Trial Outcomes & Findings for Clinical Trial of PM00104 (Zalypsis®) in Patients With Advanced and/or Metastatic Endometrial or Cervical Cancer Previously Treated With One Line of Systemic Chemotherapy (NCT NCT00900562)

Last Updated: 2021-10-28

Results Overview

Overall Response Rate defined as the percentage of patients with either complete response (CR) or partial response (PR) according to RECIST v.1.0. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; RECIST, Response Evaluation Criteria in Solid Tumors

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

At baseline and every other cycle (± 1 week) until evidence of PD, up to 2 years

Results posted on

2021-10-28

Participant Flow

Endometrial Cancer: 12 patients were recruited and treated at 4 sites in the US. Patients participated between 14/08/2009 (first consent signed (CS)) and 22/2/2010 (last CS). The first dose was administered on 26/08/2009 and the last dose on 2/4/2010. Cervical Cancer: 7 patients were recruited and treated at 3 sites in the US. Patients participated in the study between 19/8/2009 (first CS) and 22/12/2010 (last CS). The first dose was administered on 26/10/2009 and the last dose on 10/03/2011

Participant milestones

Participant milestones
Measure	Endometrial Cancer Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
Overall Study STARTED	12	7
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	12	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Endometrial Cancer Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
Overall Study Progressive disease	9	5
Overall Study Toxicity	1	0
Overall Study Death	1	1
Overall Study Withdrawal by Subject	0	1
Overall Study Unrelated adverse event	1	0

Baseline Characteristics

Clinical Trial of PM00104 (Zalypsis®) in Patients With Advanced and/or Metastatic Endometrial or Cervical Cancer Previously Treated With One Line of Systemic Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Endometrial Cancer n=12 Participants Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer n=7 Participants Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Total n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Age, Continuous	61.5 years n=5 Participants	38 years n=7 Participants	59 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	7 participants n=7 Participants	19 participants n=5 Participants
Eastern Cooperative Oncology Group Performance Status 0	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Eastern Cooperative Oncology Group Performance Status 1	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Histology Adenocarcinoma	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Histology Adenosquamous	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Histology Clear cell	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Histology Endometrioid	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Histology Mixed	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Histology Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Histology Papillary serous	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Histology Squamous cell carcinoma	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Extent of disease Metastatic	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Extent of disease Locally advanced	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Histology grade Poorly differentiated	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Histology grade Moderately differentiated	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Histology grade Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sites involved 1	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Sites involved 2	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sites involved 3	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sites involved >3	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Time from diagnosis to first infusion	18.2 months n=5 Participants	10.7 months n=7 Participants	16.6 months n=5 Participants
Time from last progression to first infusion	0.9 months n=5 Participants	0.8 months n=7 Participants	0.8 months n=5 Participants
Prior Surgery	11 Participants n=5 Participants	6 Participants n=7 Participants	17 Participants n=5 Participants
Prior Systemic anticancer therapy	12 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: At baseline and every other cycle (± 1 week) until evidence of PD, up to 2 years

Population: Two patients were not evaluable for efficacy: One patient received only one PM00104 infusion in Cycle 1 and had to be withdrawn from the study due to a troponin I increase, which occurred seven days after the first infusion of PM00104 and was considered serious (SAE) and related to PM00104; One patient only received one PM00104 infusion and was withdrawn from the study due to drug-unrelated marantic endocarditis

Outcome measures

Outcome measures
Measure	Endometrial Cancer n=10 Participants Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer n=7 Participants Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
Overall Response Rate (ORR)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At baseline and every other cycle (± 1 week) until evidence of PD, up to 2 years

Best tumor response was defined as the best response achieved during the study according to RECIST v1.0 CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; RECIST, Response Evaluation Criteria in Solid Tumors

Outcome measures

Outcome measures
Measure	Endometrial Cancer n=10 Participants Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer n=7 Participants Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
Best Tumor Response SD ≥ 4 months	1 Participants	0 Participants
Best Tumor Response PD	9 Participants	7 Participants

SECONDARY outcome

Timeframe: From the date of first infusion of study treatment to the date of progression or death, up to 2 years

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, PFS was censored on the date of last tumor evaluation. PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density

Outcome measures

Outcome measures
Measure	Endometrial Cancer n=10 Participants Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer n=7 Participants Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
Progression Free Survival	1.8 months Interval 1.7 to 2.0	1.5 months Interval 1.5 to 1.8

SECONDARY outcome

Timeframe: At 4 months

Progression-free survival rate at 4 months was defined as the percentage of patients who did not progress and were alive at 4 months. PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density

Outcome measures

Outcome measures
Measure	Endometrial Cancer n=10 Participants Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer n=7 Participants Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
Progression Free Survival Rate at 4 Months	10 percentage of participants Interval 0.0 to 28.6	0 percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: From the date of first infusion to the date of death, up to 2 years

Overall survival (OS) was defined as the time from the date of first infusion of study treatment to the date of death (due to any cause). Patients with no documented death were censored at the last date they were known to be alive

Outcome measures

Outcome measures
Measure	Endometrial Cancer n=10 Participants Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer n=7 Participants Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
Overall Survival	5.5 months Interval 4.8 to 11.5	5.6 months Insufficient number of participants with events

