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

Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Metastatic Pancreatic Adenocarcinoma

Treatments: Drug: gemcitabine; Drug: m-FOLFOX; Drug: nab-paclitaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT02504333

TTD-14-05

Details and patient eligibility

About

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

Enrollment: 168 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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168 participants in 2 patient groups

AG

Active Comparator group

Description:

nab-Paclitaxel followed by Gemcitabine

Treatment:

Drug: nab-paclitaxel

Drug: gemcitabine

Drug: gemcitabine

Drug: nab-paclitaxel

AG-mFOLFOX

Experimental group

Description:

nab-Paclitaxel followed by Gemcitabine and FOLFOXm at dose levels selected from the phase I trial

Treatment:

Drug: nab-paclitaxel

Drug: m-FOLFOX

Drug: gemcitabine

Drug: gemcitabine

Drug: nab-paclitaxel