Study of Gemcitabine, Nab-paclitaxel, and Ficlatuzumab (AV-299) in Patients With Advanced Pancreatic Cancer

NCT03316599 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 17-406
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

To identify the maximally tolerated dose of ficlatuzumab when combined with nab-paclitaxel and gemcitabine in patients with previously untreated pancreatic cancer.

Conditions

Pancreatic Cancer

Keywords

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• The Maximum Tolerated Dose of ficlatuzumab when administered in combination with gemcitabine and nab-paclitaxel

  Identify maximally tolerated dose of ficlatuzumab when administered in combination with gemcitabine and nab-paclitaxel

  2 years

Secondary Outcomes (2)

• The response rate in this population of patients.

  2 years

• The progression free survival in this population of patients.

  2 years

Study Arms (1)

Ficlatuzumab + Gemcitabine and Nab-Paclitaxel

EXPERIMENTAL

* Ficlatuzumab will be administered intravenously days 1 and 15 of a 28 day cycle * Gemcitabine 1000 mg/m2 and Nab-Paclitaxel 125mg/m2 will be administered IV days 1, 8, and 15 of a 28 day cycle. * Dosage of Ficlatuzumab is determined by dose level to which the patient is assigned at time of enrollment.

Drug: Gemcitabine; Drug: Nab-paclitaxel; Drug: Ficlatuzumab

Interventions

Gemcitabine DRUG

Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Also known as: Gemzar

Ficlatuzumab + Gemcitabine and Nab-Paclitaxel

Nab-paclitaxel DRUG

Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells

Also known as: Abraxane

Ficlatuzumab + Gemcitabine and Nab-Paclitaxel

Ficlatuzumab DRUG

It is selective recombinant humanized hepatocyte growth factor (HGF) inhibitory immunoglobulin G subclass 1 monoclonal antibody which blocks the MET tyrosine kinase receptor.

Ficlatuzumab + Gemcitabine and Nab-Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Cytologically- or histologically-confirmed pancreatic adenocarcinoma or poorly differentiated pancreatic carcinoma that is metastatic to distant sites.
• Other histologies such as neuroendocrine and acinar cell carcinoma are excluded.
• No prior chemotherapy for locally advanced or metastatic pancreatic cancer.
• Patients are eligible if they received adjuvant treatment after surgical resection with single-agent gemcitabine or gemcitabine/capecitabine or 5-fluorouracil/leucovorin that was completed \>12 months before enrollment. Similarly, adjuvant radiation +/- chemosensitization with 5-fluorouracil, capecitabine, or gemcitabine is allowed if completed \>12 months before enrollment.
• Participants are required to have measurable disease (RECIST v1.1), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10 mm with spiral CT scan. See section 11 for the evaluation of measurable disease.
• Participants enrolled must have disease that is accessible for tumor biopsies and must agree to a pre-treatment tumor biopsy.
• Age ≥ 18 years. Because no dosing or adverse event data are currently available in participants \<18 years of age, children are excluded from this study but will be eligible for future pediatric trials.
• ECOG performance status ≤2 (see Appendix A)
• Patients must have completed any major surgery or open biopsy ