A Phase Ib, Open-label, Multicenter Study of the Safety and PK of the Combination of rhuMAb2c4 (Omnitarg), a Recombinant Humanized Antibody to HER2, and Capecitabine (Xeloda) in Patients With Advanced Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase Ib, Open-Label, Multicenter Study of the Safety and Pharmacokinetics of the Combination of RhuMab 2C4 (Omnitarg), a Recombinant Humanized Antibody to HER2, and Capecitabine (Xeloda) in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02494596
• Other study ID #: BO17003
• Status: Completed
• Phase: Phase 1
• First received: July 8, 2015
• Last updated: October 12, 2015
• Start date: January 2004
• Est. completion date: September 2005

Study information

• Verified date: October 2015
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: September 2005
• Est. primary completion date: September 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults at least 18 years of age

• Easter Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Life expectancy at least 12 weeks

• Locally advanced or metastatic solid tumor with at least 1 measurable lesion, which has progressed during/after standard therapy

• Human epidermal growth factor receptor 2 (HER2)-negative among participants with breast cancer

• Negative pregnancy test or use of an adequate contraceptive method among women of childbearing potential

• Adequate hematologic, hepatic, and renal function

Exclusion Criteria:

• Clinical evidence of central nervous system (CNS) metastases

• Prior chemotherapy, radiotherapy, or immunotherapy within 4 weeks, or hormone therapy within 2 weeks of study Day 1

• History of palmar plantar syndrome Grade 2 or worse, or any unresolved residual chemotherapy effects

• Prior HER2-active agents, continuous intravenous (IV) 5-fluorouracil, capecitabine, or other fluoropyrimidine

• Any investigational agent within 28 days of study start

• Prior cumulative doxorubicin dose greater than (>) 360 mg/m^2 or equivalent

• Significant cardiovascular disease

• Active/uncontrolled concurrent illness or infection-

• Major surgery or trauma within 4 weeks of study Day 1

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumor

Intervention

Drug:
• Capecitabine
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.
• RhuMab 2C4
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Cycle 1 (3 Weeks)	No
Secondary	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.	Cycle 1 (3 Weeks)	No
Secondary	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.	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	No
Secondary	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).	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	No
Secondary	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.	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	No
Secondary	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.	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	No
Secondary	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).	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	No
Secondary	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	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	No
Secondary	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).	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	No
Secondary	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 a-fluoro-ß-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.	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	No
Secondary	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).	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	No
Secondary	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 a-fluoro-ß-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.	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	No