Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM060184 in Combination With Gemcitabine in Selected Patients With Advanced Solid Tumors
Sponsor
PharmaMar (Industry)
Overall Status
Completed
CT.gov ID
NCT02533674
Collaborator
(none)
57
2
1
54.9
28.5
0.5
Study Details
Study Description
Brief Summary
Prospective, open-label, dose-ranging, uncontrolled phase I study with escalating doses of PM060184 in combination with gemcitabine in selected patients with advanced solid tumors.
The study objectives are:
To determine the MTD and the RD of PM060184 in combination with gemcitabine in selected patients with advanced solid tumors.
To characterize the safety profile and feasibility of this combination in this study population.
To characterize the pharmacokinetics of this combination and to detect major drug-drug PK interactions.
To obtain preliminary information on the clinical antitumor activity of this combination.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
57 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM060184 in Combination With Gemcitabine in Selected Patients With Advanced Solid Tumors
Actual Study Start Date
:
Dec 12, 2014
Actual Primary Completion Date
:
Jul 11, 2019
Actual Study Completion Date
:
Jul 11, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: gemcitabine plus PM060184
|
Drug: Gemcitabine plus PM060184
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose Limiting Toxicities [From the start of treatment to the end of cycle one which are 3 weeks]
Dose-limiting toxicities were defined as: Grade 4 neutropenia lasting >3 days Grade≥3 febrile neutropenia of any duration or neutropenic sepsis Grade 4 thrombocytopenia or grade 3 with any major bleeding episode requiring a platelet transfusion Grade 4 ALT/AST increase, or grade 3 lasting >7 days Treatment-related grade≥2 ALT/AST increase concomitantly with ≥2 x ULN total bilirubin increase and normal AP Any other grade≥3 non-hematological AE that was suspected to be related to study drugs, except nausea/vomiting, hypersensitivity reactions, extravasations, grade 3 asthenia lasting less than one week, anorexia, and non-clinically relevant isolated biochemical abnormalities Delay in the administration of Cycle 2 of the combination exceeding seven (+1) days of the treatment due date due to any AEs related to study drugs. The following circumstances were to be discussed between the Principal Investigator and the Sponsor, and the final consensus had to be documented
Secondary Outcome Measures
- Number of Participants With Clinical Benefit [Every two cycles (every six weeks ± one week) until Cycle 4, and then every three cycles (every nine weeks ± one week) while on treatment, up to 2 years]
Clinical benefit defined as any response or stable disease ≥4 months. 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 (this includes the baseline sum if that is the smallest 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Voluntarily signed and dated written informed consent prior to any specific study procedure.
-
Age ≥ 18 years.
-
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1 (see APPENDIX 1).
-
Life expectancy ≥ 3 months.
-
Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors that progressed to standard therapy or for whom no standard therapy exists:
-
Breast cancer non-candidate for hormone therapy alone.
-
Epithelial ovarian cancer (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas).
-
Locally advanced or metastatic head and neck cancer.
-
Non-small cell lung cancer (NSCLC).
-
Germ cell tumors (GCTs).
-
Biliary tract adenocarcinoma.
-
Adenocarcinoma or carcinoma of unknown primary site (UKPS).
-
Cervix carcinoma.
-
Gastrointestinal stromal tumor (GIST).
-
Urothelial cancer.
- Expansion cohort at the RD:
All patients must have:
-
Measurable disease according to RECIST v.1.1 (or Choi criteria and/or EORTC metabolic response criteria for solid tumors, in the case of GIST); or
-
Evaluable disease by serum markers in the case of ovarian cancer [Gynecologic Cancer Intergroup (GCIG) specific criteria]; and
-
Documented disease progression during or immediately after last therapy according to any of the aforementioned criteria.
-
Wash-out periods: at least three weeks since the last anticancer therapy, including radiation therapy (RT) in more than 35% of the bone marrow; at least three weeks since the last biological/investigational therapy [excluding monoclonal antibodies (MAbs)]; at least four weeks since the last MAb-containing therapy; and at least six weeks since nitrosoureas and mitomycin C (systemic). In the case of hormonesensitive breast cancer progressing while on hormone therapy, the latter must be either stopped up to one week before or continued without changes during the trial.
-
Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ 7 days before inclusion in the study):
-
Platelet count ≥ 100 x 109/l, hemoglobin ≥ 9.0 g/dl and ANC ≥ 1.0 x 109/l.
-
AST and ALT ≤ 3.0 x ULN, independently of the presence of liver metastases.
-
AP ≤ 2.5 x ULN (≤ 5 x ULN if disease-related).
-
Total bilirubin ≤ 1.5 x ULN.
-
International Normalized Ratio (INR) < 1.5 (except if patient is on oral anticoagulation therapy).
-
Calculated creatinine clearance (CrCl) ≥ 50 ml/minute (using Cockcroft and Gault's formula; see APPENDIX 2).
-
Albumin ≥ 2.5 g/dl.
-
Recovery to grade ≤ 1 from any AE derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or asthenia).
-
Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiplegated acquisition (MUGA) within normal range (according to institutional standards).
-
Women of childbearing potential must have a negative serum or urine pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six weeks after discontinuation of treatment. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and/or double barrier.
Exclusion Criteria:
- Concomitant diseases/conditions:
-
History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
-
Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
-
Known chronic active hepatitis or cirrhosis
-
Active uncontrolled infection [i.e., antibiotic, antifungal or antiviral intervention indicated or surgical procedure (i.e., pleural or deep abscess drainage) conducted within 15 days prior to inclusion].
-
Known human immunodeficiency virus (HIV) infection.
-
Current or prior history of grade ≥ 2 peripheral sensory and/or motor neuropathy.
-
Prior treatment with oxaliplatin.
-
Limitation of the patient's ability to comply with the treatment or follow-up protocol.
-
Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
-
Symptomatic, progressive or corticosteroids-requiring documented brain metastases or leptomeningeal disease involvement.
-
Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding.
-
Patients who have had RT in more than 35% of the bone marrow.
-
Treatment with any investigational product within 30 days before the first infusion.
-
Prior treatment with PM060184.
-
Prior treatment with gemcitabine-containing therapy for advanced disease (adjuvant therapy is allowed, provided not more than six cycles were administered and relapse occurred more than six months after the last drug administration), and/or:
- Patients who have previously discontinued gemcitabine-containing regimens due to gemcitabine-related toxicity.
- Known hypersensitivity to gemcitabine or any component of the formulation.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New York | New York | United States | 10461 | |
| 2 | Madrid | Spain |
Sponsors and Collaborators
- PharmaMar
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
PharmaMar
ClinicalTrials.gov Identifier:
NCT02533674
Other Study ID Numbers:
- PM60184-A-003-14
- PM60184-A-003-14
- 2014-002943-16
First Posted:
Aug 27, 2015
Last Update Posted:
Jun 11, 2021
Last Verified:
May 1, 2021
Study Results
Participant Flow
| Recruitment Details | A total of 57 patients were enrolled at three investigational sites, and 55 patients were treated with the GEM/PM060184 combination. Two patients were never treated. Patients participated in this trial between 12 December 2014 and 11 July 2019 (last follow-up). The first dose of the first cycle was given on 10 February 2015 and the last dose of the last cycle was given on 7 June 2019. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | GEM/PM060184 Dose Level I | GEM/PM060184 Dose Level II | GEM/PM060184 Dose Level III | GEM/PM060184 Dose Level IV | GEM/PM060184 Dose Level V | GEM/PM060184 Dose Level VI | GEM/PM060184 Dose Level VII | GEM/PM060184 Dose Level VIII |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level I: 800 mg/m^2 GEM / 6.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level II: 800 mg/m^2 GEM / 7.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level III: 1000 mg/m^2 GEM / 6.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level IV: 1000 mg/m^2 GEM / 8.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level V: 1000 mg/m^2 GEM / 9.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VI: 1000 mg/m^2 GEM / 9.3 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VII:1000 mg/m^2 GEM / 10.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VIII:1000 mg/m^2 GEM / 10.5 mg/m^2 PM060184 |
| Period Title: Dose Level I | ||||||||
| STARTED | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Dose Level I | ||||||||
| STARTED | 0 | 7 | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 7 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Dose Level I | ||||||||
| STARTED | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Dose Level I | ||||||||
| STARTED | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 |
| Period Title: Dose Level I | ||||||||
| STARTED | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 |
| Period Title: Dose Level I | ||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 9 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 9 | 0 | 0 |
| Period Title: Dose Level I | ||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 16 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 16 | 0 |
