Afatinib as Cancer Therapy for Exocrine Pancreatic Tumours (ACCEPT)
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|ClinicalTrials.gov Identifier: NCT01728818|
Recruitment Status : Unknown
Verified July 2017 by PD Dr. med. Volker Heinemann, Ludwig-Maximilians - University of Munich.
Recruitment status was: Active, not recruiting
First Posted : November 20, 2012
Last Update Posted : July 19, 2017
Single-agent gemcitabine is currently still regarded as one international standard of care for patients with advanced pancreatic cancer (Burris 1997 ). 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 ).
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 ). 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 ). A recent publication (Larbouret 2010 ) 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 ). Furthermore, synergistic antitumour activity was observed when monoclonal antibodies directed against the EGFR1 and erbB2 were combined (Ben-Kasus 2009 ). 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.
|Condition or disease||Intervention/treatment||Phase|
|Focus of Study Instead||Drug: Gemcitabine Drug: Afatinib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||119 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Gemcitabine in Combination With the Oral Irreversible ErbB Inhibitor Afatinib Versus Gemcitabine Alone in Patients With Metastatic Pancreatic Cancer: an Explorative Randomized Phase II Trial|
|Study Start Date :||April 2013|
|Actual Primary Completion Date :||January 2017|
|Estimated Study Completion Date :||January 2018|
|Experimental: Arm A||
1000 mg/m² d1,8,15 q4weeks
40mg flat dose, po, once daily
|Active Comparator: Arm B||
1000 mg/m², d1,8,15 q4weeks
- Overall Survial [ Time Frame: approximately 36 months ]Overall Survival
- PFS [ Time Frame: Approximately 36 months ]Progression-free survival (PFS)
- Duration of response [ Time Frame: approximately 36 months ]Duration of response
- 1 Year Survial [ Time Frame: approximately 36 months ]One Year Survial
- CA19-9 [ Time Frame: approximately 36 months ]Biochemical tumour marker response (serum CA 19- 9)
- Quality of life [ Time Frame: approximately 36 months ]Evaluation of Quality of life with EORTC QLQ C-30 Questionaire
- Toxicity [ Time Frame: approximately 36 months ]Toxicity (NCI CTC-AE v4.0)
- Staging [ Time Frame: approximately 36 months ]All tumour assessments will be done by CT or MRI at 2-months intervals. One method of imaging will be kept consistent for each individual patient. All comparisons will be refrenced to baseline imaging (performed within 4 weeks prior to randomisation).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01728818
|University of Munich|
|Munich, Germany, 81377|
|Principal Investigator:||Volker Heinemann, Professor||Medical Department III and Comprehensive Cancer Center|