Clinical trial NCT01303029: Safety and Efficacy Study of Gemcitabine-erlotinib Versus Gemcitabine-erlotinib-capecitabine in Patients With Metastatic Pancreatic Cancer
Official title: A Phase IIb Randomized Study to Evaluate the Efficacy of Gemcitabine-erlotinib Versus Gemcitabine-erlotinib-capecitabine in Patients With Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Pancreatic Cancer
Keywords: Pancreatic cancer
gemcitabine
erlotinib
capecitabine
Lead sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2011-02-24
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the efficacy of the combination of gemcitabine-erlotinib versus gemcitabine-erlotinib-capecitabine in patients with metastatic pancreatic cancer.


Eligibility criteria: Inclusion Criteria:

1. Ability to understand and willingness to sign a written informed consent
2. Able, in the investigator's opinion, to fulfill the procedures and explorations of the study
3. Age ≥ 18 years old
4. ECOG 0-2
5. Life expectancy ≥ 12 weeks
6. Patients with metastatic adenocarcinoma of the pancreas, following 7th edition of TNM classification
7. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas
8. Measurable disease following RECIST criteria version 1.1
9. No previous systemic treatment for metastatic pancreatic cancer Adjuvant chemotherapy al least 6 months before enrollment is allowed. Patients having neoadjuvant chemotherapy must have completed the treatment at least 4 weeks before trial entry. Toxicities associated to previous treatment must be resolved before enrollment. Progression disease (metastatic disease) must be confirmed after adjuvant treatment
10. Adequate bone marrow function as determined by:

    * Hemoglobin: ≥ 9 g/dL. (patients with hemoglobin \< 9 g/dL could be transfused before their inclusion on the study)
    * Platelets: ≥ 100 x 109/L
    * Absolute Neutrophil account (ANC) ≥ 1,5 x 109/L
11. Adequate liver function, as determined by:

    * Serum bilirubin ≤ 1,5 x LSN
    * AST, ALT ≤ 2,5 x LSN in patients without liver metastasis. In patients with liver metastasis ≤ 5 x LSN
    * Alkaline phosphatase ≤ 2,5 x LSN or ≤ 5 x LSN in patients with liver metastasis. In patients with bone metastasis ≤ 10 x LSN
12. Adequate renal function, as determined by:

    * Creatinine clearance using the Cockcroft-Gault formula ≥ 50.0 ml/min
13. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to randomization. Postmenopausal women are defined as those who have been amenorrheic for at least 12 months. Also, both men and women enrolled in this study must use adequate birth control (eg., abstinence, intrauterine device, oral contraceptive or double barrier method or be surgically sterile), starting at the signing of the informed consent and up to at least 6 months after completion of treatment or the last dose, whichever occurs first
14. Patients must not have undergone a major surgical procedure within 4 weeks prior to study treatment. The surgical wound should be completely healed

Exclusion Criteria:

1. Local pancreatic cancer (stage IA-IIB) or locally advance cancer (stage III), following the TNM 7th edition classification. Patients with metastatic disease that relapse after the initial diagnosis of local or advance disease could be included in this study
2. Pancreatic endocrine tumor and ampulloma
3. Evidence of carcinomatosis meningitis or brain metastasis. In case of clinical suspicious of brain metastasis is mandatory to perform a brain TAC/MR 4 weeks prior de inclusion.
4. Primary tumors developed 5 years previous to the inclusion, except in situ cervix carcinoma or skin basocellular cancer properly treated
5. Cardiovascular disease clinically significant (active):

   * Non-controlled arterial hypertension (Systolic pressure \> 150 mg Hg and/or diastolic pressure \> 100 mm Hg on repeated pressure measurements)
   * Cerebrovascular accident/ictus (≤ 6 weeks prior to inclusion)
   * Myocardial infarction (≤ 6 months prior to inclusion)
   * Unstable angina
   * Congestive cardiac insufficiency (grade II or superior following to New York Heart Association (NYHA)
   * Severe cardiac arrythmia requiring treatment
6. Significant ophthalmologic anomalies
7. Deficit in Dihydropyrimidine-Dehydrogenase (DPD)
8. Unable to take oral drug. Previous surgical process that affect the absorption or make the needed to have intravenous feeding or parenteral nutrition with lipids
9. Pregnancy women or in lactation period
10. Antineoplastic treatment (chemotherapy, hormonal treatment, radiotherapy, surgery, biological therapy or tumor embolization) 4 weeks prior the inclusion
11. Previous treatment with capecitabine or EGFR inhibitor
12. Metabolic disease or any other disease which, in the investigator's opinion, might interfere with the treatment in study
13. Known hypersensibility to any study drug (gemcitabine, erlotinib, capecitabine) or to 5-fluorouracile and fluoropyrimidines
14. Current infection grade ≥ 2 (CTCAE)
15. Known human immunodeficiency virus infection, or chronic infection with hepatitis B or C virus, or severe uncontrolled intercurrent infection or other severe uncontrolled concomitant diseases
16. Medical, psychological, psychiatric or sociological conditions that would interfere to the patient participation in the study or in the assessment of the results
17. Current or 30 days previous to study treatment with other investigational drug or participation in other trial

Primary outcomes:
measure: Progression free survival
timeFrame: 4 years
Secondary outcomes:
measure: Overall survival
timeFrame: 4 years
measure: Response rate (RR)
timeFrame: 4 years
measure: Duration of response
timeFrame: 4 years
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 4 years
measure: Percentage of rash in patients treated with erlotinib and progression free survival and overall survival and treatment relationship
timeFrame: 4 years
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Spanish Cooperative Group for Digestive Tumour Therapy
Study officials:
affiliation: Hospital de Toledo, Spain
name: Antonio Irigoyen, MD
role: STUDY_CHAIR
affiliation: Hospital Carlos Haya, Málaga. Spain
name: Manuel Benavides, MD
role: STUDY_CHAIR
References:
citation: Irigoyen A, Gallego J, Guillen Ponce C, Vera R, Iranzo V, Ales I, Arevalo S, Pisa A, Martin M, Salud A, Falco E, Saenz A, Manzano Mozo JL, Pulido G, Martinez Galan J, Pazo-Cid R, Rivera F, Garcia Garcia T, Serra O, Fernandez Parra EM, Hurtado A, Gomez Reina MJ, Lopez Gomez LJ, Martinez Ortega E, Benavides M, Aranda E; Spanish Cooperative Group of Treatment of Digestive Tumors (TTD). Gemcitabine-erlotinib versus gemcitabine-erlotinib-capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group. Eur J Cancer. 2017 Apr;75:73-82. doi: 10.1016/j.ejca.2016.12.032. Epub 2017 Mar 7.