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Phase I/II Study of Nab-paclitaxel and Gemcitabine Followed by AG-mFOLFOX in Patients With Metastatic Pancreatic Adenocarcinoma (SEQUENCE)

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ClinicalTrials.gov Identifier: NCT02504333
Recruitment Status : Recruiting
First Posted : July 21, 2015
Last Update Posted : August 2, 2018
Sponsor:
Information provided by (Responsible Party):
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

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
Metastatic Pancreatic Adenocarcinoma Drug: nab-paclitaxel Drug: gemcitabine Drug: m-FOLFOX Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : July 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Dose-limiting toxicity for the AG-mFOLFOX combination [ Time Frame: 12 weeks ]
    Primary outcome phase I.

  2. Rate of overall survival al 12 months [ Time Frame: 12 weeks ]
    Primary outcome phase II


Secondary Outcome Measures :
  1. Rate of overall survival at 6 months [ Time Frame: 54 months ]
  2. Rate of overall survival at 24 months [ Time Frame: 54 months ]
  3. Time to tumor progression [ Time Frame: 54 months ]
  4. Progression free survival [ Time Frame: 54 months ]
  5. Overall Survival [ Time Frame: 54 months ]
  6. Objective radiographic response [ Time Frame: 54 months ]
    Secondary outcome Phase I and Phase II

  7. CA 19-9 biomarker response [ Time Frame: 54 months ]
  8. Safety profile of this combination (AG-mFOLFOX) using NCI-CTCAE v.4 criteria [ Time Frame: 54 months ]
    Secondary outcome Phase I and Phase II

  9. To assess the Quality of Life of the patients through the EORTC QLQ-C30 and EORTC QLQ-CIPN20 questionnaires [ Time Frame: 54 months ]
    Secondary outcome Phase I and Phase II


Other Outcome Measures:
  1. microRNA expression levels and their correlation with tumour-efficacy parameters [ Time Frame: 54 months ]
  2. Biomarker determination (tissue sample at basal point and blood samples at basal and at the end of treatment). Correlation with treatment response [ Time Frame: 54 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 or until 2mg/dL
    • 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02504333


Contacts
Contact: Inmaculada Ruiz de Mena, PhD +34 91 378 82 75 ttd@ttdgroup.org

Locations
Spain
Spanish Cooperative for Digestive Tumour Therapy (TTD) Recruiting
Madrid, Spain, 28046
Contact: Inmaculaa Ruiz de Mena, PhD    +34 91 378 82 75    ttd@ttdgroup.org   
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

Additional Information:
Responsible Party: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
ClinicalTrials.gov Identifier: NCT02504333     History of Changes
Other Study ID Numbers: TTD-14-05
First Posted: July 21, 2015    Key Record Dates
Last Update Posted: August 2, 2018
Last Verified: August 2018

Keywords provided by Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD):
metastatic pancreatic adenocarcinoma
Nab-paclitaxel
Gemcitabine
modified FOLFOX

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Paclitaxel
Gemcitabine
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs