Afatinib as Cancer therapy for Exocrine Pancreatic Tumours
- Conditions
- histologically confirmed diagnosis of metastatic pancreatic adenocarcinomaMedDRA version: 19.0Level: LLTClassification code 10033575Term: Pancreas cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-004063-77-DE
- Lead Sponsor
- Klinikum der Universität München, Anstalt des öffentlichen Rechts
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 119
1. Written informed consent in advance of any study-specific procedure
2. Histologically (not cytologically) confirmed diagnosis of metastatic pancreatic adenocarcinoma (stage IV according to UICC 2009 classification: each T, each N, M1)
3. Availability of tumour samples
4. Informed consent that tumour- and blood samples are centrally collected and will serve for translational analyses according to the study protocol
5. Age = 18 years
6. ECOG 0-1
7. Life expectancy at least 3 months
8. No option for surgical resection or radiation in curative intent
9. At least one measurable tumour lesion (CT-scan or MRI) according to RECIST Version 1.1
10. Possibility of long-term follow-up
11. Negative pregnancy test in fertile females
12. Given legal capacity of the patient
13. Adequate hepatic, renal and bone marrow function, defined as:
- absolute neutrophil count > 1500/µl
- hemoglobin > 9 g/dl
- thrombocytes > 100 000/µl
- serum bilirubin < 2 x ULN (liver metastasis < 5 x ULN)
- serum creatinin < 1.5 x ULN
- creatinin clearance > 30 ml/min (Cockroft/Gault)
- transaminases < 2.5 x ULN (liver metastasis < 5 x ULN)
- albumin > 25 g/L
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Evidence of weight loss > 15 % within one month
2. 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
3. Previous gemcitabine treatment is allowed only if applied as monotherapy in the adjuvant setting (after potential curative R0 or R1 resection), and if the adjuvant single-agent gemcitabine chemotherapy was terminated at least 6 months before study entry
4. Previous systemic treatment with chemotherapy or radiotherapy for locally advanced, non resectable or metastatic pancreatic cancer
5. Radiotherapy within four weeks prior to randomization or radiation of target lesions
6. 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
7. Hypersensitivity to afatinib or to gemcitabine or to any of the excipients or to compounds with similar chemical or biologic composition
8. Contraindications against the use of gemcitabine
9. Severe renal insufficiency (baseline creatinine clearance < 30 ml/mi)
10. LDH elevated by >2.5 ULN
11. Severe hepatic dysfunction (bilirubin = 2.0 x ULN, transaminases = 2.5 x ULN or = 5 x ULN in case of liver metastases)
12. 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
13. 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
14. Pregnant or lactating females, non-effective contraception in men and women of childbearing potential (an effective contraceptive measure has a Pearl Index <1)
15. Any major surgery within the last 2 weeks before study entry
16. Chemo- or immunotherapy within the past 4 weeks
17. 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
18. Any persisting toxicities which are deemed to be clinically significant from the previous therapy
19. Patients with pre-existing interstitital lung disease
20. Psychological, familial, social or geographic conditions that may prevent an adequate compliance with the study protocol
21. Known or suspected alcohol- or drug abuse
22. Patients unable to comply with the protocol
23. Known hepatitis B infection, known hepatitis C infection or HIV carrier
24. Requirement for treatment with any of the prohibited concomitant medications listed in section 4.3.2
25. 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: - to demonstrate that the combination of afatinib plus gemcitabine is superior to gemcitabine alone in the treatment of metastatic pancreatic cancer;Secondary Objective: - accompanying translational research program: to define parameters which may serve to provide prognostic information or predict treatment efficacy;Primary end point(s): Overall survival;Timepoint(s) of evaluation of this end point: - During study treatment: weekly/biweekly assessment<br>- during Follow Up: every 3 months for a total duration of 12 months after end of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Progression free survival<br>- Duration of response<br>- 1-year survival<br>- Biochemical tumour marker response (serum CA 19-9)<br>- Quality of life (EORTC QLQ C-30)<br>- Toxicity (NCI CTC-AE v4.0)<br>- explorative endpoint of translational research program: focus on potential prognostic and predictive biomarkers associated with the EGFR pathway (e.g. EGFR, HER2-HER4, PTEN, KRAS, EGFR intron 1 polymorphism, epiregulin, amphiregulin, single nucleotide polymorphism) and gemcitabin metabolism/toxicity (e.g. hENT1, RRM1, CDA);Timepoint(s) of evaluation of this end point: During study treatment:<br>- response will be assessed every two cycles (8 weeks)<br>- CA 19-9 and Quality of life: every cycle<br>- toxicity: weekly/biweekly<br>During Follow Up:<br>- toxicity and survival will be assessed every 3 months for a total period of 12 months after end of treatment<br>- translational program: tumour and blood samples will be collected once during screening