Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Cetuximab

Afatinib

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients to receive afatinib once daily plus weekly cetuximab infusion

Cetuximab( erbitux®)

Boehringer Ingelheim

The trial is divided in two parts, Part A and Part B. Part A will involve dose-finding of dose-limiting toxicity (DLT) and MTD in patients with advanced solid tumours. Part B will involve expansion of the MTD to 3 cohorts including non-small cell lung cancer squamous histology, recurrent/ metastatic squamous cell carcinoma of head and neck and other advanced solid tumours (except sarcomas).

Trial of Afatinib (BIBW 2992) + Cetuximab in Advanced Solid Tumours

A Phase Ib Dose Escalation Study of Afatinib in Combination With Cetuximab in Patients With Advanced Solid Tumours

Maximum Tolerated Dose (MTD) of Afatinib in combination with cetuximab based on the number of patients with dose limiting toxicity (DLT) during the first treatment cycle (Dose escalation part). The MTD is defined as the highest dose level at which less than 33% of the patients experience DLT in first treatment cycle.

Number of Patients With Dose Limiting Toxicity (DLT) Occurring during Cycle 1. The following drug related AEs qualified as DLT:

1) CTCAE Grade ≥2 decrease in cardiac left ventricular function 2) CTCAE Grade 2 diarrhoea lasting for ≥7 days, despite appropriate use of standard antidiarrheal therapy based on Protocol Amendment 1 dated 22 Oct 2013 3) CTCAE Grade ≥3 diarrhoea despite appropriate use of standard anti-diarrheal therapy for at least 2 days. 4) CTCAE Grade ≥3 nausea and/or vomiting despite appropriate use of standard anti-emetics for at least 3 days 5) CTCAE Grade ≥3 rash despite standard medical management. 6) CTCAE Grade ≥3 fatigue lasting more than 7 days. 7) All other AEs of CTCAE Grade ≥3 (except alopecia and allergic reaction) that led to an interruption of afatinib and/or cetuximab dosing for more than 14 days until recovery to baseline or Grade 1, whichever was higher. 8) CTCAE Grade 4 hypomagnesemia or Grade 3 hypomagnesemia with clinically-significant sequelae

Maximum Tolerated Dose (MTD) of Afatinib in combination with cetuximab based on the number of patients with DLTs during the first treatment cycle (Dose escalation part).

Number of patients with DLT occuring during all treatment cycle is presented

MTD was deemed the recommended Phase II dose based on the number of patients with dose limiting toxicity events at all treatment cycles.

Best overall response (according to RECIST version 1.1) was defined as the best response recorded at any time from the first administration of afatinib or cetuximab to the End of Treatment (EOT).

As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI:

Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

Objective response was defined as the proportion of patients with measurable disease having at least a best overall response of complete response (CR) or partial response (PR), according to RECIST version 1.1.

As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI:

Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

For patients with measurable disease, disease control was defined as the proportion of patients having at least a best overall response of CR, PR or stable disease (SD).

As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI:

Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression

In each 21 day treatment cycle, patients were administered 30 mg Film-coated tablet daily afatinib in combination with cetuximab. An initial loading dose of cetuximab 400mg/m2 was administered intravenously at Day1 Cycle1, followed by cetuximab 250mg/m² weekly dose.

Afatinib 30mg+Cetuximab 250 mg/m²

In each 21 day treatment cycle, patient were administered 40 mg Film-coated tablet daily afatinib in combination with cetuximab. An initial loading dose of cetuximab 400 mg/m2 was administered intravenously at Day1 Cycle1, followed by cetuximab 250mg/m² weekly dose.

Afatinib 40mg+Cetuximab 250 mg/m²

Patients who were administered Afatinib 30mg+cetuximab 250 mg/m² plus the patients who were administered Afatinib 40mg+cetuximab 250 mg/m².

All Patients

Total

Age, Continuous

Sex: Female, Male

Treated set: This patient set includes all patients enrolled in the trial who were documented to have taken at least one dose of study medication.

Boehringer Ingelheim, Call Center

Dose finding cohort treated set: This patient set includes all patients enrolled in part A of the trial who were documented to have taken at least one dose of study medication.

Spots Global Cancer Trial Database for cetuximab( erbitux®)