BIBW 2992 (Afatinib) and Vinorelbine in Japanese Patients With Advanced Solid Tumours

An Open-label Phase I Study of Once Daily Oral Treatment With BIBW 2992 in Combination With Weekly Vinorelbine Intravenous Injection in Japanese Patients With Advanced Solid Tumours

• To identify the Maximum Tolerated Dose (MTD) of afatinib in combination with vinorelbine i.v. by assessment of Dose Limiting Toxicities (DLT);
• To assess safety and anti-tumour efficacy and determine pharmacokinetic characteristics of afatinib and vinorelbine i.v.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: afatinib 20mg; Drug: afatinib 40mg; Drug: vinorelbine IV 25 or 20mg/m2

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chuo-ku, Osaka, Osaka, Japan
    • 1200.84.003 Boehringer Ingelheim Investigational Site
  • Kashiwa, Chiba, Japan
    • 1200.84.004 Boehringer Ingelheim Investigational Site
  • Nagoya, Aichi, Japan
    • 1200.84.001 Boehringer Ingelheim Investigational Site
  • Sakyo-ku, Kyoto, Kyoto, Japan
    • 1200.84.002 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Histologically confirmed diagnosis of malignancy that is advanced and for which standard therapies do not exist or are no longer effective.
• Life expectancy at least 12 weeks
• Eastern Cooperative Oncology Group Performance Status 0 or 1
• Adequate hepatic, renal, haematologic and other organ function
• Written informed consent

Exclusion criteria:

• Chemotherapy, immunotherapy, surgery and radiotherapy within the past 4 weeks
• Prior treatment with afatinib and or vinorelbine
• Clinically significant active infectious disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: afatinib and vinorelbine IV; patient to receive 20mg or 40mg of po daily afatinib in combination with vinorelbine IV	Drug: afatinib 20mg; patient to receive afatinib low dose po daily in combination with vinorelbine iv; Drug: afatinib 40mg; patient to receive afatinib high dose po daily in combination with vinorelbine iv; Drug: vinorelbine IV 25 or 20mg/m2; patient to receive standard dose vinorelbine once a week for four times per cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Dose Limiting Toxicities (DLTs) During 1st Course	DLTs and Maximum Tolerated Dose (MTD) of afatinib in combination with vinorelbine iv. (MTD = not determined)	during 1st course
Drug-related Adverse Events	Number of patients with drug-related adverse events	during the treatment period or up to 28 days after the completion of drug administration, up to 730 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCτ,ss for Afatinib	area under the plasma concentration-time curve following dose at steady state over the dosing interval τ	pre-dose, 1, 2, 3, 4, 6, 7hours, and 23hours55minutes after 7th or 14th or 21th dose (as "with Vinorelbine") and 20th dose (as "without Vinorelbine")
Cmax,ss for Afatinib	maximum measured plasma concentration at steady state	pre-dose, 1, 2, 3, 4, 6, 7hours, and 23hours55minutes after 7th or 14th or 21th dose (as "with Vinorelbine") and 20th dose (as "without Vinorelbine")
AUC0-∞ for Vinorelbine	area under the blood concentration-time curve of the analyte over the time interval from 0 extrapolated to infinity	predose, 10minutes, 0.5, 1, 4, 7 hours, 23hours55minutes after 2nd or 3rd or 4th dose (as "with afatinib") and 1st dose (as "without afatinib")
Cmax for Vinorelbine	maximum measured blood concentration	predose, 10minutes, 0.5, 1, 4, 7 hours, 23hours55minutes after 2nd or 3rd or 4th dose (as "with afatinib") and 1st dose (as "without afatinib")
Objective Tumour Response	According to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and assessed by CT or MRI: Complete Response (CR), disappearance of all target and non-target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."	Pre-treatment, every 8 weeks after start of study treatment, end of treatment

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2010
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: October 4, 2010
• First Submitted That Met QC Criteria: October 4, 2010
• First Posted (Estimated): October 5, 2010

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Vinorelbine; Afatinib
• Other Study ID Numbers: 1200.84

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datatransparency