Back to resultsPhase I Study of Lurbinectedin (PM01183) in Combination With Paclitaxel, With or Without Bevacizumab, in Selected Advanced Solid Tumors
Primary Purpose
Breast Cancer, Ovarian Cancer, Gynecological Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PM01183 + paclitaxel +/- bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Voluntarily signed and dated written informed consent
- Age between 18 and 75 years old (both inclusive)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1
- Life expectancy ≥ 3 months.
Patients with a histologically/cytologically confirmed diagnosis of advanced and/or unresectable disease of any of the following tumors:
- Breast cancer
- Epithelial ovarian cancer or gynecological cancer
- Head and neck squamous cell carcinoma
- Non-small cell lung cancer
- Small cell lung cancer
- Platinum-refractory germ-cell tumors.
- 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:
- Less than three weeks since the last chemotherapy-containing regimen
- Less than three weeks since the last radiotherapy dose
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment
Arm Description
PM01183 + paclitaxel +/- bevacizumab
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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
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.
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01831089
Brief Title
Phase I Study of Lurbinectedin (PM01183) in Combination With Paclitaxel, With or Without Bevacizumab, in Selected Advanced Solid Tumors
Official Title
Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of Lurbinectedin (PM01183) in Combination With Weekly Paclitaxel, With or Without Bevacizumab, in Patients With Selected Advanced Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PharmaMar
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Ovarian Cancer, Gynecological Cancer, Head and Neck Carcinoma, Non-small Cell Lung Cancer, Small Cell Lung Cancer, Non-squamous Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
69 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm Description
PM01183 + paclitaxel +/- bevacizumab
Intervention Type
Drug
Intervention Name(s)
PM01183 + paclitaxel +/- bevacizumab
Intervention Description
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
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
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)
Title
Recommended Dose (RD)
Description
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)
Title
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Description
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)
Secondary Outcome Measure Information:
Title
Best Tumor Response
Description
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)
Title
Progression-free Survival
Description
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)
Title
Duration of Response (DR)
Description
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)
Title
Quality of Life (QoL)
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Voluntarily signed and dated written informed consent
Age between 18 and 75 years old (both inclusive)
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1
Life expectancy ≥ 3 months.
Patients with a histologically/cytologically confirmed diagnosis of advanced and/or unresectable disease of any of the following tumors:
Breast cancer
Epithelial ovarian cancer or gynecological cancer
Head and neck squamous cell carcinoma
Non-small cell lung cancer
Small cell lung cancer
Platinum-refractory germ-cell tumors.
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:
Less than three weeks since the last chemotherapy-containing regimen
Less than three weeks since the last radiotherapy dose
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
Facility Information:
City
New York
State/Province
New York
Country
United States
City
Madrid
Country
Spain
City
Bellinzona
Country
Switzerland
12. IPD Sharing Statement
Learn more about this trial
Phase I Study of Lurbinectedin (PM01183) in Combination With Paclitaxel, With or Without Bevacizumab, in Selected Advanced Solid Tumors
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