SEQUENCE: Phase I/II Study of Nab-paclitaxel and Gemcitabine Followed by AG-mFOLFOX in Patients With Metastatic Pancreatic Adenocarcinoma
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: AG nab-Paclitaxel followed by Gemcitabine |
Drug: nab-paclitaxel
Day 1-8-15: Intravenous, 125 mg/m2 over 30 minutes
Drug: gemcitabine
Day 1-8-15: Intravenous, 1.000 mg/m2 over 30 minutes
|
| Experimental: AG-mFOLFOX nab-Paclitaxel followed by Gemcitabine and FOLFOXm at dose levels selected from the phase I trial |
Drug: m-FOLFOX
Day 28 according to the dose levels stablished in Phase I
Drug: nab-paclitaxel
Day 1-8-15: Intravenous 30 minutes according to the dose levels stablished in Phase I
Drug: gemcitabine
Day 1-8-15: Intravenous 30 minutes according to the dose levels stablished in Phase I
|
Outcome Measures
Primary Outcome Measures
- Dose-limiting toxicity for the AG-mFOLFOX combination [12 weeks]
Primary outcome phase I.
- Rate of overall survival al 12 months [12 weeks]
Primary outcome phase II
Secondary Outcome Measures
- Rate of overall survival at 6 months [54 months]
- Rate of overall survival at 24 months [54 months]
- Time to tumor progression [54 months]
- Progression free survival [54 months]
- Overall Survival [54 months]
- Objective radiographic response [54 months]
Secondary outcome Phase I and Phase II
- CA 19-9 biomarker response [54 months]
- Safety profile of this combination (AG-mFOLFOX) using NCI-CTCAE v.4 criteria [54 months]
Secondary outcome Phase I and Phase II
- To assess the Quality of Life of the patients through the EORTC QLQ-C30 and EORTC QLQ-CIPN20 questionnaires [54 months]
Secondary outcome Phase I and Phase II
Other Outcome Measures
- microRNA expression levels and their correlation with tumour-efficacy parameters [54 months]
- Biomarker determination (tissue sample at basal point and blood samples at basal and at the end of treatment). Correlation with treatment response [54 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically and/or cytologically confirmed pancreatic adenocarcinoma
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Stage IV disease (metastatic only)
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No prior systemic therapy for their diagnosis (except in adjuvant setting>six months previously)
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ECOG performance status of 0-1
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At least 18 years of age
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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)
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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.
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Adequate bone marrow function:
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ANC ≥ 1500/uL
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platelet count ≥ 100,000/uL
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hemoglobin ≥ 9.0 g/dL
- Adequate hepatic function:
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Total bilirubin ≤ 1.5 X ULN or until 2mg/dL
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AST (SGOT) ≤ 2.5 X ULN
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ALT (SGPT) ≤ 2.5 X ULN
- 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).
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Ability to understand the nature of this study protocol and give written informed consent.
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Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Exclusion Criteria:
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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.
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Presence of central nervous system or brain metastases.
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Life expectancy < 12 weeks
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Pregnancy (positive pregnancy test) or lactation.
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Pre-existing sensory neuropathy > grade 1.
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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.
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Major surgery within 4 weeks of the start of study treatment, without complete recovery.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Spanish Cooperative for Digestive Tumour Therapy (TTD) | Madrid | Spain | 28046 |
Sponsors and Collaborators
- Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Investigators
- Study Chair: Alfredo Carrato, MD PhD, Hospital Universitario Ramón y Cajal
- Study Chair: Carmen Guillén, MD, Hospital Universitario Ramón y Cajal
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- TTD-14-05