Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Central Nervous System Depressants

Other Dietary Supplements

Amino Acids

Trastuzumab

Afatinib

Benzocaine

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tannic Acid

Tyrosine

Find maximum tolerated dose of the non-marketed substance:BIBW 2992 given orally with fixed weekly infusion doses of 2mg/kg Herceptin. Escalating doses of BIBW 2992 starting at 20mg daily.

Increased dose cohorts from low dose to MTD

BIBW 2992

Boehringer Ingelheim

Study to determine the Maximum Tolerated dose of BIBW 2992 given in combination with Herceptin®

Phase I Open Label Trial to Assess Safety of BIBW 2992 (Afatinib) in Combination With Herceptin® in Patients With HER2-positive Advanced Breast Cancer.

Phase I Open Label Trial to Assess Safety of BIBW 2992 in Combination With Herceptin® in Patients With HER2-positive Advanced Breast Cancer.

Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD). Important Limitations and Caveats are provided in the respective section.

The MTD was defined as the highest dose at which no more than 1 of 6 patients experienced DLT. It was determined using a standard 3 + 3 dose escalation cohort design. To confirm the MTD, the MTD cohort was to be expanded to 18 patients with no more than 3/18 patients experiencing a DLT. Please refer to CAVEATs and Limitations.

Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR).

Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) or not evaluable.

PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by central independent review according to the response evaluation criteria in solid tumors (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.

Pre-dose Concentrations of Afatinib in Plasma at Steady State on Days 8, 15 and 29 (Cpre,ss,8, Cpre,ss,15 and Cpre,ss,29) and Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss).

tmax,ss represents the time from dosing to the maximum concentration of afatinib in plasma at steady state

Pre-dose Concentrations of Herceptin in Plasma on Days 8, 15 and 29 (Cpre,8, Cpre,15 and Cpre,29) and Maximum Concentration of Herceptin in Plasma on Days 1, 15 and 29 (Cmax,1, Cmax,15 and Cmax,29).

Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression.

Afatinib 20mg + Herceptin

Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression.

Afatinib 30mg + Herceptin

Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression or lack of clinical benefit.

Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin (4 mg/kg single loading dose to be followed by 2 mg/kg/week i.v.) until disease progression or lack of clinical benefit.

Total

Age, Continuous

Sex: Female, Male

MTD was determined at 20mg afatinib when 1/6 pat. had DLT (3+3 design). Upon expansion of MTD cohort to 18 pat. recruitment was stopped when 4/13 pat. had DLT. No lower afatinib dose could be tested as 20mg was the lowest dose formulation available.

Boehringer Ingelheim Call Center

Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit. This group includes patients from the dose-escalation cohort and from the expansion cohort.

Patients received continuous daily dosing with Afatinib 30mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit.

Treated set (TS). TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib. 3 patients were excluded as they were not evaluable for determination of maximum tolerated dose.

Number of Participants With Dose Limiting Toxicities (DLT)

All patients received both Afatinib and Herceptin. Dose level 1 was continuous daily dosing with Afatinib 20mg tablets and once weekly an intravenous infusion of Herceptin. Dose level 2 was continuous daily dosing with Afatinib 30mg tablets and once weekly an intravenous infusion of Herceptin. Cycle length was 28 days.

TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib. 3 patients were excluded as they were not evaluable for determination of maximum tolerated dose.

Maximum Tolerated Dose (MTD) of Afatinib in Combination With Herceptin(R)

TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib.

Number of Patients With Objective Response (OR)

Complete Response

Partial Response

Stable Disease

Progressive Disease

Not evaluable

Number of Patients With Best Overall Response

Progression Free Survival (PFS)

Cpre,ss,8 (N=11)

Cpre,ss,15 (N=13)

Cpre,ss,29 (N=8)

Cmax,ss (N=10)

Patients received continuous daily dosing with Afatinib 20mg film-coated tablets and once weekly an intravenous infusion of Herceptin until disease progression or lack of clinical benefit.

Patients with no data available for the relevant parameter and dose were excluded from analysis.

Spots Global Cancer Trial Database for Phase I Open Label Trial to Assess Safety of BIBW 2992 (Afatinib) in Combination With Herceptin® in Patients With HER2-positive Advanced Breast Cancer.

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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