A phase II Biomarker Identification Trial for Erlotinib (Tarceva®) in Patients with Advanced Pancreatic Carcinoma - MARK

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2007-003738-40-SI
• Date of registration: 01/09/2008
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche
• Public title: A phase II Biomarker Identification Trial for Erlotinib (Tarceva®) in Patients with Advanced Pancreatic Carcinoma - MARK
• Scientific title: A phase II Biomarker Identification Trial for Erlotinib (Tarceva®) in Patients with Advanced Pancreatic Carcinoma - MARK
• Date of first enrolment: 15/10/2008
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003738-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Bulgaria, Germany, Italy, Latvia, Lithuania, Slovenia, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically or cytologically confirmed locally advanced-unresectable or metastatic pancreatic cancer
2. Measurable disease according to RECIST (irradiated lesions can not be used as target lesions)
3. Failure of at least one prior chemotherapy regimen or patients who are deemed unsuitable for chemotherapy in the investigators opinion. >= 4 weeks since last chemotherapy or treatment with another systemic anti-cancer agent. Patients must have recovered (CTC <= 1) from acute toxicities of any previous therapy (with the exception of alopecia).
4. Patients may have received prior radiotherapy for management of local disease providing that disease progression has been documented, all toxicities have resolved (CTC <= 1) (with the exception of alopecia), and the last fraction of radiotherapy was completed at least 4 weeks prior to randomization.
5. Life expectancy of = 6 week
6. Age >= 18 years
7. ECOG performance status of 0 - 1 (see section 5.3.2)
8. Able to comply with the protocol
9. Written (signed) Informed Consent to participate in the study
10. Patient must be willing and able to undergo biopsy according to the institute’s own guidelines and requirements for such procedures.
11. Adequate hematological function: ANC >= 1.5 x 109/L, platelet count >= 100 x 109/L and Hb >= 9 g/dL
12. INR <= 1.5 and PTT <=1.5 x ULN within 7 days prior to randomization
13. Platelet aggregation inhibitors must discontinued within an appropriate time period before biopsy
14. Adequate liver function: Serum (total) bilirubin <= 1.5 x ULN, SGOT (AST) and SGPT (ALT) < 2.5 x ULN in the absence of liver metastases or up to 5 x ULN in case of liver metastases,
15. Albumin >= 2.5 g/dL
16. Adequate renal function: serum creatinine < 1.5 ULN
17. Normal serum calcium
18. For all females of childbearing potential a negative pregnancy test must be obtained within 7 days before start of treatment.

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

Exclusion criteria:
1. Local (Stage IA to IIB) pancreatic cancer and locally advanced-resectable pancreatic cancer.
2. Prior treatment with an investigational or marketed agent which acts on the EGFR axis. EGFR inhibitors include (but are not limited to) erlotinib, gefitinib or other anti-EGFR or EGF monoclonal antibody therapy or dual TKI inhibitors
3. 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
4. Evidence of spinal cord compression or current evidence of CNS metastases. CT/MRI of the brain is mandatory (within 4 weeks before study start) in case of clinical suspicion or evidence of brain metastases
5. Any disease (including psychotic disorders, drug abuse, 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, hepatic, renal or metabolic disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications
6. Patients who have had any major surgery within 2 weeks prior to study start
7. Any known significant ophthalmologic abnormalities of the surface of the eye (the use of contact lenses is not recommended)
8. Patients unable to take oral medication, requiring intravenous alimentation, who have mal-absorption syndrome or any other conditions affecting gastrointestinal absorption, or who have active peptic ulcer disease
9. Pregnant or lactating females
10. Men and women of childbearing potential (<2 years after last menstruation) not using effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile)
11. Current or recent (within the 30 days prior to starting study treatment) treatment with another investigational drug or participation in another investigational study
12. Patients known to be HIV positive. Testing is not required in the absence of clinical signs and symptoms suggestive of HIV infection.
13. Patients using coumadin or warfarin
14. Known hypersensitivity to any of the study drugs or their excipients.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pancreatic cancer
MedDRA version: 9.1 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic
MedDRA version: 9.1 Level: LLT Classification code 10033606 Term: Pancreatic cancer non-resectable

Intervention(s)

Trade Name: Tarceva
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Erlotinib
CAS Number: 183321-74-6
Current Sponsor code: Ro 50-8231
Other descriptive name: erlotinib hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Tarceva
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Erlotinib
CAS Number: 183321-74-6
Current Sponsor code: Ro 50-8231
Other descriptive name: erlotinib hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Tarceva
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Erlotinib
CAS Number: 183321-74-6
Current Sponsor code: Ro 50-8231
Other descriptive name: erlotinib hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Secondary Objective: Assessment of efficacy and safety

Main Objective: Identification of biomarker(s) which may predict improvement in progression free survival from treatment with erlotinib

Primary end point(s): - Assessment of EGFR expression and gene copy number in tumor tissue
- Assessment of HER2 and HER3 expression in tumor tissue
- Assessment k-RAS mutation status in tumor tissue
- Assessment of EGFR ligands in serum and tissue
- EGFR Intron 1 polymorphism in blood

Secondary ID(s)

2007-003738-40-IT

BO21129