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

NCT02620800 | Completed Phase 1 DMC

• 1 other identifier: ABI-007-PANC-009
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Metastatic Pancreas Adenocarcinoma

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

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicities (Phase 1)

  • Any toxicity starting during the first 28 days of treatment and requiring 14 days or more of treatment interruption • Grade 3 or 4 neutropenia associated with fever \> 38.5°C • Grade 3 anemia requiring a transfusion • Any Grade 4 hematological toxicity lasting \> 7 days • Grade 4 thrombocytopenia or a Grade 3 or 4 thrombocytopenia associated with clinically significant bleeding • Grade 3 or 4 non-hematological toxicity with the exception of fatigue, due to any of the study drugs and unresponsive to medical treatment within 4 days of onset • Subjects who experience Grade ≥ 3 hyperbilirubinemia as an apparent DLT. If a Phase 1 subject experiences a Grade ≥ 3 hyperbilirubinemia due principally to unconjugated bilirubin, it will not be defined as a DLT. The subject will be removed from the study and the Phase 1 subject will be replaced. • Any non-hematologic toxicity delaying the initiation of cycle 2 by \> 21 days • Grade ≥ 2 pneumonitis or interstitial lung disease

  Up to Day 1 of Cycle 2

• 1 year survival rate (Phase II portion)

  1 year survival rate is defined as the time interval between the date of first dose of Investigational Product (IP) and the date of death.

  Up to 1 year

• Number of subjects experiencing Adverse Events (AEs) by severity and overall tabulations by cohort and overall including treatment emergent and Serious AEs

  An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. All AEs will be recorded by the Investigator from the time the subject signs informed consent until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to Investigational Product.

  Up to 4 years

Secondary Outcomes (7)

• Summary for the number of subjects experiencing Adverse Events (AEs) by severity and overall in tabulations by cohort and overall including treatment emergent AEs and Serious AEs

  Up to 4 years

• Objective Response Rate using Response Evaluation Criteria In Solid Tumours (Recist) v1.1 presented by frequency and percentages

  Up to 4 years

• Progression free survival (PFS)

  Up to 4 years

• Overall Survival (OS)

  Up to 4 years

• Percentage of subjects with symptom improvement

  Up to 4 years

Study Arms (1)

FABLOx

EXPERIMENTAL

5 fluorouracil (5-FU ) (180 mg/m\^2/day for 14 days), by continuous intravenous infusion (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, and oxaliplatin (40 mg/m\^2) as a 60-min IV infusion on Days 1, 8, and 15. First bevacizumab infusion is given over 90 minutes.

Drug: 5FU; Drug: nab-paclitaxel; Drug: bevacizumab; Drug: calcium leucovorin; Drug: oxaliplatin

Interventions

5FU DRUG

5 fluorouracil (5-FU) (180 mg/m\^2/day for 14 days) by CIVI via ambulatory pump

FABLOx

nab-paclitaxel DRUG

nab-paclitaxel (75 mg/m\^2) as a 30-minute (min) IV infusion on Days 1, 8, and 15

Also known as: Abraxane, ABI-007

FABLOx

bevacizumab DRUG

bevacizumab (5 mg/kg) as an IV infusion on Days 1 and 15

Also known as: Avastin

FABLOx

calcium leucovorin DRUG

calcium leucovorin (20 mg/m\^2) IV bolus, on Days 1, 8, 15

Also known as: Citrovorum Factor, Folinic Acid

FABLOx

oxaliplatin DRUG

oxaliplatin (40 mg/m\^2) as a 60-min IV infusion on Days 1, 8, and 15

Also known as: Elotaxin

FABLOx

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subject is between 18 and 65 years of age at the time of signing the Informed Consent Form (ICF).
• Subject has definitive histologically or cytologically confirmed metastatic pancreatic adenocarcinoma.
• Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.
• Subject has one or more tumors measurable by CT scan (or (MRI), if allergic to CT contrast media) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
• Subject has the following blood counts / Hemoglobin (Hgb) at screening:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L;
• Platelet count ≥ 100,000/mm3 (100 × 10\^9/L);
• Hgb ≥ LLN or 10 g/dL.
• Subject has the following blood chemistry levels at screening:
• AST (SGOT), ALT (SGPT) ≤ 2.5 x upper limit of normal range (ULN); if hepatic metastases present ≤ 5.0 x ULN
• Total bilirubin ≤ 1.5 X ULN
• Creatinine clearance ≥ 60 mL/min (by Cockroft-Gault)
• Albumin ≥ 3.5 grams/dL7.
• Females of childbearing potential (FOCBP) \[defined as a sexually mature woman who (1) have not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time during the preceding 24 consecutive months)\] must:
• Have a negative pregnancy test (β-human chorionic gonadotropin \[β -hCG\]) as verified by the study doctor within 72 hours prior to starting study therapy

You may not qualify if:

• Subject has received previous systemic chemotherapy or investigational therapy (other than that as a radiosensitizer concomitant with radiotherapy) for the treatment of pancreatic adenocarcinoma, including neo-adjuvant or adjuvant therapy.
• Subject has known brain metastases unless previously treated and controlled for a minimum of 2 weeks prior to enrollment. Subject is not receiving corticosteroids with no evidence of cerebral edema.
• Pre-existing peripheral neuropathy \> Grade 1
• Subject with unstable stent.
• History of malignancy in the last 3 years. Subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 3 years.
• Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy , defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.
• Subject has known historical or active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C or subject receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the Investigator, increase the risk of serious neutropenic complications.
• Subject has undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study or surgical wound has not fully healed.
• Subject has a history of allergy or hypersensitivity to any of the IP or any of their excipients, or the subject exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections for and of the products' Summary of Product Characteristics or Prescribing Information.
• History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).
• Subject with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies that in the opinion of the Investigator may put them at increased risk of interstitial pneumonitis.
• Subject with high cardiovascular risk, including, but not limited to:
• uncontrolled hypertension
• unstable angina
• diagnosis of ischemic heart disease

Sponsors & Collaborators

• Celgene: lead

Study Sites (7)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Tufts - New England Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Michigan

Ann Arbor, Michigan, 48103, United States

Location

Karmanos Cancer Center Wayne State University

Detroit, Michigan, 48201, United States

Location

Cornell University Weill Medical College

New York, New York, 10065, United States

Location

Gibbs Cancer Center and Research Institute

Spartanburg, South Carolina, 29303, United States

Location

Virginia Mason Cancer Center

Seattle, Washington, 98101, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenocarcinoma

Interventions

Fluorouracil; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Bevacizumab; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes

Study Officials

• Chrystal Louis, MD

  Celgene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2015
• First Posted: December 3, 2015
• Study Start: January 18, 2016
• Primary Completion: October 29, 2018
• Study Completion: October 29, 2018
• Last Updated: October 22, 2019

Record last verified: 2019-10

Locations

US (7)