SECONDARY outcome

Timeframe: 0 (Pre-infusion) and 1, 1.5, 3, 7, 24, 48, 168 hours after the end of first infusion (Day 1)

Population: All treated patients

Cmax Maximum plasma concentration, directly determined from the experimental data

Outcome measures

Outcome measures
Measure	Endometrial Cancer n=19 Participants Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
PM00104 Plasma PK Parameters (Cmax) at First Infusion	26.47 μg/l Standard Deviation 11.98	—

SECONDARY outcome

Timeframe: 0 (Pre-infusion) and 1, 1.5, 3, 7, 24, 48, 168 hours after the end of first infusion (Day 1)

Population: All treated patients

AUC Area under the plasma concentration-time curve from time zero to infinity.

Outcome measures

Outcome measures
Measure	Endometrial Cancer n=19 Participants Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
PM00104 Plasma PK Parameters (AUC) at First Infusion	80.88 h*μg/l Standard Deviation 37.41	—

SECONDARY outcome

Timeframe: 0 (Pre-infusion) and 1, 1.5, 3, 7, 24, 48, 168 hours after the end of second infusion (Day 8)

Population: All treated patients with second infusion

Cmax Maximum plasma concentration, directly determined from the experimental data

Outcome measures

Outcome measures
Measure	Endometrial Cancer n=16 Participants Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
PM00104 Plasma PK Parameters (Cmax) at Second Infusion	35.02 μg/l Standard Deviation 21.06	—

SECONDARY outcome

Timeframe: 0 (Pre-infusion) and 1, 1.5, 3, 7, 24, 48, 168 hours after the end of second infusion (Day 8)

Population: All treated patients with Second infusion

AUC Area under the plasma concentration-time curve from time zero to infinity

Outcome measures

Outcome measures
Measure	Endometrial Cancer n=16 Participants Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
PM00104 Plasma PK Parameters (AUC) at Second Infusion	86.55 h*μg/l Standard Deviation 40.41	—

Adverse Events

Endometrial Cancer

Serious events: 5 serious events

Other events: 12 other events

Deaths: 9 deaths

Cervical Cancer

Serious events: 3 serious events

Other events: 7 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Developtment, Department of PharmaMar´s Oncology., Business Unit.

Pharma Mar S.A.

Phone: 0034 91846 60 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review.
Publication restrictions are in place

Restriction type: OTHER

Measure	Endometrial Cancer n=12 participants at risk Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer n=7 participants at risk Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
Blood and lymphatic system disorders Disseminated intravascular coagulation	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Cardiac disorders Endocarditis noninfective	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Diarrhoea	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Nausea	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Vomiting	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
General disorders Pyrexia	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Infections and infestations Escherichia bacteraemia	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Investigations Troponin I increased	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Metabolism and nutrition disorders Anorexia	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Metabolism and nutrition disorders Dehydration	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Nervous system disorders Cerebral ischaemia	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Renal and urinary disorders Hydronephrosis	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Respiratory, thoracic and mediastinal disorders Atelectasis	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Respiratory, thoracic and mediastinal disorders Pleural effusion	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Respiratory, thoracic and mediastinal disorders Productive cough	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Vascular disorders Deep vein thrombosis	16.7% 2/12 • Number of events 3 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Vascular disorders Hypotension	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Blood and lymphatic system disorders Anaemia	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Abdominal pain	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 3 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Constipation	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 2 • From first infusion to study termination, up to 2 years
Infections and infestations Enterobacter infection	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Infections and infestations Pneumonia	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Investigations Blood creatinine increased	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Renal and urinary disorders Renal failure	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years

