A Phase II, Dose-Escalation to rash Trial of Erlotinib (Tarceva®) plus Gemcitabine in Patients With Metastatic Pancreatic Cancer. - RACHEL

• Register: EUCTR
• Last refreshed on: 10 February 2014
• Main ID: EUCTR2007-003751-37-DE
• Date of registration: 19/03/2008
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: A Phase II, Dose-Escalation to rash Trial of Erlotinib (Tarceva®) plus Gemcitabine in Patients With Metastatic Pancreatic Cancer. - RACHEL
• Scientific title: A Phase II, Dose-Escalation to rash Trial of Erlotinib (Tarceva®) plus Gemcitabine in Patients With Metastatic Pancreatic Cancer. - RACHEL
• Date of first enrolment: 09/07/2008
• Target sample size: 560
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003751-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Different dose

Countries of recruitment

Austria, Belgium, France, Germany, Greece, Italy, Lithuania, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
NB: These are inclusion criteria for initial 4 weeks run-in period. Disease specific inclusion criteria:
1. Histologically or cytologically confirmed pancreatic cancer (adenocarcinoma) with measurable or non-measurable metastatic disease (stage IV)
2. Life expectancy of =8 weeks
General inclusion criteria:
3. Age =18 years
4. ECOG performance status of 0 - 1 (see section 5.3.2 of the protocol)
5. Able to comply with the protocol
6. Written (signed) Informed Consent to participate in the study
7. Adequate hematological function: ANC =1.5 x 109/L, platelet count =100 x 109/L and Hb =9 g/dL
8. PT-INR =1.5 and PTT =1.5 x ULN within 7 days prior to start of study treatment
9. Adequate liver function: serum (total) bilirubin =1.5 x ULN, SGOT (AST) and SGPT (ALT) < 2.0 x ULN
10. Albumin > 3.0 g/dL
11. Adequate renal function: serum creatinine < 1.5 ULN
12. For all females of childbearing potential a negative pregnancy test must be obtained within 7 days before start of treatment.

Inclusion criteria for randomization between day 29 and 35 (after 4 weeks run-in period)
1. Completion of 4 weeks run-in period, without clinical evidence of disease progression, as per investigators opinion
2. Patients who have not developed rash grade =2 during the 4 weeks run-in period
3. Patients who have not developed any other toxicity leading to dose adjustments /
discontinuation (for either gemcitabine or erlotinib) during the 4 weeks run-in period. Patients who during the run-in period have had only one gemcitabine related dose reduction (75% of full dose) for hematological toxicity, are eligible for randomization provided they are stable and tolerating the 75% of full dose and no further reductions are anticipated
4. ECOG performance status of 0 - 1 (see section 5.3.2)
5. Adequate hematological function: ANC =1.5 x 109/L, platelet count =100 x 109/L
and Hb =9 g/dL
6. Adequate liver function: serum (total) bilirubin =1.5 x ULN, SGOT (AST) and
SGPT (ALT) < 2.0 x ULN
7. Albumin > 3.0 g/dL
8. Adequate renal function: serum creatinine < 1.5 ULN

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:
Exclusion Criteria for initial 4 weeks run-in period Disease specific exclusion criteria: 1. Local (Stage Ia to IIb) pancreatic cancer and locally advanced (stage III) pancreatic cancer. (Patients relapsing with metastatic disease, after initial diagnosis with local or locally advanced disease can be enrolled into this study)
2. Prior chemotherapy or treatment with another systemic anti-cancer agent for locally advanced-unresectable or metastatic pancreatic cancer
3. Less than (or equal to) 6 months since last adjuvant chemotherapy. Patient must have recovered from all treatment related toxicities prior to 4 weeks run-in period and must have documented evidence of disease progression (metastatic) following adjuvant chemotherapy
4. 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
5. Prior adjuvant radiotherapy for pancreatic cancer, except for patients with progressive lesions outside the radiation port who completed the radiotherapy at least 6 months prior to study entry
6. 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
7. 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
General exclusion criteria:
8. 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
9. Patients who have had any major surgery within 2 weeks prior to study start
10. Any known significant ophthalmologic abnormalities of the surface of the eye (the use of contact lenses is not recommended)
11. 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
12. Pregnant or lactating females
13. Men and women of childbearing potential (<2 years after last menstruation) not using effective means of contraception (e.g. oral contraceptives, intrauterine contraceptive device, sexual abstinence, or surgically sterile), effective meaning failure rate < 1%/year
14. Current or recent (within the 30 days prior to starting study treatment) treatment with another investigational drug or participation in another investigational study
15. Patients known to be HIV positive. Testing is not required in the absence of clinical signs and symptoms suggestive of HIV infection.
16. Hypersensitivity to erlotinib or to gemcitabine or to any of the excipients or to compounds with similar chemical or biologic composition



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

Health Condition(s) or Problem(s) studied

Pancreatic cancer
MedDRA version: 12.0 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic

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-

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: • To evaluate the safety and tolerability of increased doses of erlotinib in combination with gemcitabine.
• To evaluate if increasing the dose of erlotinib increases the incidence of grade >= 2 rash vs. those who continue on 100 mg erlotinib
• To compare PFS, response and disease control rates between patients with increased dose of erlotinib vs. those who continue on 100 mg erlotinib.
• To make a non randomized comparison of efficacy and safety between patients who do develop vs. those who do not develop grade 2 or higher rash during the first 4 weeks of therapy.
• To correlate biomarkers (EGFR expression, EGFR gene copy number, K-ras mutations, EGFR Intron 1 polymorphisms) with outcomes and response to treatment (ORR, PFS, OS).

Primary end point(s): Primary efficacy parameter is Overall Survival (OS).

Main Objective: To determine, in patients who do not develop any rash, or develop only grade 1 rash, within 4 weeks of start of treatment with gemcitabine + erlotinib, if overall survival can be improved by increasing the dose of erlotinib compared to patients who continue on 100 mg erlotinib.

Secondary ID(s)

2007-003751-37-FR

BO21128