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

Phase 1

Completed

• Conditions: Breast Neoplasms; Stomach Neoplasms
• Interventions: Drug: trastuzumab; Drug: Herceptin; Drug: afatinib

• Registration Number: NCT01649271
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-07-23
• Study First Submitted: 2012-07-23
• Study First Submitted QC: 2012-07-23
• Study First Posted: 2012-07-25
• Primary Completion: 2016-06-23
• Study Completion: 2016-06-23
• Results First Submitted: 2017-06-19
• Results First Submitted QC: 2017-06-19
• Results First Posted: 2017-11-06
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-21
• Last Update Posted: 2025-02-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Phase Ib	trastuzumab	afatinib at MTD level with 3-weekly trastuzumab
Phase Ia, group 1	Herceptin	afatinib escalating dose with 3-weekly trastuzumab
Phase Ia, group 2	Herceptin	afatinib at MTD dose with weekly trastuzumab
Phase Ia, group 1	afatinib	afatinib escalating dose with 3-weekly trastuzumab
Phase Ib	afatinib	afatinib at MTD level with 3-weekly trastuzumab
Phase Ia, group 2	afatinib	afatinib at MTD dose with weekly trastuzumab

Primary Outcome Measures

Name	Time	Method
MTD of Afatinib in Combination With Trastuzumab 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 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.
Dose Limiting Toxicities During cycle1	First 21-day treatment cycle	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.

Secondary Outcome Measures

Name	Time	Method
Best Overall Response (BOR)	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 End of Treatment (EOT); up to 33 months	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	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 33 months	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	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 33 months	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.

Trial Locations

Locations (3)

INS Claudius Regaud; 🇫🇷 Toulouse, France

CTR Georges-François Leclerc; 🇫🇷 Dijon, France

CTR René Gauducheau; 🇫🇷 Saint Herblain, France