Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Digestive System Diseases

Rare Diseases

Breast Neoplasms

Stomach Neoplasms

Breast Diseases

Skin Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Trastuzumab

Afatinib

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

afatinib escalating dose with 3-weekly trastuzumab

afatinib at MTD dose with weekly trastuzumab

afatinib at MTD level with 3-weekly trastuzumab

Herceptin

afatinib

trastuzumab

Boehringer Ingelheim

The aim of the study is to determine the Maximum Tolerated Dose (MTD) of afatinib in combination with 3-weekly trastuzumab in HER2 overexpressing cancer and to assess the efficacy of afatinib given at the MTD dosage, with 3-weekly trastuzumab in HER2 overexpressing metastatic breast cancer.

Phase I Trial of Afatinib and Trastuzumab in HER2 Overexpressing Cancer.

Phase I Trial of Afatinib in Combination With 3 Weekly Trastuzumab in Patients With Tumours Overexpressing HER2. Once the MTD of Afatinib With 3 Weekly Trastuzumab Was Established the Safety of This Dose Will be Assessed Also in Combination With Weekly Trastuzumab.

Maximum Tolerated Dose (MTD) of Afatinib in combination with trastuzumab based on the number of patients with dose limiting toxicity (DLT) during the first treatment cycle (Dose escalation part). The MTD was defined as the highest dose studied at which the incidence of a DLT was less than 17% (i.e. 1/6 patients) during the first cycle.

One patient in the Afa30+Trast8 cohort developed tumour lysis syndrome during the first course of treatment and was therefore not evaluable for the primary endpoint.

Number of Patients With Dose Limiting Toxicity (DLT) occurring during Cycle 1 based on the investigator assessment.

One patient in the Afa30+Trast8 cohort developed tumour lysis syndrome during the first course of treatment and was therefore not evaluable for the primary endpoint.

BOR represents the best response a patient had during their time in study from start of treatment until progression, the last evaluable assessment in absence of progression or start of subsequent anticancer therapy. For patients that died, BOR was to be calculated based on data up to last evaluable RECIST,v1.1 assessment prior to death. Death did not contribute as PD for BOR. As per RECIST v1.1 for target lesions (TL) \& assessed by MRI: CR: Disappearance of all TL,all non-TL, \& no new lesion. Any pathological lymph nodes must have had reduction in the short axis to \<10 mm. PR: At least 30% decrease in sum of the longest diameter (SLD) of TL taking as reference the baseline SLD. PD: At least a 20% increase in SLD of TL taking as reference the smallest SLD recorded since treatment started, together with an absolute increase in SLD of at least 5mm. SD: Neither sufficient shrinkage to qualify for PR, taking as reference the baseline SLD, nor sufficient increase to qualify for PD.

Objective Response (OR) was defined as best overall response of complete response (CR) or partial response (PR), where best overall response was determined according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 from first administration of study medication until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy. As Per RECIST v1.1 for target lesions (TL) \& assessed by MRI: CR: Disappearance of all TL,all non-TL, \& no new lesion. Any pathological lymph nodes must have had reduction in the short axis to \<10 mm. PR: At least 30% decrease in sum of the longest diameter (SLD) of TL taking as reference the baseline SLD.

Clinical benefit was defined as best overall response of CR or PR or stable disease (SD) where best overall response is defined according to RECIST version 1.1 from first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy.

As Per RECIST v1.1 for target lesions (TL) \& assessed by MRI: CR: Disappearance of all TL,all non-TL, \& no new lesion. Any pathological lymph nodes must have had reduction in the short axis to \<10 mm. PR: At least 30% decrease in sum of the longest diameter (SLD) of TL taking as reference the baseline SLD. SD: Neither sufficient shrinkage to qualify for PR, taking as reference the baseline SLD, nor sufficient increase to qualify for PD.

In each 21 day treatment cycle, patients were administered orally 20 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.

Phase Ia: Afatinib 20mg+Trastuzumab 8 mg/kg

In each 21 day treatment cycle, patients were administered orally 30 mg afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.

Phase Ia: Afatinib 30mg+Trastuzumab 8 mg/kg

Total

Age, Continuous

Sex: Female, Male

Treated Set (TS): This patient set includes all patients who were documented to have taken at least one dose of study medication.

Phase Ib was not started due to the discontinuation of afatinib development in HER2 overexpressing metastatic breast cancer and also the availability of other approved efficacious treatment options.Thus the results are not provided for Phase Ib.

Boehringer Ingelheim, Call Center

In each 21 day treatment cycle, patients were administered orally afatinib tablet from Day 2 continuous daily administration in combination with trastuzumab. An initial loading dose of trastuzumab 8 mg/kg was administered via intravenous infusion at Day1 Cycle1, followed by trastuzumab 6 mg/kg every 3 weeks. Trastuzumab intravenous infusion, 90 minutes, infusion duration could be reduced to 30 minutes if well tolerated.

Phase Ia: Afatinib +Trastuzumab 8 mg/kg

Treated set: This analysis set includes all patients who were documented to have taken at least one dose of study medication.

MTD of Afatinib in Combination With Trastuzumab Based on the Number of Patients With DLTs During the First Treatment Cycle (Afatinib).

Dose Limiting Toxicities During cycle1

Complete Response (CR)

Partial Response (PR)

Stable Disease (SD)

Progressive Disease (PD)

Missing

Not Evaluable

Treated set

Missing: First image time point not reached before discontinuation.

Spots Global Cancer Trial Database for Phase I Trial of Afatinib and Trastuzumab in HER2 Overexpressing Cancer.

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Study Description

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