Breast Cancer, Gynecological Cancer, Head and Neck Carcinoma, Non-small Cell Lung Cancer, Non-squamous Cell Lung Cancer, Ovarian Cancer, Small Cell Lung Cancer
Conditions
Brief summary
Clinical trial of PM01183 in combination with paclitaxel, with or without bevacizumab, in patients with solid tumors
Detailed description
Clinical trial to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with weekly paclitaxel, with or without bevacizumab. Once a recommended dose is defined for the PM01183 and weekly paclitaxel combination, the feasibility of adding bevacizumab to this combination will be explored in a selected cohort of patients to characterize the safety profile and feasibility of this combination, to obtain preliminary information on antitumor activity, to obtain preliminary information on quality of life (QoL), to characterize the pharmacokinetics (PK) of this combination and to detect major drug-drug PK interactions and PK(pharmacokinetic)/PD(pharmacodynamic) correlation and to conduct an exploratory pharmacogenomic(PGx) analysis in patients with selected advanced solid tumors.
Interventions
DRUGPM01183 + paclitaxel +/- bevacizumab
PM01183: 1 mg and 4 mg vials. Powder for concentrate for solution for infusion paclitaxel: 6 mg/ml concentrate for solution for infusion bevacizumab: 25 mg/ml concentrate for solution for infusion Once a recommended dose is defined for the PM01183 and weekly paclitaxel combination, the feasibility of adding bevacizumab to this combination will be explored in a prospectively selected cohort of patients
Sponsors
PharmaMar
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Voluntarily signed and dated written informed consent * Age between 18 and 75 years old (both inclusive) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1 * Life expectancy ≥ 3 months. * Patients with a histologically/cytologically confirmed diagnosis of advanced and/or unresectable disease of any of the following tumors: 1. Breast cancer 2. Epithelial ovarian cancer or gynecological cancer 3. Head and neck squamous cell carcinoma 4. Non-small cell lung cancer 5. Small cell lung cancer 6. Platinum-refractory germ-cell tumors. 7. Adenocarcinoma or carcinoma of unknown primary site * Adequate bone marrow, renal, hepatic, and metabolic function * Recovery to grade ≤ 1 or to baseline from any Adverse Event (AE) derived from previous treatment (excluding alopecia of any grade). * Pre-menopausal women must have a negative pregnancy test before study entry and agree to use a medically acceptable method of contraception throughout the treatment period and for at least six weeks after treatment discontinuation
Exclusion criteria
* Prior treatment with PM01183 or weekly paclitaxel or nanoalbumin-paclitaxel * Patients who have previously discontinued paclitaxel-based regimes due to drug related toxicity. * Known hypersensitivity to bevacizumab or any component of its formulation * Patients who have previously discontinued bevacizumab-containing regimes due to drug-related toxicity. * More than three prior lines of chemotherapy * Less than three months since last taxane-containing therapy. * Wash-out period: 1. Less than three weeks since the last chemotherapy-containing regimen 2. Less than three weeks since the last radiotherapy dose 3. Less than four weeks since last monoclonal antibody-containing therapy * Concomitant diseases/conditions: Unstable angina, myocardial infarction, valvular heart disease, encephalopathy, ischemic attacks, hemorrhagic or ischemic cerebrovascular accident (CVA) or ongoing pulmonary embolism within last year, arrhythmia, hepatopathy, uncontrolled infection, hemoptysis or oxygen requiring dyspnea, known HIV infection, bleeding risk, muscular problems, peripheral neuropathy, Symptomatic or progressive brain metastases or leptomeningeal disease. * Men or pre-menopausal women who are not using an effective method of contraception as previously described; actively breast feeding women. * Patients who have pelvic irradiation with doses ≥ 45 Grays (Gy). * History of previous bone marrow and/or stem cell transplantation. * Confirmed bone marrow involvement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | The MTD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks) | The MTD will be the lowest level at which one third or more evaluable patients experience a DLT in Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1. |
| Recommended Dose (RD) | The RD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks) | The RD will be the highest DL explored with less than one third of the patients experiencing a DLT during Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1. |
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | DLT was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks) | DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Tumor Response | Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks) | Best overall response:Best response recorded from the start of the study treatment until the end of treatment Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm Partial Response (PR):At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression) Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum diameters while on study Treatment failure (TF):symptomatic deterioration or death due to progression |
| Quality of Life (QoL) | Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks) | Change from baseline to last cycle. European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL scale scores. The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC QLQ-C30 (version 3.0) developed for palliative care. Wilcoxon signed ranks test repeat-measure analyses of variance were used to measure the change value from baseline value. Data has to be analysed following the corresponding EORTC manual http://www.eortc.be/qol/files/SCManualQLQ-C15-PAL.pdf and the overall quality of life assessment is contained in 0 to 100 where a higher value represents a better state. |
| Progression-free Survival | Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks) | Progression-free survival (PFS) was defined as the time from the date of first infusion of study treatment to the date of progression or death (due to any cause). If progression or death had not occurred at the time of the analysis, the PFS was censored. |
| Duration of Response (DR) | Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks) | Duration of response (DR) was defined as the time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented |
Countries
Spain, Switzerland, United States
Participant flow
Recruitment details
A total of 69 patients were enrolled at 3 investigational sites: 55 Group A (paclitaxel plus PM01183) and 14 Group B (paclitaxel+PM01183 and BEV). Patients participated in this trial between 15/Oct/2013 and 14/Jul/2016 (last FU). The first dose of the first cycle was given on 23/Oct/2013 and the last dose of the last cycle was given on 23/Jun/2016
Pre-assignment details
Signed IC,Age 18-75,ECOG PS≤1,Life expectancy≥3 months,Histologically/cytologically confirmed diagnosis of advanced and/or unresectable disease according to the groups,adequate status patient,no AEs,negative pregnancy test.
Participants by arm
| Arm | Count |
|---|---|
| Paclitaxel [60.0 mg/m2] / PM01183 [3.0 mg FD] Cohort I
* Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter.
* PM01183 3.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device.
Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement. | 3 |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] Cohort II
* Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter.
* PM01183 4.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device.
Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement. | 3 |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD Cohort III
* Paclitaxel 60.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter.
* PM01183 5.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device.
Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement. | 6 |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] Cohort IV
* Paclitaxel 80.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter.
* PM01183 5.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device.
Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement. | 6 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] Cohort V
* Paclitaxel 80.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour via a central or peripheral venous catheter through a pump device with an appropriate infusion line and filter.
* PM01183 4.0 mg FD as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour via a central catheter (or over a minimum dilution of 250 mL if a peripheral venous catheter was used) through a pump device.
Patients in this group were to receive paclitaxel and PM01183 for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, PM01183 could be continued alone until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement. | 37 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg All three study medications were administered via a central or a peripheral venous catheter through a pump device, as follows:
* Paclitaxel 80.0 mg/m2 as an i.v. infusion on Days 1, 8 and 15 q3wk, over one hour.
* PM01183 as an i.v. infusion on Day 1 q3wk, after paclitaxel infusion, over one hour.
* Bevacizumab (BEV) 15 mg/kg as an i.v. infusion on Day 1 q3wk, immediately after paclitaxel and PM01183 infusions, Minimum duration of infusion was 90 minutes for the first dose and, if well tolerated, 60 minutes for the second dose and 30 minutes for all subsequent doses. nous catheter was used) through a pump device.
Patients in this group were to receive paclitaxel, PM01183 and BEV for up to six cycles, in the absence of disease progression or unacceptable toxicity; then, both PM01183 and BEV could be continued until progression, unacceptable toxicity, patient's decision, or Investigator's decision upon the Sponsors' agreement. | 14 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Cohort B: Arm B | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Cohort B: Arm B | Global end of study | 0 | 0 | 0 | 0 | 0 | 1 |
| Cohort B: Arm B | Never treated | 0 | 0 | 0 | 0 | 0 | 2 |
| Cohort B: Arm B | Physician Decision | 0 | 0 | 0 | 0 | 0 | 2 |
| Cohort B: Arm B | Progressive disease | 0 | 0 | 0 | 0 | 0 | 8 |
| Cohort I: Dose Level 1 | Progressive disease | 3 | 0 | 0 | 0 | 0 | 0 |
| Cohort II: Dose Level 2 | Clinical progressive disease | 0 | 1 | 0 | 0 | 0 | 0 |
| Cohort II: Dose Level 2 | Progressive disease | 0 | 2 | 0 | 0 | 0 | 0 |
| Cohort III: Dose Level 3 | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 |
| Cohort III: Dose Level 3 | Global end of study | 0 | 0 | 1 | 0 | 0 | 0 |
| Cohort III: Dose Level 3 | Progressive disease | 0 | 0 | 3 | 0 | 0 | 0 |
| Cohort III: Dose Level 3 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
| Cohort IV: Dose Level 4 | Progressive disease | 0 | 0 | 0 | 6 | 0 | 0 |
| Cohort V: Dose Level 5 | Death | 0 | 0 | 0 | 0 | 1 | 0 |
| Cohort V: Dose Level 5 | Global end of study | 0 | 0 | 0 | 0 | 2 | 0 |
| Cohort V: Dose Level 5 | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Cohort V: Dose Level 5 | Progressive disease | 0 | 0 | 0 | 0 | 30 | 0 |
| Cohort V: Dose Level 5 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Paclitaxel [60.0 mg/m2] / PM01183 [3.0 mg FD] | Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 14 Participants | 2 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 6 Participants | 5 Participants | 23 Participants | 12 Participants | 51 Participants |
| Age, Continuous | 57 years | 50 years | 53.5 years | 46.5 years | 61.0 years | 57 years | 57 years |
| Region of Enrollment Spain | 2 Participants | 1 Participants | 3 Participants | 4 Participants | 12 Participants | 6 Participants | 28 Participants |
| Region of Enrollment Switzerland | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 6 Participants | 1 Participants | 12 Participants |
| Region of Enrollment United States | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 19 Participants | 7 Participants | 29 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 4 Participants | 5 Participants | 26 Participants | 8 Participants | 48 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 11 Participants | 6 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 3 / 37 | 2 / 14 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 | 6 / 6 | 36 / 37 | 12 / 14 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 3 / 6 | 2 / 6 | 15 / 37 | 7 / 14 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
The MTD will be the lowest level at which one third or more evaluable patients experience a DLT in Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.
Time frame: The MTD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)
