Trial Outcomes & Findings for Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure. (NCT NCT01878890)

Last Updated: 2021-01-27

Results Overview

MTD was determined by testing increasing doses up to 3000 mg (oral daily intake). The dose escalation scheme is the continual reassessment method likehood approach (CRML) described by O'Quigley and Shen \[O'Quigley et al. Biometrics 1996\]. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 25% of participants. A DLT was any drug-related toxicity with grade ≥ 3 according to NCI-CTCAE v4.0 (except alopecia, nausea and vomiting, regardless of grade), any drug-related toxicity, regardless of grade, who led a treatment delay\> 14 days, a score ≥ 19 for the Hospital Anxiety And Depression Scale (HAD) during treatment.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

25 participants

Primary outcome timeframe

Up to 28 days for each dosing cohort

Results posted on

2021-01-27

Participant Flow

Participant milestones

Participant milestones
Measure	Efavirenz - 600 mg Participants received 600 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz - 1200 mg Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz - 1800 mg Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz - 2200 mg Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity.
Overall Study STARTED	5	11	4	5
Overall Study COMPLETED	5	10	4	5
Overall Study NOT COMPLETED	0	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Efavirenz - 600 mg Participants received 600 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz - 1200 mg Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz - 1800 mg Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz - 2200 mg Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity.
Overall Study Protocol Violation	0	1	0	0

Baseline Characteristics

Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Efavirenz: 600 mg n=5 Participants Cohort 1 : Participants received 600 mg of Efavirenz (oral / once a day), until progression or toxicity. Efavirenz 600mg: Efavirenz 600 mg (oral daily intake)	Efavirenz: 1200 mg n=10 Participants Cohort 2 : Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity. Efavirenz 600mg: Efavirenz 1200 mg (oral daily intake)	Efavirenz: 1800 mg n=4 Participants Cohort 3 : Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity. Efavirenz 600mg: Efavirenz 1800 mg (oral daily intake)	Efavirenz: 2200 mg n=5 Participants Cohort 4 : Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity. Efavirenz 600mg: Efavirenz 2200 mg (oral daily intake)	Total n=24 Participants Total of all reporting groups
Age, Continuous	64.4 years n=99 Participants	59.0 years n=107 Participants	66.8 years n=206 Participants	63.4 years n=7 Participants	62.2 years n=31 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants	1 Participants n=7 Participants	9 Participants n=31 Participants
Sex: Female, Male Male	3 Participants n=99 Participants	7 Participants n=107 Participants	1 Participants n=206 Participants	4 Participants n=7 Participants	15 Participants n=31 Participants
Region of Enrollment France	5 participants n=99 Participants	10 participants n=107 Participants	4 participants n=206 Participants	5 participants n=7 Participants	24 participants n=31 Participants

PRIMARY outcome

Timeframe: Up to 28 days for each dosing cohort

Outcome measures

Outcome measures
Measure	All Participants n=25 Participants All participants who received at least 1 dose of Efavirenz, either at 600 mg, 1200 mg, 1800 mg, or 2200 mg.	Efavirenz: 1200 mg Cohort 2 : Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 1800 mg Cohort 3 : Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 2200 mg Cohort 4 : Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity.
Maximum Tolerated Dose (MTD) of Efavirenz	1200 mg	—	—	—

PRIMARY outcome

Timeframe: Up to 28 days for each dosing cohort

A DLT was any drug-related toxicity with grade ≥ 3 according to NCI-CTCAE v4.0 (except alopecia, nausea and vomiting, regardless of grade), any drug-related toxicity, regardless of grade, who led a treatment delay\> 14 days, a score ≥ 19 for the Hospital Anxiety And Depression Scale (HAD) during treatment.

Outcome measures

Outcome measures
Measure	All Participants n=5 Participants All participants who received at least 1 dose of Efavirenz, either at 600 mg, 1200 mg, 1800 mg, or 2200 mg.	Efavirenz: 1200 mg n=10 Participants Cohort 2 : Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 1800 mg n=4 Participants Cohort 3 : Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 2200 mg n=5 Participants Cohort 4 : Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)	0 Participants	3 Participants	1 Participants	3 Participants

SECONDARY outcome

Timeframe: up to 3 months after first adminitration of Efavirenz

Objective response is defined as complete or partial response (CR, PR) using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Objective reponse rate is calculated as the number of patients with objective reponse divided by the number of alive patients.