| Period Title: Dose Level I | ||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
Baseline Characteristics
| Arm/Group Title | GEM/PM060184 Dose Level I | GEM/PM060184 Dose Level II | GEM/PM060184 Dose Level III | GEM/PM060184 Dose Level IV | GEM/PM060184 Dose Level V | GEM/PM060184 Dose Level VI | GEM/PM060184 Dose Level VII | GEM/PM060184 Dose Level VIII | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level I: 800 mg/m^2 GEM / 6.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level II: 800 mg/m^2 GEM / 7.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level III: 1000 mg/m^2 GEM / 6.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level IV: 1000 mg/m^2 GEM / 8.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level V: 1000 mg/m^2 GEM / 9.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VI: 1000 mg/m^2 GEM / 9.3 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VII:1000 mg/m^2 GEM / 10.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VIII:1000 mg/m^2 GEM / 10.5 mg/m^2 PM060184 | Total of all reporting groups |
| Overall Participants | 5 | 7 | 4 | 5 | 5 | 9 | 16 | 6 | 57 |
| Age (years) [Median (Full Range) ] | |||||||||
| Median (Full Range) [years] |
56.0
|
67.0
|
58.5
|
65.0
|
68.0
|
62.0
|
59.0
|
49.0
|
62.0
|
| Age, Customized (Count of Participants) | |||||||||
| 18-55 |
2
40%
|
2
28.6%
|
2
50%
|
0
0%
|
1
20%
|
3
33.3%
|
4
25%
|
5
83.3%
|
19
33.3%
|
| 56-75 |
3
60%
|
5
71.4%
|
2
50%
|
5
100%
|
3
60%
|
5
55.6%
|
11
68.8%
|
1
16.7%
|
35
61.4%
|
| >75 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
1
11.1%
|
1
6.3%
|
0
0%
|
3
5.3%
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
1
20%
|
4
57.1%
|
2
50%
|
5
100%
|
4
80%
|
6
66.7%
|
15
93.8%
|
5
83.3%
|
42
73.7%
|
| Male |
4
80%
|
3
42.9%
|
2
50%
|
0
0%
|
1
20%
|
3
33.3%
|
1
6.3%
|
1
16.7%
|
15
26.3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||||
| White |
4
80%
|
4
57.1%
|
1
25%
|
2
40%
|
3
60%
|
5
55.6%
|
5
31.3%
|
2
33.3%
|
26
45.6%
|
| Black or African American |
0
0%
|
2
28.6%
|
0
0%
|
0
0%
|
2
40%
|
2
22.2%
|
5
31.3%
|
1
16.7%
|
12
21.1%
|
| Asian |
1
20%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Hispanic/Latino |
0
0%
|
1
14.3%
|
3
75%
|
3
60%
|
0
0%
|
2
22.2%
|
5
31.3%
|
2
33.3%
|
16
28.1%
|
| Not provided/not available |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
6.3%
|
1
16.7%
|
2
3.5%
|
| Region of Enrollment (participants) [Number] | |||||||||
| United States |
1
20%
|
4
57.1%
|
3
75%
|
4
80%
|
3
60%
|
5
55.6%
|
12
75%
|
4
66.7%
|
36
63.2%
|
| Spain |
4
80%
|
3
42.9%
|
1
25%
|
1
20%
|
2
40%
|
4
44.4%
|
4
25%
|
2
33.3%
|
21
36.8%
|
| ECOG PS (Count of Participants) | |||||||||
| 0 |
1
20%
|
1
14.3%
|
0
0%
|
0
0%
|
3
60%
|
2
22.2%
|
5
31.3%
|
3
50%
|
15
26.3%
|
| 1 |
4
80%
|
6
85.7%
|
4
100%
|
5
100%
|
2
40%
|
7
77.8%
|
11
68.8%
|
3
50%
|
42
73.7%
|
| Body surface area (m^2) [Median (Full Range) ] | |||||||||
| Median (Full Range) [m^2] |
1.6
|
1.7
|
2.0
|
1.7
|
1.9
|
1.8
|
1.8
|
1.6
|
1.8
|
| Tumor type (Count of Participants) | |||||||||
| NSCLC |
3
60%
|
5
71.4%
|
1
25%
|
2
40%
|
1
20%
|
3
33.3%
|
3
18.8%
|
0
0%
|
18
31.6%
|
| Gynecological (endometrial or cervical) |
0
0%
|
2
28.6%
|
0
0%
|
1
20%
|
0
0%
|
3
33.3%
|
6
37.5%
|
1
16.7%
|
13
22.8%
|
| Epithelial ovarian cancer |
0
0%
|
0
0%
|
2
50%
|
1
20%
|
3
60%
|
1
11.1%
|
5
31.3%
|
1
16.7%
|
13
22.8%
|
| Breast cancer |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
1
6.3%
|
2
33.3%
|
4
7%
|
| GIST |
1
20%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
1
6.3%
|
0
0%
|
3
5.3%
|
| Head and neck cancer |
1
20%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
3
5.3%
|
| GCTs |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
1
16.7%
|
2
3.5%
|
| Adenocarcinoma or carcinoma of unknown primary site |
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Time from diagnosis to first infusion (months) [Median (Full Range) ] | |||||||||
| Median (Full Range) [months] |
30.2
|
43.0
|
23.2
|
34.3
|
23.4
|
33.9
|
44.5
|
48.8
|
48.8
|
| Time from last progressive disease to first infusion (months) [Median (Full Range) ] | |||||||||
| Median (Full Range) [months] |
1.6
|
1.0
|
2.2
|
1.7
|
1.4
|
2.4
|
1.2
|
0.7
|
1.4
|
| Time-to-progression of last prior therapy (months) [Median (Full Range) ] | |||||||||
| Median (Full Range) [months] |
1.6
|
3.8
|
3.4
|
6.7
|
11.7
|
5.4
|
3.0
|
2.9
|
3.7
|
| Bulky disease (Count of Participants) | |||||||||
| Count of Participants [Participants] |
1
20%
|
1
14.3%
|
1
25%
|
0
0%
|
1
20%
|
3
33.3%
|
5
31.3%
|
2
33.3%
|
14
24.6%
|
| Site involvement at baseline (sites) [Median (Full Range) ] | |||||||||
| Median (Full Range) [sites] |
3
|
4
|
4.5
|
3
|
3
|
4
|
4
|
3.5
|
4
|
| Lines of prior anticancer therapies (lines) [Median (Full Range) ] | |||||||||
| Median (Full Range) [lines] |
2
|
3
|
3
|
2
|
3
|
3
|
3
|
3.5
|
3
|
| Agents of prior anticancer therapies (Agents) [Median (Full Range) ] | |||||||||
| Median (Full Range) [Agents] |
4
|
4
|
4.5
|
5
|
3
|
3
|
4.5
|
5
|
4
|
Outcome Measures
| Title | Number of Participants With Dose Limiting Toxicities |