Measure	Endometrial Cancer n=12 participants at risk Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials	Cervical Cancer n=7 participants at risk Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks. Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials
Blood and lymphatic system disorders Anaemia	16.7% 2/12 • Number of events 3 • From first infusion to study termination, up to 2 years	57.1% 4/7 • Number of events 9 • From first infusion to study termination, up to 2 years
Blood and lymphatic system disorders Thrombocytopenia	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Cardiac disorders Cardio-respiratory arrest	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Cardiac disorders Sinus tachycardia	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Cardiac disorders Tachycardia	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Cardiac disorders Ventricular tachycardia	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Ear and labyrinth disorders Ear pain	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Ear and labyrinth disorders Tinnitus	16.7% 2/12 • Number of events 3 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Eye disorders Vision blurred	16.7% 2/12 • Number of events 3 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Eye disorders Visual disturbance	16.7% 2/12 • Number of events 3 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Abdominal distension	16.7% 2/12 • Number of events 2 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Abdominal pain	16.7% 2/12 • Number of events 3 • From first infusion to study termination, up to 2 years	28.6% 2/7 • Number of events 3 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Constipation	58.3% 7/12 • Number of events 13 • From first infusion to study termination, up to 2 years	71.4% 5/7 • Number of events 13 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Diarrhoea	41.7% 5/12 • Number of events 5 • From first infusion to study termination, up to 2 years	28.6% 2/7 • Number of events 2 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Dyspepsia	25.0% 3/12 • Number of events 3 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Dysphagia	8.3% 1/12 • Number of events 2 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Gastritis	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Mouth ulceration	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Nausea	58.3% 7/12 • Number of events 16 • From first infusion to study termination, up to 2 years	57.1% 4/7 • Number of events 6 • From first infusion to study termination, up to 2 years
Gastrointestinal disorders Vomiting	25.0% 3/12 • Number of events 3 • From first infusion to study termination, up to 2 years	57.1% 4/7 • Number of events 6 • From first infusion to study termination, up to 2 years
General disorders Asthenia	16.7% 2/12 • Number of events 4 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
General disorders Chest pain	16.7% 2/12 • Number of events 2 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
General disorders Chills	25.0% 3/12 • Number of events 4 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
General disorders Fatigue	58.3% 7/12 • Number of events 15 • From first infusion to study termination, up to 2 years	85.7% 6/7 • Number of events 12 • From first infusion to study termination, up to 2 years
General disorders Generalised oedema	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
General disorders Mucosal inflammation	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
General disorders Oedema	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
General disorders Oedema peripheral	16.7% 2/12 • Number of events 3 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
General disorders Pain	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
General disorders Pyrexia	33.3% 4/12 • Number of events 4 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Infections and infestations Catheter related infection	0.00% 0/12 • From first infusion to study termination, up to 2 years	28.6% 2/7 • Number of events 2 • From first infusion to study termination, up to 2 years
Infections and infestations Fungal infection	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Infections and infestations Sepsis syndrome	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Infections and infestations Urinary tract infection	25.0% 3/12 • Number of events 3 • From first infusion to study termination, up to 2 years	28.6% 2/7 • Number of events 2 • From first infusion to study termination, up to 2 years
Injury, poisoning and procedural complications Fall	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Investigations Alanine aminotransferase increased	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Investigations Aspartate aminotransferase increased	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Investigations Neutrophil count decreased	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Investigations Weight decreased	16.7% 2/12 • Number of events 2 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Metabolism and nutrition disorders Anorexia	41.7% 5/12 • Number of events 8 • From first infusion to study termination, up to 2 years	42.9% 3/7 • Number of events 5 • From first infusion to study termination, up to 2 years
Metabolism and nutrition disorders Decreased appetite	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Metabolism and nutrition disorders Dehydration	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/12 • From first infusion to study termination, up to 2 years	28.6% 2/7 • Number of events 4 • From first infusion to study termination, up to 2 years
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 2/12 • Number of events 2 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Musculoskeletal and connective tissue disorders Bone pain	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 3 • From first infusion to study termination, up to 2 years
Musculoskeletal and connective tissue disorders Myalgia	16.7% 2/12 • Number of events 2 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 2 • From first infusion to study termination, up to 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	16.7% 2/12 • Number of events 5 • From first infusion to study termination, up to 2 years	28.6% 2/7 • Number of events 3 • From first infusion to study termination, up to 2 years
Nervous system disorders Cerebrovascular accident	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Nervous system disorders Dizziness	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Nervous system disorders Dysgeusia	8.3% 1/12 • Number of events 2 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Nervous system disorders Headache	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Nervous system disorders Hypoaesthesia	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Nervous system disorders Memory impairment	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Nervous system disorders Neuropathy peripheral	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Nervous system disorders Paraesthesia	8.3% 1/12 • Number of events 2 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Nervous system disorders Peripheral sensory neuropathy	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Psychiatric disorders Depression	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Psychiatric disorders Insomnia	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Psychiatric disorders Mental disorder	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Psychiatric disorders Mood altered	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Renal and urinary disorders Dysuria	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Renal and urinary disorders Haematuria	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Renal and urinary disorders Pollakiuria	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Renal and urinary disorders Urinary retention	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Reproductive system and breast disorders Vaginal discharge	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Reproductive system and breast disorders Vaginal haemorrhage	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	28.6% 2/7 • Number of events 4 • From first infusion to study termination, up to 2 years
Respiratory, thoracic and mediastinal disorders Cough	16.7% 2/12 • Number of events 2 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Respiratory, thoracic and mediastinal disorders Dyspnoea	41.7% 5/12 • Number of events 5 • From first infusion to study termination, up to 2 years	28.6% 2/7 • Number of events 2 • From first infusion to study termination, up to 2 years
Respiratory, thoracic and mediastinal disorders Epistaxis	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Respiratory, thoracic and mediastinal disorders Hiccups	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Respiratory, thoracic and mediastinal disorders Pleural effusion	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Skin and subcutaneous tissue disorders Alopecia	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Skin and subcutaneous tissue disorders Night sweats	25.0% 3/12 • Number of events 3 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Vascular disorders Deep vein thrombosis	0.00% 0/12 • From first infusion to study termination, up to 2 years	14.3% 1/7 • Number of events 1 • From first infusion to study termination, up to 2 years
Vascular disorders Jugular vein thrombosis	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years
Vascular disorders Vena cava thrombosis	8.3% 1/12 • Number of events 1 • From first infusion to study termination, up to 2 years	0.00% 0/7 • From first infusion to study termination, up to 2 years