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

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

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

Study Overview

• Status: Completed
• Conditions: Metastatic Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: nab-paclitaxel; Drug: gemcitabine; Drug: nab-paclitaxel; Drug: gemcitabine; Drug: m-FOLFOX

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28046
    • Spanish Cooperative for Digestive Tumour Therapy (TTD)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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; 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
Experimental: AG-mFOLFOX; nab-Paclitaxel followed by Gemcitabine and FOLFOXm at dose levels selected from the phase I trial	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; 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; Drug: m-FOLFOX; Day 28 according to the dose levels stablished in Phase I

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity for the AG-mFOLFOX combination	Primary outcome phase I.	12 weeks
Rate of overall survival al 12 months	Primary outcome phase II	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival		54 months
Rate of overall survival at 6 months		54 months
Rate of overall survival at 24 months		54 months
Time to tumor progression		54 months
Overall Survival		54 months
Objective radiographic response	Secondary outcome Phase I and Phase II	54 months
CA 19-9 biomarker response		54 months
Safety profile of this combination (AG-mFOLFOX) using NCI-CTCAE v.4 criteria	Secondary outcome Phase I and Phase II	54 months
To assess the Quality of Life of the patients through the EORTC QLQ-C30/PAN26 and EORTC QLQ-CIPN20 questionnaires	Secondary outcome Phase I and Phase II	54 months

Other Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Investigators: Study Chair: Alfredo Carrato, MD PhD, Hospital Universitario Ramon Y Cajal; Study Chair: Carmen Guillén, MD, Hospital Universitario Ramon Y Cajal

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: July 20, 2015
• First Submitted That Met QC Criteria: July 20, 2015
• First Posted (Estimated): July 21, 2015

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Gemcitabine; Nab-paclitaxel; metastatic pancreatic adenocarcinoma; modified FOLFOX
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine
• Other Study ID Numbers: TTD-14-05