|---|---|
| Description | Dose-limiting toxicities were defined as: Grade 4 neutropenia lasting >3 days Grade≥3 febrile neutropenia of any duration or neutropenic sepsis Grade 4 thrombocytopenia or grade 3 with any major bleeding episode requiring a platelet transfusion Grade 4 ALT/AST increase, or grade 3 lasting >7 days Treatment-related grade≥2 ALT/AST increase concomitantly with ≥2 x ULN total bilirubin increase and normal AP Any other grade≥3 non-hematological AE that was suspected to be related to study drugs, except nausea/vomiting, hypersensitivity reactions, extravasations, grade 3 asthenia lasting less than one week, anorexia, and non-clinically relevant isolated biochemical abnormalities Delay in the administration of Cycle 2 of the combination exceeding seven (+1) days of the treatment due date due to any AEs related to study drugs. The following circumstances were to be discussed between the Principal Investigator and the Sponsor, and the final consensus had to be documented |
| Time Frame | From the start of treatment to the end of cycle one which are 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Thirteen patients were not evaluable: 11 patients because they did not complete Cycle 1, and two patients because they were withdrawn from the study before receiving the first study drug infusion. |
| Arm/Group Title | GEM/PM060184 Dose Level I | GEM/PM060184 Dose Level II | GEM/PM060184 Dose Level III | GEM/PM060184 Dose Level IV | GEM/PM060184 Dose Level V | GEM/PM060184 Dose Level VI | GEM/PM060184 Dose Level VII | GEM/PM060184 Dose Level VIII |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level I: 800 mg/m^2 GEM / 6.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level II: 800 mg/m^2 GEM / 7.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level III: 1000 mg/m^2 GEM / 6.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level IV: 1000 mg/m^2 GEM / 8.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level V: 1000 mg/m^2 GEM / 9.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VI: 1000 mg/m^2 GEM / 9.3 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VII:1000 mg/m^2 GEM / 10.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VIII:1000 mg/m^2 GEM / 10.5 mg/m^2 PM060184 |
| Measure Participants | 3 | 6 | 3 | 3 | 4 | 7 | 13 | 5 |
| Count of Participants [Participants] |
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
1
6.3%
|
1
16.7%
|
| Title | Number of Participants With Clinical Benefit |
|---|---|
| Description | Clinical benefit defined as any response or stable disease ≥4 months. 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 (this includes the baseline sum if that is the smallest 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. |
| Time Frame | Every two cycles (every six weeks ± one week) until Cycle 4, and then every three cycles (every nine weeks ± one week) while on treatment, up to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Eleven patients were not evaluable: nine patients because they were withdrawn from the study before undergoing a tumor assessment, and two patients because they were withdrawn from the study before receiving the first study drug infusion |
| Arm/Group Title | GEM/PM060184 Dose Level I | GEM/PM060184 Dose Level II | GEM/PM060184 Dose Level III | GEM/PM060184 Dose Level IV | GEM/PM060184 Dose Level V | GEM/PM060184 Dose Level VI | GEM/PM060184 Dose Level VII | GEM/PM060184 Dose Level VIII |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level I: 800 mg/m^2 GEM / 6.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level II: 800 mg/m^2 GEM / 7.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level III: 1000 mg/m^2 GEM / 6.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level IV: 1000 mg/m^2 GEM / 8.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level V: 1000 mg/m^2 GEM / 9.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VI: 1000 mg/m^2 GEM / 9.3 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VII:1000 mg/m^2 GEM / 10.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VIII:1000 mg/m^2 GEM / 10.5 mg/m^2 PM060184 |
| Measure Participants | 4 | 6 | 3 | 4 | 4 | 9 | 11 | 5 |
| Count of Participants [Participants] |
1
20%
|
3
42.9%
|
2
50%
|
1
20%
|
1
20%
|
2
22.2%
|
6
37.5%
|
2
33.3%
|
Adverse Events
| Time Frame | Participants were assessed through study completion, approximately 2 years | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Two patients were never treated with plitidepsin and were excluded from the analysis of safety. | |||||||||||||||
| Arm/Group Title | GEM/PM060184 Dose Level I | GEM/PM060184 Dose Level II | GEM/PM060184 Dose Level III | GEM/PM060184 Dose Level IV | GEM/PM060184 Dose Level V | GEM/PM060184 Dose Level VI | GEM/PM060184 Dose Level VII | GEM/PM060184 Dose Level VIII | ||||||||
