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

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: Drug: Cetuximab( erbitux®); Drug: Afatinib

• Registration Number: NCT02020577
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12
• Study First Submitted: 2013-12-19
• Study First Submitted QC: 2013-12-19
• Study First Posted: 2013-12-25
• Primary Completion: 2015-01
• Results First Submitted: 2016-01-14
• Results First Submitted QC: 2016-01-14
• Results First Posted: 2016-02-12
• Study Completion: 2016-04
• Status Verified: 2017-05
• Last Update Submitted: 2017-06-01
• Last Update Posted: 2017-06-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
combination arm	Cetuximab( erbitux®)	Patients to receive afatinib once daily plus weekly cetuximab infusion
combination arm	Afatinib	Patients to receive afatinib once daily plus weekly cetuximab infusion

Primary Outcome Measures

Name	Time	Method
MTD of Afatinib in Combination With Cetuximab Based on the Number of Patients With DLTs During the First Treatment Cycle (Afatinib).	First 21 days treatment cycle	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.
Dose Limiting Toxicities During Cycle 1	First 21-day 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
MTD of Afatinib in Combination With Cetuximab Based on the Number of Patients With DLTs During the First Treatment Cycle (Cetuximab).	First treatment cycle	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).

Secondary Outcome Measures

Name	Time	Method
Disease Control Rate	Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months	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
Recommended Phase II Dose Based on the Number of Patients With Dose Limiting Toxicity Events (Afatinib)	All treatment cycle (each treatment cycle of 21 days)	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	Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months	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.
Dose Limiting Toxicities During All Treatment Cycles	All treatment cycle (each treatment cycle of 21 days)	Number of patients with DLT occuring during all treatment cycle is presented
Recommended Phase II Dose Based on the Number of Patients With Dose Limiting Toxicity Events (Cetuximab)	All treatment cycle (each treatment cycle of 21 days)	MTD was deemed the recommended Phase II dose based on the number of patients with dose limiting toxicity events at all treatment cycles.
Objective Response	Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months	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.

Trial Locations

Locations (2)

1200.122.33001 Boehringer Ingelheim Investigational Site; 🇫🇷 Villejuif Cedex, France

1200.122.34001 Boehringer Ingelheim Investigational Site; 🇪🇸 Madrid, Spain