Clinical trial NCT02504333: Phase I/II Study of Nab-paclitaxel and Gemcitabine Followed by AG-mFOLFOX in Patients With Metastatic Pancreatic Adenocarcinoma
Official title: A Phase I/II Study of Nab-paclitaxel (Abraxane) and Gemcitabine Followed by Modified FOLFOX (AG-mFOLFOX) in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Pancreatic Adenocarcinoma
Keywords: metastatic pancreatic adenocarcinoma
Nab-paclitaxel
Gemcitabine
modified FOLFOX
Lead sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Sponsor class: OTHER
First posted: 2015-07-21
Enrollment: 168
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 this study is to assess the safety and efficacy of nab-paclitaxel (Abraxane) and gemcitabine followed by modified FOLFOX (AG-mFOLFOX) in patients with previously untreated, metastatic pancreatic adenocarcinoma


Eligibility criteria: Inclusion Criteria:

1. Histologically and/or cytologically confirmed pancreatic adenocarcinoma
2. Stage IV disease (metastatic only)
3. No prior systemic therapy for their diagnosis (except in adjuvant/neoadjuvant setting\>six months previously)
4. ECOG performance status of 0-1
5. At least 18 years of age
6. Evidence of either or both of the following RECIST-defined measurable disease (lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20mm using conventional techniques or ≥10 mm with spiral CT scan)
7. Female patients must be either surgically sterile or postmenopausal, or if of childbearing potential must have a negative pregnancy test (serum or urine) prior to enrollment and agree to use effective barrier contraception during the period of therapy. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the investigator.
8. Adequate bone marrow function:

   * ANC ≥ 1500/uL
   * platelet count ≥ 100,000/uL
   * hemoglobin ≥ 9.0 g/dL
9. Adequate hepatic function:

   * Total bilirubin ≤ 1.5 X ULN
   * AST (SGOT) ≤ 2.5 X ULN
   * ALT (SGPT) ≤ 2.5 X ULN
10. Adequate renal function as determined by either:

    - Calculated or measured creatinine clearance ≥ 40 mL/min (for calculated creatinine clearance, Cockroft-Gault equation will be used).
11. Ability to understand the nature of this study protocol and give written informed consent.
12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

1. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that, in the opinion of the investigator, renders the subject at high risk from treatment complications or might affect the interpretation of the results of the study.
2. Presence of central nervous system or brain metastases.
3. Life expectancy \< 12 weeks
4. Pregnancy (positive pregnancy test) or lactation.
5. Pre-existing sensory neuropathy \> grade 1.
6. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months.
7. Major surgery and/or radiotherapy within 4 weeks of the start of study treatment, without complete recovery.
8. Prior malignancy except for adequately treated basal cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other form of cancer from which the patient has been disease-free for 5 years.

Primary outcomes:
measure: Dose-limiting toxicity for the AG-mFOLFOX combination
timeFrame: 12 weeks
measure: Rate of overall survival al 12 months
timeFrame: 12 weeks
Secondary outcomes:
measure: Rate of overall survival at 6 months
timeFrame: 54 months
measure: Rate of overall survival at 24 months
timeFrame: 54 months
measure: Time to tumor progression
timeFrame: 54 months
measure: Progression free survival
timeFrame: 54 months
measure: Overall Survival
timeFrame: 54 months
measure: Objective radiographic response
timeFrame: 54 months
measure: CA 19-9 biomarker response
timeFrame: 54 months
measure: Safety profile of this combination (AG-mFOLFOX) using NCI-CTCAE v.4 criteria
timeFrame: 54 months
measure: To assess the Quality of Life of the patients through the EORTC QLQ-C30/PAN26 and EORTC QLQ-CIPN20 questionnaires
timeFrame: 54 months
Other outcomes:
measure: microRNA expression levels and their correlation with tumour-efficacy parameters
timeFrame: 54 months
measure: Biomarker determination (tissue sample at basal point and blood samples at basal and at the end of treatment). Correlation with treatment response
timeFrame: 54 months
Locations:
city: Madrid
country: Spain
facility: Spanish Cooperative for Digestive Tumour Therapy (TTD)
Study officials:
affiliation: Hospital Universitario Ramón y Cajal
name: Alfredo Carrato, MD PhD
role: STUDY_CHAIR
affiliation: Hospital Universitario Ramón y Cajal
name: Carmen Guillén, MD
role: STUDY_CHAIR
References: