This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of rhuMab 2C4(Perjeta) and capecitabine (Xeloda) in participants with advanced solid tumors that have progressed during or after standard therapy, or for which no standard therapy is available. Participants will be enrolled and evaluated for dose-limiting toxicities (DLTs) in escalating-dose cohorts in order to determine the maximum tolerated dose (MTD).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Participants will receive capecitabine on Days 1 to 14 of each 3-week cycle as 825, 1000, or 1250 mg/m\^2 PO twice daily. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal.
Participants will receive rhuMab 2C4 on Day 1 of each 3-week cycle as 1050 mg via IV infusion. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal.
Unnamed facility
Barcelona, Spain
Unnamed facility
Manchester, United Kingdom
Maximum Tolerated Dose (MTD) of the Combination of Pertuzumab and Capecitabine
MTD was defined as the highest tolerated dose combination of capecitabine (825 mg, 1000 mg or 1250 mg) and pertuzumab, without causing Dose Limiting Toxicities (DLTs). DLTs were defined as follows: 1) Any non-hematological toxicity greater than or equal to (≥) Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management; 2) Grade 4 neutropenia lasting \> 7 days; 3) Febrile neutropenia; 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion; 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. Participants who withdrew from the study without completing the first treatment cycle for reasons other than DLT were not considered evaluable for DLT. MTD was measured in mg/m\^2.
Time frame: Cycle 1 (3 Weeks)
Percentage of Participants With DLTs
DLTs were defined as follows: 1)Any non-hematological toxicity greater than or equal to (≥) Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management; 2) Grade 4 neutropenia lasting \> 7 days; 3) Febrile neutropenia; 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion; 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. Participants who withdrew from the study without completing the first treatment cycle for reasons other than DLT were not considered evaluable for DLT.
Time frame: Cycle 1 (3 Weeks)
Plasma Half-Life (t1/2) of Pertuzumab
The biological half-life or terminal half-life of pertuzumab is the time in days it takes for it to lose half of its pharmacologic activity. t1/2 was measured in days.
Time frame: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and Predose on Days 8, 15 and 22
Maximum Plasma Concentration (Cmax) of Pertuzumab
Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and was measured as nanograms per milliliter (ng/mL).
Time frame: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22
Time to Maximum Plasma Concentration (Tmax) of Pertuzumab
Tmax is defined as the time after administration of a drug when the maximum plasma concentration is reached; when the rate of absorption equals the rate of elimination. Tmax was measured in days.
Time frame: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22
Area Under the Concentration Curve From Time Zero to Last Measurement (AUC 0-last) of Pertuzumab
The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-last is calculated from time 0 (prior to administration of medication) to last measured data point. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC was measured as ng\*day/mL.
Time frame: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22
AUC From Time Zero to Infinity (AUC 0-infinity) of Pertuzumab
The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as nanograms times days per milliliter (ng\*day/mL).
Time frame: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22
Apparent Volume of Distribution of Pertuzumab
The volume of distribution at steady state (Vss), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. Vss was measured in mL
Time frame: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22
Apparent Total Clearance of Pertuzumab
Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per day (mL/day).
Time frame: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22
Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine is a novel oral fluoropyrimidine carbamate that is preferentially converted to the cytotoxic moiety fluorouracil (5-fluorouracil; 5-FU) in target tumour tissue through a series of 3 metabolic steps through the intermediate metabolites 5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5-fluorouridine (5'-DFUR), and α-fluoro-β-alanine (FBAL). The biological half-life or terminal half-life is the time in days it takes for it to lose half of its pharmacologic activity.
Time frame: Day -7: Predose, 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours postdose; Cycle 1 Day 1: Predose, 0 and 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours Postdose
Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine is an oral fluoropyrimidine carbamate that is preferentially converted to the cytotoxic moiety 5-FU in target tumour tissue through a series of 3 metabolic steps through the intermediate metabolites 5'-DFCR, 5'-DFUR, and FBAL. Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as nanograms per milliliter (ng/mL).
Time frame: Day -7: Predose, 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours postdose; Cycle 1 Day 1: Predose, 0 and 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours Postdose
Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine is a novel oral fluoropyrimidine carbamate that is preferentially converted to the cytotoxic moiety fluorouracil (5-fluorouracil; 5-FU) in target tumour tissue through a series of 3 metabolic steps through the intermediate metabolites 5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5-fluorouridine (5'-DFUR), and α-fluoro-β-alanine (FBAL). Tmax is defined as the time after administration of a drug when the maximum plasma concentration is reached; when the rate of absorption equals the rate of elimination.
Time frame: Day -7: Predose, 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours postdose; Cycle 1 Day 1: Predose, 0 and 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours Postdose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.