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

NCT01649271 | Completed Phase 1 Results

• 2 other identifiers: 1200.1342012-001753-10
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

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.

Conditions

Breast Neoplasms; Stomach Neoplasms

Outcome Measures

Primary Outcomes (2)

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

  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.

  First 21 days treatment cycle

• Dose Limiting Toxicities During cycle1

  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.

  First 21-day treatment cycle

Secondary Outcomes (3)

• 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

• 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

• 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

Study Arms (3)

Phase Ia, group 1

EXPERIMENTAL

afatinib escalating dose with 3-weekly trastuzumab

Drug: Herceptin; Drug: afatinib

Phase Ia, group 2

EXPERIMENTAL

afatinib at MTD dose with weekly trastuzumab

Drug: afatinib; Drug: Herceptin

Phase Ib

EXPERIMENTAL

afatinib at MTD level with 3-weekly trastuzumab

Drug: trastuzumab; Drug: afatinib

Interventions

Herceptin DRUG

3-weekly

Phase Ia, group 1

afatinib DRUG

at MTD level

Phase Ia, group 2

trastuzumab DRUG

3-weekly

Phase Ib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

CTR Georges-François Leclerc

Dijon, 21079, France

Location

CTR René Gauducheau

Saint-Herblain, 44805, France

Location

INS Claudius Regaud

Toulouse, 31059, France

Location

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms; Stomach Neoplasms

Interventions

Trastuzumab; Afatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

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.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: July 25, 2012
• Study Start: July 23, 2012
• Primary Completion: June 23, 2016
• Study Completion: June 23, 2016
• Last Updated: February 11, 2025
• Results First Posted: November 6, 2017

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)