| Arm/Group Description | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level I: 800 mg/m^2 GEM / 6.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level II: 800 mg/m^2 GEM / 7.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level III: 1000 mg/m^2 GEM / 6.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level IV: 1000 mg/m^2 GEM / 8.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level V: 1000 mg/m^2 GEM / 9.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VI: 1000 mg/m^2 GEM / 9.3 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VII:1000 mg/m^2 GEM / 10.0 mg/m^2 PM060184 | Patients were to receive GEM first, followed by PM060184, both on Day 1 and Day 8 q3wk. Administration of study treatment was as follows: GEM: i.v. infusion over 30 min (± 10 min) via a central or peripheral venous catheter through a pump device, followed by: PM060184: i.v. infusion over 10 min (± 3 min) via a central or peripheral venous catheter through a pump device. Dose Level VIII:1000 mg/m^2 GEM / 10.5 mg/m^2 PM060184 | ||||||||
All Cause Mortality |
||||||||||||||||
| GEM/PM060184 Dose Level I | GEM/PM060184 Dose Level II | GEM/PM060184 Dose Level III | GEM/PM060184 Dose Level IV | GEM/PM060184 Dose Level V | GEM/PM060184 Dose Level VI | GEM/PM060184 Dose Level VII | GEM/PM060184 Dose Level VIII | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/4 (25%) | 1/7 (14.3%) | 0/4 (0%) | 0/5 (0%) | 1/5 (20%) | 0/9 (0%) | 5/16 (31.3%) | 0/5 (0%) | ||||||||
Serious Adverse Events |
||||||||||||||||
| GEM/PM060184 Dose Level I | GEM/PM060184 Dose Level II | GEM/PM060184 Dose Level III | GEM/PM060184 Dose Level IV | GEM/PM060184 Dose Level V | GEM/PM060184 Dose Level VI | GEM/PM060184 Dose Level VII | GEM/PM060184 Dose Level VIII | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 3/7 (42.9%) | 2/4 (50%) | 1/5 (20%) | 3/5 (60%) | 3/9 (33.3%) | 8/16 (50%) | 4/5 (80%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Anaemia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Thrombocytopenia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||
| Tachycardia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal pain | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 1/4 (25%) | 2 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 2/16 (12.5%) | 2 | 0/5 (0%) | 0 |
| Constipation | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Vomiting | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 2/16 (12.5%) | 4 | 0/5 (0%) | 0 |
| Small intestinal obstruction | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 2/5 (40%) | 2 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Haematochezia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Nausea | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 3/16 (18.8%) | 5 | 0/5 (0%) | 0 |
| Intestinal obstruction | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| General disorders | ||||||||||||||||
| Pyrexia | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Chest pain | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Chills | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Oedema peripheral | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Infections and infestations | ||||||||||||||||
| Infection | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Urinary tract infection | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Sepsis | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 2 | 0/5 (0%) | 0 |
| Appendicitis | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Pneumonia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Investigations | ||||||||||||||||
| Alanine aminotransferase increased | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Hyperkalaemia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||
| Female genital tract fistula | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Respiratory failure | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Pulmonary embolism | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Dyspnoea | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 1/5 (20%) | 2 | 0/9 (0%) | 0 | 1/16 (6.3%) | 2 | 0/5 (0%) | 0 |
| Pleural effusion | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Respiratory arrest | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Pneumonitis | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| GEM/PM060184 Dose Level I | GEM/PM060184 Dose Level II | GEM/PM060184 Dose Level III | GEM/PM060184 Dose Level IV | GEM/PM060184 Dose Level V | GEM/PM060184 Dose Level VI | GEM/PM060184 Dose Level VII | GEM/PM060184 Dose Level VIII | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 7/7 (100%) | 4/4 (100%) | 5/5 (100%) | 5/5 (100%) | 9/9 (100%) | 16/16 (100%) | 5/5 (100%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Anaemia | 2/4 (50%) | 2 | 2/7 (28.6%) | 4 | 2/4 (50%) | 3 | 1/5 (20%) | 1 | 1/5 (20%) | 1 | 3/9 (33.3%) | 14 | 7/16 (43.8%) | 28 | 3/5 (60%) | 6 |
| Neutropenia | 3/4 (75%) | 3 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 3/16 (18.8%) | 4 | 2/5 (40%) | 7 |
| Normochromic normocytic anaemia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Thrombocytopenia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 3 | 2/16 (12.5%) | 6 | 0/5 (0%) | 0 |
| Lymph node pain | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||
