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Afatinib as Cancer Therapy for Exocrine Pancreatic Tumours

NCT01728818 · Status: UNKNOWN · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 119

Last updated 2017-07-19

No results posted yet for this study

Summary

Single-agent gemcitabine is currently still regarded as one international standard of care for patients with advanced pancreatic cancer (Burris 1997 \[4\]). The oral EGFR tyrosine kinase inhibitor erlotinib received EMEA-approval for the treatment of patients with metastatic pancreatic cancer in January 2007.

In the pivotal phase III trial, the combination of gemcitabine plus erlotinib was associated with a statistically significant prolongation of OS (compared to single-agent gemcitabine), however, the absolute survival benefit was - for the overall study population - clinically moderate (median OS: 6.24 vs 5.91 months, 1-year OS rate: 23% vs 17%; HR = 0.82, p=0.038) (Moore 2007 \[19\]).

The recently presented FOLFIRINOX regimen shows enhanced activity in metastatic pancreatic cancer patients. This regimen is, however, limited to patients with good performance status (ECOG 0-1), no major comorbidity, age \<75 years, and bilirubin \<1.5 ULN (Conroy 2011 \[6\]). The majority of pancreatic cancer patients will therefore not be treated with this regimen.

Accordingly, novel treatment concepts are urgently needed in pancreatic cancer and pre-clinical data indicate an important role of the EGFR1/erbB2 receptor signalling in the pathogenesis of pancreatic adenocarcinoma (Yeh 2007 \[24\]). A recent publication (Larbouret 2010 \[16\]) indicates that the combination of cetuximab and trastuzumab induced superior antitumour activity in human pancreatic carcinoma xenografts compared to gemcitabine alone (see also Larbouret 2007 \[15\]). Furthermore, synergistic antitumour activity was observed when monoclonal antibodies directed against the EGFR1 and erbB2 were combined (Ben-Kasus 2009 \[3\]). Based on these data, there is a good rationale to further investigate the combined inhibition of the erbB family in pancreatic cancer patients.

Afatinib (BIBW 2992) is a novel irreversible EGFR1- and HER2 and HER4 inhibitor that is applied orally. The purpose of the present trial is to investigate the erbB family inhibition by afatinib in patients with metastatic pancreatic cancer.

In the planned trial, afatinib will be applied at the dose (40 mg/day) that was chosen for the randomised phase III trial (LUX 5 study) that investigates afatinib plus weekly paclitaxel (80mg/m2).

Presently there is also a phase I study ongoing that investigates the combination of afatinib with gemcitabine (ClinicalTrials.gov Identifier: NCT01251653 U10-2249-02 ). Possibly the data will be available once the study is ready to start. Otherwise a modification of the regimen will be planned once the respective data will be available.

In this trial, we integrate a translational project which may allow the identification of patients that primarily benefit from this novel treatment approach. The availability of tumour tissue- and blood samples from each patient is therefore an important inclusion criterion.

A 2:1 randomisation is chosen favouring the experimental arm since a large body of data is available on gemcitabine alone and since sufficient efficacy and toxicity data shall be gained in the experimental arm. In addition, the patients' motivation to take part in the trial will be greatly enhanced by a greater chance to receive the experimental agent.

Conditions

  • Focus of Study Instead

Interventions

DRUG

Gemcitabine

1000 mg/m² d1,8,15 q4weeks

DRUG

Afatinib

40mg flat dose, po, once daily

DRUG

Gemcitabine

1000 mg/m², d1,8,15 q4weeks

Sponsors & Collaborators

Principal Investigators

  • Volker Heinemann, Professor · Medical Department III and Comprehensive Cancer Center

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2013-04-30
Primary Completion
2017-01-31
Completion
2018-01-31

Countries

  • Germany

Study Locations

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Entities

Drugs
Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01728818 on ClinicalTrials.gov