Metastatic Pancreas Adenocarcinoma Clinical Trial
Official title:
An Open Label, Multicenter, Single Arm, Phase 1/2 Trial of Metronomic 5-fluorouracil in Combination With Nab-paclitaxel, Bevacizumab, Leucovorin, and Oxaliplatin in Patients With Metastatic Pancreatic Adenocarcinoma.
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.
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.
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