Study to Determine the Maximum Tolerated Dose of BIBW 2992 (Afatinib) When Combined With Cisplatin/Paclitaxel or Cisplatin/5-FU in Patients With Advanced Solid Tumours

NCT00716417 | Completed Phase 1 Results

• 2 other identifiers: 1200.372008-002613-43
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 3

Brief Summary

Study to determine the maximum tolerated dose of BIBW 2992 when combined with backbone chemotherapies consisting in cisplatin plus paclitaxel or cisplatin plus 5 FU. The overall safety, the pharmacokinetics and the anti-tumour efficacy will also be assessed.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

  Number of participants with DLT in the first cycle (21 days) for the determination of the MTD.

  21 days

• Maximum Tolerated Dose (MTD) for Regimen A and Regimen B

  The MTD was determined using a standard 3 +3 dose escalation cohort design. The sample size and the number of patients who receive each dose in this design depends on the frequency of DLT at each dose level in cycle 1.

  21 days

Secondary Outcomes (2)

• Number of Patients With Objective Response

  Tumor assessment were performed at screening and every 2nd cycle until end of follow up (=end of treatment + 30 days +/- 7 days)

• Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss)

  0.05hours (h) before administration and 1h, 2h, 2h 55 minutes (min), 4h, 4h 30min, 5h, 6h, 8h, 10h, 24h, 48h, 216h, 480h after administration

Study Arms (2)

A. BIBW 2992-cisplatin-paclitaxel

EXPERIMENTAL

daily oral dose of BIBW 2992 combined with 3-weekly infusion of cisplatin-paclitaxel

Drug: BIBW 2992

B. BIBW 2992-cisplatin-5FU

EXPERIMENTAL

daily oral dose of BIBW 2992 combined with 3-weekly infusion of cisplatin-5FU

Drug: BIBW 2992

Interventions

BIBW 2992 DRUG

In each arm, BIBW 2992 dose will be escalated to determine MTD. Starting dose will be 20mg daily followed by 40 mg (with the option of an intermediary dose of 30 mg) then 50mg daily. Dose escalation will stop at 50 mg. No intra patient dose escalation.

B. BIBW 2992-cisplatin-5FU

Eligibility Criteria

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

You may qualify if:

• Patients with histologically or cytologically confirmed diagnosis of non resectable and / or metastatic cancer, preferably squamous cell carcinomas of head and neck, oesophagus, lung or cervix
• Indication for a standard treatment with either cisplatin plus paclitaxel or cisplatin plus 5 FU as judged by the investigator
• Age 18 years or older.
• Life expectancy of at least three (3) months.
• Written informed consent that is consistent with ICH-GCP guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance score less or equal 2.
• Patients must have recovered from any therapy-related toxicity from previous chemo-, hormone-, immuno-, or radiotherapies.
• Patients recovered from previous surgery.

You may not qualify if:

• Active infectious disease.
• Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea.
• Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
• Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least four (4) weeks, no history of cerebral oedema or bleeding in the past four (4) weeks and no requirement for steroids or anti-epileptic therapy.
• Cardiac left ventricular function with resting ejection fraction less than 50%
• Absolute neutrophil count (ANC) less than 1500 / mm3.
• Platelets count less than 100 000/mm3.
• Bilirubin more than 1.5 x upper limit of institutional norm.
• Aspartate amino transferase (AST) or alanine amino transferase (ALT) more than 3 x upper limit of institutional norm.
• Serum creatinine more than 1.5 x upper limit of institutional norm.
• Women and men sexually active and unwilling to use a medically acceptable method of contraception.
• Pregnancy or breast-feeding.
• Treatment with other investigational drugs; chemotherapy, immunotherapy, or radiotherapy or participation in another clinical study with anti-cancer therapy within the past 4 weeks before start of therapy or concomitantly with this study.
• Treatment with an EGFR- or HER2 inhibiting drug within the past four weeks before start of therapy or concomitantly with this study (2 weeks for trastuzumab).
• Patients unable to comply with the protocol.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

1200.37.3202 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1200.37.3201 Boehringer Ingelheim Investigational Site

Edegem, Belgium

Location

1200.37.3203 Boehringer Ingelheim Investigational Site

Ghent, Belgium

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Afatinib

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

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

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
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2008
• First Posted: July 16, 2008
• Study Start: July 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: August 5, 2025
• Results First Posted: October 16, 2013

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• Access Criteria: For study documents - upon signing of a "Document Sharing Agreement". For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Locations

BE (3)