Population: Three patients at the RD were not evaluable because they did not receive a complete Cycle 1 due to disease-related grade 3 vomiting and early PD, disease-related grade 3 confusional state, and because not enough information for DLT evaluation was collected during Cycle 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A (Paclitaxel/PM01183) | Maximum Tolerated Dose (MTD) | NA mg/m2 / mg FD |
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.
Time frame: DLT was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A (Paclitaxel/PM01183) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 2 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 3 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 6 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 3 Participants |
Primary
Recommended Dose (RD)
The RD will be the highest DL explored with less than one third of the patients experiencing a DLT during Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.
Time frame: The RD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)
Population: Three patients at the RD were not evaluable because they did not receive a complete Cycle 1 due to disease-related grade 3 vomiting and early PD, disease-related grade 3 confusional state, and because not enough information for DLT evaluation was collected during Cycle 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A (Paclitaxel/PM01183) | Recommended Dose (RD) | NA mg/m2 / mg FD |
Secondary
Best Tumor Response
Best overall response:Best response recorded from the start of the study treatment until the end of treatment Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm Partial Response (PR):At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression) Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum diameters while on study Treatment failure (TF):symptomatic deterioration or death due to progression
Time frame: Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A (Paclitaxel/PM01183) | Best Tumor Response | SD ≥3 months | 1 Participants |
| Group A (Paclitaxel/PM01183) | Best Tumor Response | PR | 1 Participants |
| Group A (Paclitaxel/PM01183) | Best Tumor Response | TF | 0 Participants |
| Group A (Paclitaxel/PM01183) | Best Tumor Response | CR | 0 Participants |
| Group A (Paclitaxel/PM01183) | Best Tumor Response | Early PD | 0 Participants |
| Group A (Paclitaxel/PM01183) | Best Tumor Response | PD | 1 Participants |
| Group A (Paclitaxel/PM01183) | Best Tumor Response | SD <3 months | 0 Participants |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | SD <3 months | 0 Participants |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | CR | 0 Participants |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | PR | 0 Participants |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | SD ≥3 months | 2 Participants |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | PD | 1 Participants |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | Early PD | 0 Participants |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | TF | 0 Participants |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Best Tumor Response | TF | 0 Participants |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Best Tumor Response | SD <3 months | 1 Participants |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Best Tumor Response | Early PD | 0 Participants |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Best Tumor Response | SD ≥3 months | 1 Participants |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Best Tumor Response | PR | 2 Participants |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Best Tumor Response | CR | 0 Participants |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Best Tumor Response | PD | 2 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Best Tumor Response | TF | 0 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Best Tumor Response | SD ≥3 months | 1 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Best Tumor Response | Early PD | 0 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Best Tumor Response | PR | 4 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Best Tumor Response | CR | 0 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Best Tumor Response | SD <3 months | 0 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Best Tumor Response | PD | 1 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | PR | 12 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | CR | 1 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | SD ≥3 months | 6 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | SD <3 months | 1 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | PD | 12 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | TF | 0 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Best Tumor Response | Early PD | 1 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Best Tumor Response | PR | 4 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Best Tumor Response | Early PD | 0 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Best Tumor Response | CR | 1 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Best Tumor Response | TF | 1 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Best Tumor Response | SD <3 months | 0 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Best Tumor Response | SD ≥3 months | 4 Participants |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Best Tumor Response | PD | 0 Participants |
Secondary
Duration of Response (DR)
Duration of response (DR) was defined as the time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented
Time frame: Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)
Population: In cohort II, no patients with PR or CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (Paclitaxel/PM01183) | Duration of Response (DR) | 1.6 months |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Duration of Response (DR) | NA months |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Duration of Response (DR) | 2.2 months |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Duration of Response (DR) | 4.1 months |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Duration of Response (DR) | 4.6 months |
Secondary
Progression-free Survival
Progression-free survival (PFS) was defined as the time from the date of first infusion of study treatment to the date of progression or death (due to any cause). If progression or death had not occurred at the time of the analysis, the PFS was censored.
