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OpenTrials
Completed

NCT Number: NCT01649271

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

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.

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Key information

Conditions

Breast Neoplasms Breast Diseases Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases Stomach Diseases Stomach Neoplasms

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

CTR Georges-François Leclerc, Dijon, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients aged 18 years and older
  • Patients with cancers overexpressing HER2 by Immunohistochemistry test( IHC) 3+ and/or IHC 2+ with positive gene amplification by FISH (confirmation on archived tissue needed)
  • Written informed consent that is consistent with ICH-GCP guidelines.
  • Patients must be eligible for treatment with trastuzumab.
  • Patients must have adequate organ function (kidney, liver, bone marrow, cardiac)
  • Eastern Cooperative Oncology Group (ECOG) = 0 or 1.
  • Measurable disease according to RECIST 1.1 (Phase Ib).

Exclusion criteria

  • Active brain metastases.
  • Prior treatment with erbB family targeting therapies within the past four weeks before start of therapy or concomitantly with the trial other than trastuzumab and/or lapatinib.
  • Patients having more than 2 lines of chemotherapy for the treatment of metastatic breast cancer (Phase Ib).

Treatment and study plan

Herceptin

Drug

3-weekly

afatinib

Drug

at MTD level

Trastuzumab

Drug

3-weekly

Primary outcomes

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

    Time frame: 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.

  2. Dose Limiting Toxicities During cycle1

    Time frame: 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 outcomes

  1. Best Overall Response (BOR)

    Time frame: 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.

  2. Objective Response

    Time frame: 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.

  3. Clinical Benefit

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

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.

Important dates

Study start
2012
Primary completion
2016
Study completion
2016
First posted
Jul 25, 2012
Registry last updated
Feb 11, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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