NCT02620800

Study of 5-fluorouracil (5-FU), Nab®1-paclitaxel, Bevacizumab, Leucovorin, and Oxaliplatin in Patients With Metastatic Pancreatic Cancer

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.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Celgene · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Metastatic Pancreas Adenocarcinoma

Interventions

Type	Name	Description
DRUG	5FU	5 fluorouracil (5-FU) (180 mg/m\^2/day for 14 days) by CIVI via ambulatory pump
DRUG	nab-paclitaxel	nab-paclitaxel (75 mg/m\^2) as a 30-minute (min) IV infusion on Days 1, 8, and 15
DRUG	bevacizumab	bevacizumab (5 mg/kg) as an IV infusion on Days 1 and 15
DRUG	calcium leucovorin	calcium leucovorin (20 mg/m\^2) IV bolus, on Days 1, 8, 15
DRUG	oxaliplatin	oxaliplatin (40 mg/m\^2) as a 60-min IV infusion on Days 1, 8, and 15

Timeline

• Start date: 2016-01-18
• Primary completion: 2018-10-29
• Completion: 2018-10-29
• First posted: 2015-12-03
• Last updated: 2019-10-22

Locations

7 sites across 1 country: United States