Time frame: Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (Paclitaxel/PM01183) | Progression-free Survival | 3.5 months |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Progression-free Survival | 3.1 months |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Progression-free Survival | 3.1 months |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Progression-free Survival | 5.4 months |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Progression-free Survival | 3.9 months |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Progression-free Survival | 6.7 months |
Secondary
Quality of Life (QoL)
Change from baseline to last cycle. European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL scale scores. The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC QLQ-C30 (version 3.0) developed for palliative care. Wilcoxon signed ranks test repeat-measure analyses of variance were used to measure the change value from baseline value. Data has to be analysed following the corresponding EORTC manual http://www.eortc.be/qol/files/SCManualQLQ-C15-PAL.pdf and the overall quality of life assessment is contained in 0 to 100 where a higher value represents a better state.
Time frame: Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A (Paclitaxel/PM01183) | Quality of Life (QoL) | Appetite loss | -22.2 score on a scale | Standard Deviation 38.5 |
| Group A (Paclitaxel/PM01183) | Quality of Life (QoL) | Insomnia | 0.0 score on a scale | Standard Deviation 33.3 |
| Group A (Paclitaxel/PM01183) | Quality of Life (QoL) | Emotional functioning | 16.7 score on a scale | Standard Deviation 28.9 |
| Group A (Paclitaxel/PM01183) | Quality of Life (QoL) | Nausea / vomiting | -5.6 score on a scale | Standard Deviation 9.6 |
| Group A (Paclitaxel/PM01183) | Quality of Life (QoL) | Fatigue | 3.7 score on a scale | Standard Deviation 33.9 |
| Group A (Paclitaxel/PM01183) | Quality of Life (QoL) | Physical functioning | -11.1 score on a scale | Standard Deviation 19.2 |
| Group A (Paclitaxel/PM01183) | Quality of Life (QoL) | Dyspnea | 0.0 score on a scale | Standard Deviation 0 |
| Group A (Paclitaxel/PM01183) | Quality of Life (QoL) | Pain | 5.6 score on a scale | Standard Deviation 9.6 |
| Group A (Paclitaxel/PM01183) | Quality of Life (QoL) | Overall QoL | 5.6 score on a scale | Standard Deviation 9.6 |
| Group A (Paclitaxel/PM01183) | Quality of Life (QoL) | Constipation | 11.1 score on a scale | Standard Deviation 19.2 |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Dyspnea | 0.0 score on a scale | Standard Deviation 47.1 |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Pain | 8.3 score on a scale | Standard Deviation 11.8 |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Insomnia | 16.7 score on a scale | Standard Deviation 23.6 |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Appetite loss | 0.0 score on a scale | Standard Deviation 0 |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Constipation | 0.0 score on a scale | Standard Deviation 0 |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Overall QoL | -16.7 score on a scale | Standard Deviation 0 |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Physical functioning | -6.7 score on a scale | Standard Deviation 9.4 |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Fatigue | 0.0 score on a scale | Standard Deviation 0 |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Nausea / vomiting | 8.3 score on a scale | Standard Deviation 11.8 |
| Paclitaxel [60.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Emotional functioning | -8.3 score on a scale | Standard Deviation 35.4 |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Quality of Life (QoL) | Appetite loss | -6.7 score on a scale | Standard Deviation 14.9 |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Quality of Life (QoL) | Fatigue | -2.2 score on a scale | Standard Deviation 24.1 |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Quality of Life (QoL) | Pain | -13.3 score on a scale | Standard Deviation 21.7 |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Quality of Life (QoL) | Constipation | 6.7 score on a scale | Standard Deviation 14.9 |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Quality of Life (QoL) | Insomnia | 0.0 score on a scale | Standard Deviation 0 |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Quality of Life (QoL) | Dyspnea | -6.7 score on a scale | Standard Deviation 27.9 |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Quality of Life (QoL) | Overall QoL | -8.3 score on a scale | Standard Deviation 21.5 |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Quality of Life (QoL) | Nausea / vomiting | 0.0 score on a scale | Standard Deviation 11.8 |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Quality of Life (QoL) | Emotional functioning | 0.0 score on a scale | Standard Deviation 11.8 |