Outcome measures

Outcome measures
Measure	All Participants n=24 Participants All participants who received at least 1 dose of Efavirenz, either at 600 mg, 1200 mg, 1800 mg, or 2200 mg.	Efavirenz: 1200 mg Cohort 2 : Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 1800 mg Cohort 3 : Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 2200 mg Cohort 4 : Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity.
12-week Objective Response Rate	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Evaluated up to 3 months after first administration of Efavirenz

Non progression is defined as complete or partial response (CR, PR) or stable disease (SD), using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Non-progression rate is calculated as the number of alive and progression free patients divided by the number of patients.

Outcome measures

Outcome measures
Measure	All Participants n=24 Participants All participants who received at least 1 dose of Efavirenz, either at 600 mg, 1200 mg, 1800 mg, or 2200 mg.	Efavirenz: 1200 mg Cohort 2 : Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 1800 mg Cohort 3 : Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 2200 mg Cohort 4 : Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity.
12-week Non-progression Rate	0 Participants	—	—	—

Adverse Events

Efavirenz: 600 mg

Serious events: 3 serious events

Other events: 5 other events

Deaths: 5 deaths

Efavirenz: 1200 mg

Serious events: 4 serious events

Other events: 11 other events

Deaths: 11 deaths

Efavirenz: 1800 mg

Serious events: 4 serious events

Other events: 4 other events

Deaths: 4 deaths

Efavirenz: 2200 mg

Serious events: 3 serious events

Other events: 5 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Efavirenz: 600 mg n=5 participants at risk Cohort 1 : Participants received 600 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 1200 mg n=11 participants at risk Cohort 2 : Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 1800 mg n=4 participants at risk Cohort 3 : Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 2200 mg n=5 participants at risk Cohort 4 : Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity.
Blood and lymphatic system disorders Other	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/11 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Gastrointestinal disorders Other	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	9.1% 1/11 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
General disorders Other	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	18.2% 2/11 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	100.0% 4/4 • Number of events 7 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	40.0% 2/5 • Number of events 3 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Hepatobiliary disorders other	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/11 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Metabolism and nutrition disorders Other	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	9.1% 1/11 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	50.0% 2/4 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Other	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/11 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Nervous system disorders Other	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/11 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Psychiatric disorders Other	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	18.2% 2/11 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	25.0% 1/4 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	20.0% 1/5 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders other	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/11 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.

Other adverse events

Additional Information

Dr Guilhem Roubaud

Institut Bergonié

Phone: 33 5 56 33 33 33

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Efavirenz: 600 mg n=5 participants at risk Cohort 1 : Participants received 600 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 1200 mg n=11 participants at risk Cohort 2 : Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 1800 mg n=4 participants at risk Cohort 3 : Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity.	Efavirenz: 2200 mg n=5 participants at risk Cohort 4 : Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity.
Blood and lymphatic system disorders Not collected	100.0% 1/1 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	18.2% 2/11 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	50.0% 2/4 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Eye disorders Not collected	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/11 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Gastrointestinal disorders Not collected	80.0% 4/5 • Number of events 7 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	72.7% 8/11 • Number of events 12 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	75.0% 3/4 • Number of events 4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	60.0% 3/5 • Number of events 7 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
General disorders Not collected	60.0% 3/5 • Number of events 3 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	72.7% 8/11 • Number of events 11 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	100.0% 4/4 • Number of events 7 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	100.0% 5/5 • Number of events 9 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Hepatobiliary disorders Not collected	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/11 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Infections and infestations Not collected	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	9.1% 1/11 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Injury, poisoning and procedural complications Not collected	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	9.1% 1/11 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Investigations Not collected	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	9.1% 1/11 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	40.0% 2/5 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Metabolism and nutrition disorders Not collected	40.0% 2/5 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	36.4% 4/11 • Number of events 4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	50.0% 2/4 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	40.0% 2/5 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Musculoskeletal and connective tissue disorders Not collected	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	27.3% 3/11 • Number of events 3 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Not collected	20.0% 1/5 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/11 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Nervous system disorders Not collected	40.0% 2/5 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	45.5% 5/11 • Number of events 6 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	80.0% 4/5 • Number of events 5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Psychiatric disorders Not collected	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	54.5% 6/11 • Number of events 8 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	50.0% 2/4 • Number of events 3 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	100.0% 5/5 • Number of events 12 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Not collected	60.0% 3/5 • Number of events 3 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/11 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	25.0% 1/4 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Skin and subcutaneous tissue disorders Not collected	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	9.1% 1/11 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	25.0% 1/4 • Number of events 2 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
Vascular disorders Not collected	80.0% 4/5 • Number of events 4 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	9.1% 1/11 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	25.0% 1/4 • Number of events 1 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.	0.00% 0/5 • Adverse event data were collected until death or date of the end of study (6 months after the inclusion of the last patient) Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.