| General information |
| Database: | DB00703 |
| Objective: | They conducted a phase Ib study to determine the maximumtolerated dose, the dose limiting toxicities (DLT), and pharmacokinetic (PK) interaction of docetaxel when administered in combination with pertuzumab. |
| Authors: | Attard G, et al |
| Title: | a phase Ib study of pertuzumab, a recombinant humanised antibody to human epidermal growth factor receptor 2, and docetaxel in patients with advanced solid tumours. |
| Journal: | Br J Cancer. |
| Year: | 2007 |
| PMID: | 18000498 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | pertuzumab
|
| Target: | Receptor proteintyrosine kinase erbB2
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | pertuzumab and docetaxel |
| Study Type: | a phase Ib, openlabel, twocenter study |
| Key Patients Feature: | Patients with histologically confirmed advanced solid tumoursthat had progressed during or after standard therapy or forwhich no standard therapy was available were eligible for thisstudy. A minimum of 4 weeks had to have passed from priortreatment with chemotherapy or radiotherapy. patients were alsorequired to have a life expectancy of at least 12 weeks and a EasternCooperative Oncology Group (ECOG) performance status of 0 or1. Other eligibility criteria included adequate bone marrow(absolute neutrophil count X1500 m 3, platelet countX100 000 m 3, and haemoglobin (Hgb) X9 g dl 1), renal (creatinine pupper normal limit or creatinine clearance ofX60 ml min 1), hepatic (bilirubin pupper normal limit andaspartate aminotransferase [AST], and alanine aminotransferase[ALT] p2.5 times the upper limits of normal) and cardiac(baseline left ventricular ejection fraction [LVEF] of X50%)function and a serum calcium within normal limits. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | two dose levels of docetaxel (60 and 75 mg m(2)) were explored in combination with a fixed dose of 1050 mg of pertuzumab; then two dose levels of docetaxel (75 and 100 mg m(2)) were explored in combination following a fixed dose of 420 mg of pertuzumab with a loading dose of 840 mg. Both drugs were administered intravenously every 3 weeks. |
| Primary End Point: | the maximumtolerated dose, the dose limiting toxicities (DLT), and pharmacokinetic (PK) interaction |
| Secondary End Point: | NA |
| Patients Number: | 19 |
| Trial Results |
| DLT_MTD: | The first two patients included in cohort 2 treated at75mgm2 of docetaxel and 1050 mg of pertuzumab developedDLTs, comprising of grade 4 febrile neutropaenia (neutrophilcount 0.4109 l1) on day 8 of the first cycle in one patient withgrade 3 diarrhoea on day 4 of the first cycle in another, lasting for 2days resolved without sequelae after treatment with loperamide, and grade 3 fatigue on day 6 in a second patient |
| Objective Response Rate: | NA |
| Disease Control Rate: | 0.824 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | No infusionrelated reactions were observed. Of the 17 patients with baseline and postbaseline cardiac function evaluations, three patients (18%) experienced an asymptomatic LVEF decrease from baseline of X10%: two patients in cohort 2A, one by 14% from 62 to 48% and the other from 61 to 48%, and one patient in cohort 1, from a baseline of 77% to a value of 53%. |
| Conclusions: | The recommendedphase II dose of this combination was docetaxel 75 mg m(2) and 420 mg pertuzumab following a loading dose of 840 mg. |