Phase I Study of Lurbinectedin (PM01183) in Combination W... | NCT01831089

Label	Type	Description	Intervention Names
Treatment	Experimental	PM01183 + paclitaxel +/- bevacizumab	Drug: PM01183 + paclitaxel +/- bevacizumab

Name	Type	Description	Arm Group Labels	Other Names
PM01183 + paclitaxel +/- bevacizumab	Drug	PM01183: 1 mg and 4 mg vials. Powder for concentrate for solution for infusion paclitaxel: 6 mg/ml concentrate for solution for infusion bevacizumab: 25 mg/ml concentrate for solution for infusion Once a recommended dose is defined for the PM01183 and weekly paclitaxel combination, the feasibility of adding bevacizumab to this combination will be explored in a prospectively selected cohort of patients

Measure	Description	Time Frame
Maximum Tolerated Dose (MTD)	The MTD will be the lowest level at which one third or more evaluable patients experience a DLT in Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.	The MTD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)
Recommended Dose (RD)	The RD will be the highest DL explored with less than one third of the patients experiencing a DLT during Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.	The RD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)	DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.	DLT was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)

Measure	Description	Time Frame
Best Tumor Response	Best overall response:Best response recorded from the start of the study treatment until the end of treatment Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to<10 mm Partial Response (PR):At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression) Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum diameters while on study Treatment failure (TF):symptomatic deterioration or death due to progression

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Voluntarily signed and dated written informed consent
Age between 18 and 75 years old (both inclusive)
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1
Life expectancy ≥ 3 months.
Patients with a histologically/cytologically confirmed diagnosis of advanced and/or unresectable disease of any of the following tumors:
1. Breast cancer
2. Epithelial ovarian cancer or gynecological cancer
3. Head and neck squamous cell carcinoma
4. Non-small cell lung cancer
5. Small cell lung cancer
6. Platinum-refractory germ-cell tumors.
7. Adenocarcinoma or carcinoma of unknown primary site
Adequate bone marrow, renal, hepatic, and metabolic function
Recovery to grade ≤ 1 or to baseline from any Adverse Event (AE) derived from previous treatment (excluding alopecia of any grade).
Pre-menopausal women must have a negative pregnancy test before study entry and agree to use a medically acceptable method of contraception throughout the treatment period and for at least six weeks after treatment discontinuation

Exclusion Criteria:

Prior treatment with PM01183 or weekly paclitaxel or nanoalbumin-paclitaxel
Patients who have previously discontinued paclitaxel-based regimes due to drug related toxicity.
Known hypersensitivity to bevacizumab or any component of its formulation
Patients who have previously discontinued bevacizumab-containing regimes due to drug-related toxicity.
More than three prior lines of chemotherapy
Less than three months since last taxane-containing therapy.
Wash-out period:
1. Less than three weeks since the last chemotherapy-containing regimen
2. Less than three weeks since the last radiotherapy dose
3. Less than four weeks since last monoclonal antibody-containing therapy
Concomitant diseases/conditions:

Unstable angina, myocardial infarction, valvular heart disease, encephalopathy, ischemic attacks, hemorrhagic or ischemic cerebrovascular accident (CVA) or ongoing pulmonary embolism within last year, arrhythmia, hepatopathy, uncontrolled infection, hemoptysis or oxygen requiring dyspnea, known HIV infection, bleeding risk, muscular problems, peripheral neuropathy, Symptomatic or progressive brain metastases or leptomeningeal disease.

Men or pre-menopausal women who are not using an effective method of contraception as previously described; actively breast feeding women.
Patients who have pelvic irradiation with doses ≥ 45 Grays (Gy).
History of previous bone marrow and/or stem cell transplantation.
Confirmed bone marrow involvement

ID	Title	Description
FG000	Paclitaxel [60.0 mg/m2] / PM01183 [3.0 mg FD]	Cohort I Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 3.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.

Arm/Group Information

ID	Title	Description
BG000	Paclitaxel [60.0 mg/m2] / PM01183 [3.0 mg FD]	Cohort I Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 3.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.
BG001	Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD]	Cohort II Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 4.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.
BG002	Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD	Cohort III Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 5.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.
BG003	Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD]	Cohort IV Paclitaxel 80.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 5.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.
BG004	Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD]	Cohort V Paclitaxel 80.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 4.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.
BG005	Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg	All three study medications were administered via a central or a peripheral venous catheter through a pump device, as follows: Paclitaxel 80.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour. PM01183 as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour. Bevacizumab (BEV) 15 mg/kg as an i.v. infusion on Day 1 q3wk, immediately after paclitaxel and PM01183 infusions, Minimum duration of infusion was 90 minutes for the first dose and, if well tolerated, 60 minutes for the second dose and 30 minutes for all subsequent doses. nous catheter was used) through a pump device. Patients in this group were to receive paclitaxel, PM01183 and BEV for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, both PM01183 and BEV could be continued until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.
BG006	Total	Total of all reporting groups

Units	Counts
Participants	BG0003 BG0013 BG0026 BG0036 BG00437 BG00514 BG00669

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Tolerated Dose (MTD)

The MTD will be the lowest level at which one third or more evaluable patients experience a DLT in Cycle 1.

DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.

Three patients at the RD were not evaluable because they did not receive a complete Cycle 1 due to disease-related grade 3 vomiting and early PD, disease-related grade 3 confusional state, and because not enough information for DLT evaluation was collected during Cycle 1.

Posted

Number

mg/m2 / mg FD

The MTD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)

ID	Title	Description
OG000	Group A (Paclitaxel/PM01183)	All participants who received at least 1 dose of Paclitaxel/PM01183, either at 60/3.0, 60/4.0, 60/5.0, 80/5.0, 80/4.0 mg/m2 / mg FD.

Units	Counts
Participants	OG00052

Title

Denominators

Categories

Title	Measurements
	OG000NAPaclitaxel \[80.0 mg/m2\] / PM01183 \[5.0 mg FD\]

Primary

Recommended Dose (RD)

The RD will be the highest DL explored with less than one third of the patients experiencing a DLT during Cycle 1.

DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.

Posted

Number

mg/m2 / mg FD

The RD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)

ID	Title	Description
OG000	Group A (Paclitaxel/PM01183)	All participants who received at least 1 dose of Paclitaxel/PM01183, either at 60/3.0, 60/4.0, 60/5.0, 80/5.0, 80/4.0 mg/m2 / mg FD.

Units	Counts
Participants	OG000

Primary

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.

Posted

Count of Participants

Participants

DLT was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)

ID	Title	Description
OG000	Paclitaxel [60.0 mg/m2] / PM01183 [3.0 mg FD]	Cohort I Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 3.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.
OG001	Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD]	Cohort II Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 4.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.

Secondary

Best Tumor Response

Best overall response:Best response recorded from the start of the study treatment until the end of treatment Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to<10 mm Partial Response (PR):At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression) Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum diameters while on study Treatment failure (TF):symptomatic deterioration or death due to progression

Posted

Count of Participants

Participants

Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)

ID	Title	Description
OG000	Paclitaxel [60.0 mg/m2] / PM01183 [3.0 mg FD]	Cohort I Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 3.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.

Secondary

Progression-free Survival

Progression-free survival (PFS) was defined as the time from the date of first infusion of study treatment to the date of progression or death (due to any cause). If progression or death had not occurred at the time of the analysis, the PFS was censored.

Posted

Median

95% Confidence Interval

months

Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)

ID	Title	Description
OG000	Paclitaxel [60.0 mg/m2] / PM01183 [3.0 mg FD]	Cohort I Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 3.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.
OG001	Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD]	Cohort II Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 4.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.

Secondary

Duration of Response (DR)

Duration of response (DR) was defined as the time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented

In cohort II, no patients with PR or CR.

Posted

Median

95% Confidence Interval

months

Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)

ID	Title	Description
OG000	Paclitaxel [60.0 mg/m2] / PM01183 [3.0 mg FD]	Cohort I Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 3.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.
OG001	Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD]	Cohort II Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 4.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.

Secondary

Quality of Life (QoL)

Change from baseline to last cycle. European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL scale scores.

The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC QLQ-C30 (version 3.0) developed for palliative care. Wilcoxon signed ranks test repeat-measure analyses of variance were used to measure the change value from baseline value. Data has to be analysed following the corresponding EORTC manual http://www.eortc.be/qol/files/SCManualQLQ-C15-PAL.pdf and the overall quality of life assessment is contained in 0 to 100 where a higher value represents a better state.

Posted

Mean

Standard Deviation

score on a scale

Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)

ID	Title	Description
OG000	Paclitaxel [60.0 mg/m2] / PM01183 [3.0 mg FD]	Cohort I Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 3.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.
OG001

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Paclitaxel [60.0 mg/m2] / PM01183 [3.0 mg FD]	Cohort I Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 3.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.	0	3	0	3	3	3
EG001	Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD]	Cohort II Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 4.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.	0	3	0	3	3	3
EG002	Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD	Cohort III Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 5.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.	0	6	3	6	6	6
EG003	Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD]	Cohort IV Paclitaxel 80.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 5.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.	0	6	2	6	6	6
EG004	Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD]	Cohort V Paclitaxel 80.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter. PM01183 4.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device. Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.	3	37	15	37	36	37
EG005	Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg	All three study medications were administered via a central or a peripheral venous catheter through a pump device, as follows: Paclitaxel 80.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour. PM01183 as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour. Bevacizumab (BEV) 15 mg/kg as an i.v. infusion on Day 1 q3wk, immediately after paclitaxel and PM01183 infusions, Minimum duration of infusion was 90 minutes for the first dose and, if well tolerated, 60 minutes for the second dose and 30 minutes for all subsequent doses. nous catheter was used) through a pump device. Patients in this group were to receive paclitaxel, PM01183 and BEV for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, both PM01183 and BEV could be continued until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement.	2	14	7	14	12	14

