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

• ClinicalTrials.gov Identifier: NCT02504333
• Recruitment Status: Completed
• First Posted: July 21, 2015
• Last Update Posted: October 3, 2023
• Sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Information provided by (Responsible Party): Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 168 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
• Actual Primary Completion Date: April 2021
• Actual Study Completion Date: April 2021

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 :

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/PAN26 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 ]

Eligibility Criteria

• 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/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.

Contacts and Locations

Locations

Spain

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

More Information

Additional Information:

Related Info 

• Responsible Party: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• ClinicalTrials.gov Identifier: NCT02504333
• Other Study ID Numbers: TTD-14-05
• First Posted: July 21, 2015
• Last Update Posted: October 3, 2023
• Last Verified: September 2023

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; Albumin-Bound Paclitaxel; Gemcitabine; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites