Clinical trial of PM01183 in combination with paclitaxel, with or without bevacizumab, in patients with solid tumors
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
69
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
Unnamed facility
New York, New York, United States
Unnamed facility
Madrid, Spain
Unnamed facility
Bellinzona, Switzerland
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)
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)
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)
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
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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)
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)
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)
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)