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Venous thrombosis	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG0030 events0 affected6 at risk EG0044 events1 affected37 at risk EG0050 events0 affected14 at risk
Tumor associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Pain	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Pyrexia	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Chest pain	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Confusional state	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected6 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Retinal detachment	Eye disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected6 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Large intestine perforation	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Gallbladder obstruction	Hepatobiliary disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Catheter site cellulitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Pneumonia pneumococcal	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Sepsis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Abdominal abscess	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertension	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0028 events2 affected6 at risk EG0031 events1 affected6 at risk EG0046 events2 affected37 at risk EG00513 events3 affected14 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0013 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Chest pain	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Extravasation	General disorders	MedDRA (16.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Fatigue	General disorders	MedDRA (16.0)	Systematic Assessment	EG00011 events2 affected3 at risk EG00123 events3 affected3 at risk EG00242 events6 affected6 at risk EG003
Influenza like illness	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Oedema peripheral	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Pain	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0025 events2 affected6 at risk EG003
Pyrexia	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0015 events2 affected3 at risk EG0021 events1 affected6 at risk EG003
Injection site erythema	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected6 at risk EG003
Depression	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment	EG0007 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected6 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0025 events1 affected6 at risk EG003
Weight decreased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0002 events1 affected3 at risk EG0011 events1 affected3 at risk EG00220 events4 affected6 at risk EG003
Weight increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0028 events1 affected6 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0023 events1 affected6 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0024 events2 affected6 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0023 events1 affected6 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0002 events1 affected3 at risk EG0010 events0 affected3 at risk EG0029 events3 affected6 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0019 events1 affected3 at risk EG00217 events4 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0002 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Headache	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0021 events1 affected6 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG00212 events2 affected6 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected6 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Dry eye	Eye disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Vision blurred	Eye disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0014 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Aphthous stomatitis	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0021 events1 affected6 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected6 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0003 events2 affected3 at risk EG0012 events2 affected3 at risk EG0026 events2 affected6 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected6 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0023 events1 affected6 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0021 events1 affected6 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0004 events2 affected3 at risk EG0015 events2 affected3 at risk EG0029 events2 affected6 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG00210 events1 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0012 events1 affected3 at risk EG0025 events2 affected6 at risk EG003
Colonic fistula	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Gastrointestinal fistula	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0003 events1 affected3 at risk EG0012 events1 affected3 at risk EG0026 events1 affected6 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0021 events1 affected6 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Fistula	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypertrophic osteoarthropathy	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0002 events1 affected3 at risk EG0010 events0 affected3 at risk EG0026 events2 affected6 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0021 events1 affected6 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Abdominal abscess	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Abdominal infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Septic shock	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Tooth abscess	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Subileus	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0013 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Enteritis	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected6 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Mucosal inflammation	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0023 events1 affected6 at risk EG003
Oedema	General disorders	MedDRA (16.0)	Systematic Assessment	EG0004 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Catheter site inflammation	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Chills	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Face oedema	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Infusion site thrombosis	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Thrombosis in device	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Infusion site phlebitis	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Malaise	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0024 events1 affected6 at risk EG003
Lung infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Pneumonia	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Enterococcal infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Herpes zoster	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0023 events1 affected6 at risk EG003
Influenza	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Nail infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected6 at risk EG003
Pharyngitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Oral herpes	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Cellulitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Blood cholesterol increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0002 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected6 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0002 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Memory impairment	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Presyncope	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Somnolence	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Agitation	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0028 events1 affected6 at risk EG003
Rhonchi	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0026 events1 affected6 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Dermatitis acneiform	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Jugular vein thrombosis	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0014 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Palpitations	Cardiac disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0023 events1 affected6 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Urinary tract pain	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected6 at risk EG003
Thrombosis	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Photophobia	Eye disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Dysaesthesia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		New York	New York		United States

ID	Term
D001943	Breast Neoplasms
D010051	Ovarian Neoplasms
D002289	Carcinoma, Non-Small-Cell Lung
D055752	Small Cell Lung Carcinoma

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D004701	Endocrine Gland Neoplasms
D010049	Ovarian Diseases
D000291	Adnexal Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D005833	Genital Neoplasms, Female
D014565	Urogenital Neoplasms
D000091662	Genital Diseases
D004700	Endocrine System Diseases
D006058	Gonadal Disorders
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases