Focus of Study InsteadPhase 2ACCEPTNCT01728818
Afatinib as Cancer Therapy for Exocrine Pancreatic Tumours
A Phase 2 study testing Gemcitabine and Afatinib in people with Focus of Study Instead, run by PD Dr. med. Volker Heinemann at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Focus of Study Instead
- What is being tested?
- Gemcitabine and Afatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2013to Jan 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent in advance of any study-specific procedure
- Histologically (not cytologically) confirmed diagnosis of metastatic pancreatic adenocarcinoma (stage IV according to UICC 2009 classification: each T, each N, M1)
- Availability of tumour samples
- Informed consent that tumour- and blood samples are centrally collected and will serve for translational analyses according to the study protocol.
- Age >= 18 years
- ECOG 0-1
Show all 13Show fewer
- Life expectancy at least 3 months
- No option for surgical resection or radiation in curative intent
- At least one measurable tumour lesion (CT-scan or MRI) according to RECIST Version 1.1
- Possibility of long-term follow-up
- Negative pregnancy test in fertile females
- Given legal capacity of the patient
- Adequate hepatic, renal and bone marrow function
Who cannot join
- Evidence of weight loss > 15% within one month
- Active brain metastases (stable for <28 days, symptomatic, or requiring concurrent steroids) or leptomeningeal disease. Patients who have received prior whole brain irradiation and whose brain metastases are stable according to the criteria above will not be excluded
- Previous gemcitabine treatment is allowed only if applied as monotherapy in the adjuvant setting and if the adjuvant single-agent gemcitabine chemotherapy was terminated at least 6 months before study entry
- Previous systemic treatment with chemotherapy or radiotherapy for locally advanced, non resectable or metastatic pancreatic cancer
- Radiotherapy within four weeks prior to randomization or radiation of target lesions
- Prior treatment with EGFR targeting therapies or treatment with EGFR- or HER2 inhibiting drugs within the past 4 weeks before start of therapy or concomitantly with this trial
Show all 25Show fewer
- Hypersensitivity to afatinib or to gemcitabine or to any of the excipients or to compounds with similar chemical or biologic composition
- Contraindications against the use of gemcitabine
- Severe renal insufficiency (baseline creatinine clearance < 30 ml/mi)
- LDH elevated by > 2.5 ULN
- Severe hepatic dysfunction
- Any disease e. g. active infection, uncontrolled hypertension, clinically significant cardiovascular disease for example CVA (<= 6 months before study start), myocardial infarction (<= 6 months before study start), unstable angina, NYHA >= grade 2 CHF, arrhythmia requiring medication, metabolic dysfunction giving reasonable suspicion of a disease or condition that contra-indicates the use of the study drugs or puts the patient at high risk for treatment-related complications
- Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption or CTC grade > 2 diarrhoea of any aetiology
- Pregnant or lactating females, non-effective contraception in men and women of childbearing potential (an effective contraceptive measure has a Pearl Index < 1)
- Any major surgery within the last 2 weeks before study entry
- Chemo- or immunotherapy within the past 4 weeks
- Treatment with an investigational drug in another clinical study within the past 28 days prior to the start of therapy or concomitantly with this study
- Any persisting toxicities which are deemed to be clinically significant from the previous therapy
- Patients with pre-existing interstitital lung disease
- Psychological, familial, social or geographic conditions that may prevent an adequate compliance with the study protocol
- Known or suspected alcohol- or drug abuse
- Patients unable to comply with the protocol
- Known hepatitis B infection, known hepatitis C infection or HIV carrier
- Requirement for treatment with any of the prohibited concomitant medications
- Any other malignancies within the last 5 years before study start, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer
Trial locations and contacts
1 site in 1 country.
About this study
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
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]).
Read more
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
- Being tested
- Gemcitabine, Afatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
1000 mg/m² d1,8,15 q4weeks
AfatinibDrug
40mg flat dose, po, once daily
GemcitabineDrug
1000 mg/m², d1,8,15 q4weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Not described Receives: Drug: Gemcitabine; Drug: Afatinib |
| Arm B | Active comparator | Not described Receives: Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survial
Overall Survival
Measured: approximately 36 months
Secondary outcomes (7)
PFS
Progression-free survival (PFS)
Measured: Approximately 36 months
Duration of response
Duration of response
Measured: approximately 36 months
1 Year Survial
One Year Survial
Measured: approximately 36 months
CA19-9
Biochemical tumour marker response (serum CA 19- 9)
Measured: approximately 36 months
Quality of life
Evaluation of Quality of life with EORTC QLQ C-30 Questionaire
Measured: approximately 36 months
Toxicity
Toxicity (NCI CTC-AE v4.0)
Measured: approximately 36 months
Staging
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).
Measured: approximately 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2012 (estimated)
- Study startApr 2013
- Primary completionJan 2017
- Study completionJan 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Focus of Study InsteadStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- PD Dr. med. Volker Heinemann
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Responsible party
- Sponsor-investigator, PD Dr. med. Volker Heinemann, Ludwig-Maximilians - University of Munich
- Investigators
- Volker Heinemann, Professor, Principal investigator, Medical Department III and Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01728818
- Sponsor's protocol ID
- 2011-004063-77
- Acronym
- ACCEPT
- Status last verified
- Jul 2017
- First submitted
- 5 Jul 2012
- Last updated
- 19 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Weiss L, Heinemann V, Fischer LE, Gieseler F, Hoehler T, Mayerle J, Quietzsch D, Reinacher-Schick A, Schenk M, Seipelt G, Siveke JT, Stahl M, Vehling-Kaiser U, Waldschmidt DT, Dorman K, Zhang D, Westphalen CB, von Bergwelt-Baildon M, Boeck S, Haas M. Three-month life expectancy as inclusion criterion for clinical trials in advanced pancreatic cancer: is it really a valid tool for patient selection? Clin Transl Oncol. 2024 May;26(5):1268-1272. doi: 10.1007/s12094-023-03323-1. Epub 2023 Oct 4.
PubMed 37794220Haas M, Waldschmidt DT, Stahl M, Reinacher-Schick A, Freiberg-Richter J, Fischer von Weikersthal L, Kaiser F, Kanzler S, Frickhofen N, Seufferlein T, Dechow T, Mahlberg R, Malfertheiner P, Illerhaus G, Kubicka S, Abdul-Ahad A, Snijder R, Kruger S, Westphalen CB, Held S, von Bergwelt-Baildon M, Boeck S, Heinemann V. Afatinib plus gemcitabine versus gemcitabine alone as first-line treatment of metastatic pancreatic cancer: The randomised, open-label phase II ACCEPT study of the Arbeitsgemeinschaft Internistische Onkologie with an integrated analysis of the 'burden of therapy' method. Eur J Cancer. 2021 Mar;146:95-106. doi: 10.1016/j.ejca.2020.12.029. Epub 2021 Feb 12.
PubMed 33588150
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01728818
- Acronym / sponsor ID
- ACCEPT / 2011-004063-77
- Conditions
- Focus of Study Instead
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 119 participants (actual)
- Lead sponsor
- PD Dr. med. Volker HeinemannUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim
- Study start
- Apr 2013
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2018 (estimated)
- First posted
- 20 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Gemcitabine, Drug: Afatinib |
| Arm B | Active comparator | Drug: Gemcitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Written informed consent in advance of any study-specific procedure
- Histologically (not cytologically) confirmed diagnosis of metastatic pancreatic adenocarcinoma (stage IV according to UICC 2009 classification: each T, each N, M1)
- Availability of tumour samples
- Informed consent that tumour- and blood samples are centrally collected and will serve for translational analyses according to the study protocol.
- Age >= 18 years
Key exclusion criteria (25 listed)
- Evidence of weight loss > 15% within one month
- Active brain metastases (stable for <28 days, symptomatic, or requiring concurrent steroids) or leptomeningeal disease. Patients who have received prior whole brain irradiation and whose brain metastases are stable according to the criteria above will not be excluded
- Previous gemcitabine treatment is allowed only if applied as monotherapy in the adjuvant setting and if the adjuvant single-agent gemcitabine chemotherapy was terminated at least 6 months before study entry
- Previous systemic treatment with chemotherapy or radiotherapy for locally advanced, non resectable or metastatic pancreatic cancer
- Radiotherapy within four weeks prior to randomization or radiation of target lesions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gemcitabine1000 mg/m² d1,8,15 q4weeks | Drug | Arm A |
| Afatinib40mg flat dose, po, once daily | Drug | Arm A |
| Gemcitabine1000 mg/m², d1,8,15 q4weeks | Drug | Arm B |
Primary outcome
Overall Survial
Time frame: approximately 36 months
Overall Survival
7 secondary outcomes
PFS
Time frame: Approximately 36 months
Duration of response
Time frame: approximately 36 months
1 Year Survial
Time frame: approximately 36 months
CA19-9
Time frame: approximately 36 months
Quality of life
Time frame: approximately 36 months
Toxicity
Time frame: approximately 36 months
Staging
Time frame: approximately 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2017.
- Derived from this study: PubMed 37794220Weiss L, Heinemann V, Fischer LE, Gieseler F, Hoehler T, Mayerle J, Quietzsch D, Reinacher-Schick A, Schenk M, Seipelt G, Siveke JT, Stahl M, Vehling-Kaiser U, Waldschmidt DT, Dorman K, Zhang D, Westphalen CB, von Bergwelt-Baildon M, Boeck S, Haas M. Three-month life expectancy as inclusion criterion for clinical trials in advanced pancreatic cancer: is it really a valid tool for patient selection? Clin Transl Oncol. 2024 May;26(5):1268-1272. doi: 10.1007/s12094-023-03323-1. Epub 2023 Oct 4.
- Derived from this study: PubMed 33588150Haas M, Waldschmidt DT, Stahl M, Reinacher-Schick A, Freiberg-Richter J, Fischer von Weikersthal L, Kaiser F, Kanzler S, Frickhofen N, Seufferlein T, Dechow T, Mahlberg R, Malfertheiner P, Illerhaus G, Kubicka S, Abdul-Ahad A, Snijder R, Kruger S, Westphalen CB, Held S, von Bergwelt-Baildon M, Boeck S, Heinemann V. Afatinib plus gemcitabine versus gemcitabine alone as first-line treatment of metastatic pancreatic cancer: The randomised, open-label phase II ACCEPT study of the Arbeitsgemeinschaft Internistische Onkologie with an integrated analysis of the 'burden of therapy' method. Eur J Cancer. 2021 Mar;146:95-106. doi: 10.1016/j.ejca.2020.12.029. Epub 2021 Feb 12.
- Homepage of the PancreasCenter at LMU MunichLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Volker Heinemann, Professor principal investigator
Medical Department III and Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gemcitabine and Afatinib in people with Focus of Study Instead, run by PD Dr. med. Volker Heinemann at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survial (time frame: approximately 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01728818, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2017.