| Paclitaxel 60.0 mg/m2 / PM01183 5.0 mg FD | Quality of Life (QoL) | Physical functioning | -2.7 score on a scale | Standard Deviation 6 |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Quality of Life (QoL) | Physical functioning | -13.3 score on a scale | Standard Deviation 8.2 |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Quality of Life (QoL) | Fatigue | 11.1 score on a scale | Standard Deviation 13.6 |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Quality of Life (QoL) | Dyspnea | 6.7 score on a scale | Standard Deviation 14.9 |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Quality of Life (QoL) | Emotional functioning | 5.0 score on a scale | Standard Deviation 33.1 |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Quality of Life (QoL) | Nausea / vomiting | 3.3 score on a scale | Standard Deviation 7.5 |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Quality of Life (QoL) | Pain | 13.3 score on a scale | Standard Deviation 13.9 |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Quality of Life (QoL) | Overall QoL | -6.7 score on a scale | Standard Deviation 19 |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Quality of Life (QoL) | Constipation | 13.3 score on a scale | Standard Deviation 29.8 |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Quality of Life (QoL) | Appetite loss | 0.0 score on a scale | Standard Deviation 0 |
| Paclitaxel [80.0 mg/m2] / PM01183 [5.0 mg FD] | Quality of Life (QoL) | Insomnia | -6.7 score on a scale | Standard Deviation 14.9 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Physical functioning | -2.8 score on a scale | Standard Deviation 19.8 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Appetite loss | 1.4 score on a scale | Standard Deviation 30.3 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Constipation | -2.8 score on a scale | Standard Deviation 23.9 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Overall QoL | -6.3 score on a scale | Standard Deviation 22.4 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Pain | -4.2 score on a scale | Standard Deviation 21 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Fatigue | 6.5 score on a scale | Standard Deviation 23.4 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Emotional functioning | 6.3 score on a scale | Standard Deviation 18.4 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Nausea / vomiting | 3.5 score on a scale | Standard Deviation 9.8 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Insomnia | 4.2 score on a scale | Standard Deviation 34.5 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] | Quality of Life (QoL) | Dyspnea | 11.1 score on a scale | Standard Deviation 25.4 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Quality of Life (QoL) | Overall QoL | -10.4 score on a scale | Standard Deviation 17.7 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Quality of Life (QoL) | Emotional functioning | 5.2 score on a scale | Standard Deviation 16 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Quality of Life (QoL) | Dyspnea | 12.5 score on a scale | Standard Deviation 24.8 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Quality of Life (QoL) | Insomnia | -12.5 score on a scale | Standard Deviation 30.5 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Quality of Life (QoL) | Constipation | 8.3 score on a scale | Standard Deviation 23.6 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Quality of Life (QoL) | Physical functioning | -8.3 score on a scale | Standard Deviation 17 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Quality of Life (QoL) | Appetite loss | 16.7 score on a scale | Standard Deviation 25.2 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Quality of Life (QoL) | Fatigue | 2.8 score on a scale | Standard Deviation 22 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Quality of Life (QoL) | Pain | 12.5 score on a scale | Standard Deviation 30.5 |
| Paclitaxel [80.0 mg/m2] / PM01183 [4.0 mg FD] / BEV 15 mg/kg | Quality of Life (QoL) | Nausea / vomiting | 2.4 score on a scale | Standard Deviation 6.3 |