Study of 5-fluorouracil (5-FU), Nab®1-paclitaxel, Bevacizumab, Leucovorin, and Oxaliplatin in Patients With Metastatic Pancreatic Cancer
Condition: Metastatic Pancreas Adenocarcinoma
MeSH terms: Adenocarcinoma
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to learn about the safety and potential benefit of metronomic
      5-fluorouracil in combination with nab®1-paclitaxel, bevacizumab, leucovorin, and oxaliplatin
      in treating patients with metastatic pancreatic adenocarcinoma.
    

Detailed description: 
      The Phase 1 portion of the study is an open-label study enrolling subjects with metastatic
      pancreatic adenocarcinoma who have not previously received systemic chemotherapy at any time
      as treatment for pancreatic cancer (including adjuvant chemotherapy), except low dose
      chemotherapy administered as a radiosensitizer concomitant with radiotherapy and to determine
      the recommended Phase 2 dose (RP2D) and dose-limiting toxicities (DLTs) of metronomic 5-FU in
      combination with nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin in patients with
      metastatic pancreatic adenocarcinoma.

      Subjects will be enrolled in cohorts of 6 subjects. There will be no dose escalation. Dose
      limiting toxicities will be assessed in cycle 1. If there is an incidence of ≥2 of 6 subjects
      experiencing a DLT, the dose will be de-escalated to the next lower dose. Based on the
      totality of the data, the investigators may advise the Sponsor to evaluate additional
      subjects at any of the dose levels. Upon Sponsor agreement, if additional subjects are
      enrolled at any dose level, DLT evaluation will occur at that same ratio (if ≥ 4 of 12
      subjects, or ≥ 6 of 18 subjects experience a DLT, the dose will be de-escalated).
      Approximately 12-24 subjects will be enrolled in the Phase 1 portion of the study, dependent
      on the number of dose levels examined and the number of subjects enrolled at each dose level.

      Safety will continuously be evaluated by incidence of Treatment Emergent Adverse Events
      (TEAEs) by the Medical Dictionary for Drug Regulatory Activities (MedDRA) and severity
      according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI
      CTCAE) Version 4.03 (v4.03).

      The Phase 2 part of the study is to determine if the combination of metronomic 5-FU,
      nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin at the RP2D defined in Phase 1
      achieves a clinically meaningful improvement in 1 year survival rate over the historical
      control. Approximately 60 subjects are planned to be enrolled in the Phase 2 portion of the
      study.

      Subjects may remain on treatment until disease progression, unacceptable toxicity, withdrawal
      of consent, physician decision, or death. The anticipated duration of the study (including
      Phase 1, Phase 2 and follow-up) is approximately 4 years.

      The Phase 1 portion of the study is an open-label study enrolling subjects with metastatic
      pancreatic adenocarcinoma who have not previously received systemic chemotherapy at any time
      as treatment for pancreatic cancer (including adjuvant chemotherapy), except low dose
      chemotherapy administered as a radiosensitizer concomitant with radiotherapy and to determine
      the recommended Phase 2 dose (RP2D) and dose-limiting toxicities (DLTs) of metronomic 5-FU in
      combination with nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin in patients with
      metastatic pancreatic adenocarcinoma.

      Subjects will be enrolled in cohorts of 6 subjects. There will be no dose escalation. Dose
      limiting toxicities will be assessed in cycle 1. If there is an incidence of ≥2 of 6 subjects
      experiencing a DLT, the dose will be de-escalated to the next lower dose. Based on the
      totality of the data, the investigators may advise the Sponsor to evaluate additional
      subjects at any of the dose levels. Upon Sponsor agreement, if additional subjects are
      enrolled at any dose level, DLT evaluation will occur at that same ratio (if ≥ 4 of 12
      subjects, or ≥ 6 of 18 subjects experience a DLT, the dose will be de-escalated).
      Approximately 12-24 subjects will be enrolled in the Phase 1 portion of the study, dependent
      on the number of dose levels examined and the number of subjects enrolled at each dose level.

      Safety will continuously be evaluated by incidence of Treatment Emergent Adverse Events
      (TEAEs) by the Medical Dictionary for Drug Regulatory Activities (MedDRA) and severity
      according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI
      CTCAE) Version 4.03 (v4.03).

      The Phase 2 part of the study is to determine if the combination of metronomic 5-FU,
      nab-paclitaxel, bevacizumab, leucovorin, and oxaliplatin at the RP2D defined in Phase 1
      achieves a clinically meaningful improvement in 1 year survival rate over the historical
      control. Approximately 60 subjects are planned to be enrolled in the Phase 2 portion of the
      study.

      Subjects may remain on treatment until disease progression, unacceptable toxicity, withdrawal
      of consent, physician decision, or death. The anticipated duration of the study (including
      Phase 1, Phase 2 and follow-up) is approximately 4 years.

      Upon completion of the Phase 1 portion of the study, a decision not to proceed with the Phase
      2 portion was taken by the Sponsor. The decision to terminate the study after Phase 1 was not
      based on any safety concerns that posed an unacceptable risk for this patient population and
      no safety issues have been identified.
    

Intervention name(s): 5FU; nab-paclitaxel; bevacizumab; calcium leucovorin; oxaliplatin
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 5 fluorouracil (5-FU) (180 mg/m^2/day for 14 days) by CIVI via ambulatory pump; nab-paclitaxel (75 mg/m^2) as a 30-minute (min) IV infusion on Days 1, 8, and 15; bevacizumab (5 mg/kg) as an IV infusion on Days 1 and 15; calcium leucovorin (20 mg/m^2) IV bolus, on Days 1, 8, 15; oxaliplatin (40 mg/m^2) as a 60-min IV infusion on Days 1, 8, and 15
Other intervention name(s): Abraxane; ABI-007; Avastin; Citrovorum Factor; Folinic Acid; Elotaxin
Intervention MeSH terms: Leucovorin; Paclitaxel; Bevacizumab; Oxaliplatin; Calcium; Levoleucovorin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Metastatic Pancreatic Cancer; Adenocarcinoma; Open-label; Phase 1/2; Metronomic; Chemotherapy; ABI-007; nab-paclitaxel; Abraxane; gemcitabine; Gemzar; bevacizumab; Avastin; 5-Fluorouracil (5-FU); leucovorin; oxaliplatin; Eloxatin