study.