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

Phase 1

Completed

• Conditions: Metastatic Pancreatic Adenocarcinoma
• Interventions: Drug: nab-paclitaxel; Drug: m-FOLFOX; Drug: gemcitabine

• Registration Number: NCT02504333
• Lead Sponsor: 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

Detailed Description

Not available

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2015-07-20
• Study First Submitted QC: 2015-07-20
• Study First Posted: 2015-07-21
• Primary Completion: 2021-04
• Study Completion: 2021-04
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-29
• Last Update Posted: 2023-10-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 168

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AG	nab-paclitaxel	nab-Paclitaxel followed by Gemcitabine
AG	gemcitabine	nab-Paclitaxel followed by Gemcitabine
AG-mFOLFOX	m-FOLFOX	nab-Paclitaxel followed by Gemcitabine and FOLFOXm at dose levels selected from the phase I trial
AG-mFOLFOX	nab-paclitaxel	nab-Paclitaxel followed by Gemcitabine and FOLFOXm at dose levels selected from the phase I trial
AG-mFOLFOX	gemcitabine	nab-Paclitaxel followed by Gemcitabine and FOLFOXm at dose levels selected from the phase I trial

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Rate of overall survival at 6 months	54 months
CA 19-9 biomarker response	54 months
Time to tumor progression	54 months
Progression free survival	54 months
Objective radiographic response	54 months	Secondary outcome Phase I and Phase II
Rate of overall survival at 24 months	54 months
Overall Survival	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/PAN26 and EORTC QLQ-CIPN20 questionnaires	54 months	Secondary outcome Phase I and Phase II

Trial Locations

Locations (1)

Spanish Cooperative for Digestive Tumour Therapy (TTD); 🇪🇸 Madrid, Spain