| Palpitations | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 2 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Atrial fibrillation | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Bradycardia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 2 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Tachycardia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||
| Ear discomfort | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Ear pain | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Eye disorders | ||||||||||||||||
| Cataract | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Dry eye | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Vitreous detachment | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Eye pain | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal pain | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 2 | 1/9 (11.1%) | 1 | 6/16 (37.5%) | 9 | 2/5 (40%) | 6 |
| Ascites | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Constipation | 1/4 (25%) | 1 | 1/7 (14.3%) | 2 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 2/5 (40%) | 2 | 4/9 (44.4%) | 5 | 8/16 (50%) | 13 | 4/5 (80%) | 9 |
| Diarrhoea | 1/4 (25%) | 1 | 2/7 (28.6%) | 4 | 1/4 (25%) | 2 | 2/5 (40%) | 2 | 1/5 (20%) | 1 | 2/9 (22.2%) | 5 | 8/16 (50%) | 20 | 2/5 (40%) | 4 |
| Dyspepsia | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 3/16 (18.8%) | 4 | 0/5 (0%) | 0 |
| Nausea | 2/4 (50%) | 7 | 5/7 (71.4%) | 7 | 0/4 (0%) | 0 | 2/5 (40%) | 2 | 4/5 (80%) | 8 | 4/9 (44.4%) | 5 | 11/16 (68.8%) | 17 | 4/5 (80%) | 8 |
| Vomiting | 1/4 (25%) | 1 | 3/7 (42.9%) | 4 | 1/4 (25%) | 2 | 1/5 (20%) | 1 | 2/5 (40%) | 2 | 2/9 (22.2%) | 4 | 6/16 (37.5%) | 9 | 3/5 (60%) | 4 |
| Dysphagia | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Proctalgia | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Rectal haemorrhage | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 2 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Stomatitis | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Abdominal discomfort | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 2/5 (40%) | 2 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Abdominal pain upper | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 1/5 (20%) | 1 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 1/5 (20%) | 1 |
| Haematemesis | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Odynophagia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Abdominal pain lower | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 2 | 3/16 (18.8%) | 5 | 1/5 (20%) | 1 |
| Enterovesical fistula | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 3 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Haematochezia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Tooth loss | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Dry mouth | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 2/16 (12.5%) | 2 | 1/5 (20%) | 1 |
| Gastrooesophageal reflux disease | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| General disorders | ||||||||||||||||
| Asthenia | 1/4 (25%) | 1 | 1/7 (14.3%) | 1 | 1/4 (25%) | 5 | 1/5 (20%) | 2 | 2/5 (40%) | 7 | 4/9 (44.4%) | 9 | 3/16 (18.8%) | 5 | 1/5 (20%) | 2 |
| Fatigue | 1/4 (25%) | 1 | 5/7 (71.4%) | 11 | 3/4 (75%) | 8 | 3/5 (60%) | 6 | 3/5 (60%) | 12 | 2/9 (22.2%) | 4 | 10/16 (62.5%) | 27 | 3/5 (60%) | 8 |
| Pyrexia | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 2/5 (40%) | 4 | 0/5 (0%) | 0 | 2/9 (22.2%) | 3 | 2/16 (12.5%) | 4 | 1/5 (20%) | 1 |
| Mucosal inflammation | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Oedema peripheral | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 4 | 1/5 (20%) | 1 |
| Catheter site erythema | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Local swelling | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Chest discomfort | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Gait disturbance | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Pain | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 2/16 (12.5%) | 2 | 1/5 (20%) | 1 |
| Chills | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 1/5 (20%) | 2 |
| Feeling of body temperature change | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Infusion site discolouration | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Malaise | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Oedema | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Catheter site pain | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Hepatobiliary disorders | ||||||||||||||||
| Hyperbilirubinaemia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Infections and infestations | ||||||||||||||||
| Upper respiratory tract infection | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Urinary tract infection | 1/4 (25%) | 2 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 2 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Pneumonia | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Herpes zoster | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Wound infection | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Respiratory tract infection | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 1/9 (11.1%) | 2 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Conjunctivitis viral | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Cystitis | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Device related infection | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Fungal skin infection | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||
| Wound | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 3 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Fall | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 1/9 (11.1%) | 1 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Infusion related reaction | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Contusion | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Investigations | ||||||||||||||||
| Weight decreased | 1/4 (25%) | 1 | 2/7 (28.6%) | 2 | 0/4 (0%) | 0 | 2/5 (40%) | 4 | 1/5 (20%) | 1 | 1/9 (11.1%) | 1 | 8/16 (50%) | 10 | 2/5 (40%) | 3 |
| Breath sounds abnormal | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Creatinine renal clearance decreased | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Alanine aminotransferase increased | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Blood urine present | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Weight increased | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Aspartate aminotransferase increased | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Blood bilirubin increased | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Blood creatinine increased | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Decreased appetite | 1/4 (25%) | 1 | 1/7 (14.3%) | 1 | 1/4 (25%) | 1 | 2/5 (40%) | 2 | 2/5 (40%) | 2 | 2/9 (22.2%) | 2 | 11/16 (68.8%) | 21 | 3/5 (60%) | 3 |
| Hyponatraemia | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Dehydration | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Hypomagnesaemia | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Hypocalcaemia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Hyperglycaemia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Hyperkalaemia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 1/5 (20%) | 1 |
| Hypokalaemia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 1/5 (20%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Arthralgia | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 1/16 (6.3%) | 1 | 2/5 (40%) | 13 |
| Back pain | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 2 | 1/5 (20%) | 3 | 1/9 (11.1%) | 1 | 2/16 (12.5%) | 2 | 1/5 (20%) | 1 |
| Groin pain | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 2 | 0/5 (0%) | 0 |
| Musculoskeletal pain | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 3 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 3/16 (18.8%) | 4 | 2/5 (40%) | 2 |
| Myalgia | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 3/16 (18.8%) | 3 | 0/5 (0%) | 0 |
| Musculoskeletal chest pain | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Pain in extremity | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 1/4 (25%) | 2 | 1/5 (20%) | 2 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 4 | 2/5 (40%) | 3 |
| Bone pain | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 2/5 (40%) | 2 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Muscular weakness | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 2/5 (40%) | 4 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Pain in jaw | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Muscle spasms | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 2/16 (12.5%) | 2 | 1/5 (20%) | 1 |
| Musculoskeletal stiffness | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Tumour pain | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 1/5 (20%) | 1 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||
| Dizziness | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 1/5 (20%) | 3 | 2/9 (22.2%) | 3 | 2/16 (12.5%) | 2 | 1/5 (20%) | 1 |
| Paraesthesia | 1/4 (25%) | 1 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 2/16 (12.5%) | 3 | 0/5 (0%) | 0 |
| Peripheral sensory neuropathy | 1/4 (25%) | 1 | 1/7 (14.3%) | 2 | 1/4 (25%) | 12 | 0/5 (0%) | 0 | 1/5 (20%) | 3 | 1/9 (11.1%) | 3 | 2/16 (12.5%) | 3 | 0/5 (0%) | 0 |
| Neurotoxicity | 0/4 (0%) | 0 | 1/7 (14.3%) | 2 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 1/5 (20%) | 1 | 1/9 (11.1%) | 1 | 1/16 (6.3%) | 3 | 0/5 (0%) | 0 |
| Tremor | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Neuralgia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Neuropathy peripheral | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 1/9 (11.1%) | 2 | 6/16 (37.5%) | 9 | 2/5 (40%) | 4 |
| Dysarthria | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Presyncope | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Headache | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 4/16 (25%) | 5 | 1/5 (20%) | 1 |
| Hypoaesthesia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Syncope | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||
| Insomnia | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Anxiety | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 3/16 (18.8%) | 3 | 0/5 (0%) | 0 |
| Depression | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||
| Haematuria | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Pollakiuria | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Dysuria | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 2/16 (12.5%) | 2 | 0/5 (0%) | 0 |
| Urinary incontinence | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Urethritis noninfective | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 2/9 (22.2%) | 2 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Hydronephrosis | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 2/16 (12.5%) | 2 | 0/5 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||
| Female genital tract fistula | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Pelvic pain | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 1/5 (20%) | 1 |
| Vulvovaginal pain | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Epistaxis | 1/4 (25%) | 1 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 2/16 (12.5%) | 2 | 0/5 (0%) | 0 |
| Cough | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 2/16 (12.5%) | 3 | 1/5 (20%) | 3 |
| Dyspnoea | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 3/5 (60%) | 4 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 3/16 (18.8%) | 3 | 1/5 (20%) | 1 |
| Haemoptysis | 0/4 (0%) | 0 | 1/7 (14.3%) | 2 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Oropharyngeal pain | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 1/4 (25%) | 2 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Sneezing | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Dysphonia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Productive cough | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 1/5 (20%) | 1 | 1/5 (20%) | 1 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Hiccups | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Respiratory failure | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Rhinitis allergic | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Dyspnoea exertional | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 3/16 (18.8%) | 3 | 0/5 (0%) | 0 |
| Hypoxia | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Wheezing | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 2/16 (12.5%) | 2 | 1/5 (20%) | 1 |
| Nasal congestion | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Rhinorrhoea | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Alopecia | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Nail disorder | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Night sweats | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Skin hyperpigmentation | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Rash maculo-papular | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 4 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Pruritus | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/5 (20%) | 1 | 1/9 (11.1%) | 1 | 2/16 (12.5%) | 2 | 0/5 (0%) | 0 |
| Hyperhidrosis | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 2 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Rash | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Pruritus generalised | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 2/16 (12.5%) | 2 | 0/5 (0%) | 0 |
| Rash macular | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Skin disorder | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
| Dry skin | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Nail discolouration | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 1/5 (20%) | 1 |
| Vascular disorders | ||||||||||||||||
| Hypertension | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 2 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Orthostatic hypotension | 0/4 (0%) | 0 | 1/7 (14.3%) | 1 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Subclavian vein thrombosis | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Thrombophlebitis | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Vulvovaginal pruritus | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 1/9 (11.1%) | 1 | 0/16 (0%) | 0 | 0/5 (0%) | 0 |
| Hypotension | 0/4 (0%) | 0 | 0/7 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/5 (0%) | 0 | 0/9 (0%) | 0 | 1/16 (6.3%) | 1 | 0/5 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Clinical Developtment, Department of PharmaMar´s Oncology., Business Unit. |
|---|---|
| Organization | Pharma Mar, S.A. |
| Phone | +34 918466000 |
| clinicaltrials@pharmamar.com |
Responsible Party:
PharmaMar
ClinicalTrials.gov Identifier:
NCT02533674
Other Study ID Numbers:
- PM60184-A-003-14
- PM60184-A-003-14
- 2014-002943-16
First Posted:
Aug 27, 2015
Last Update Posted:
Jun 11, 2021
Last Verified:
May 1, 2021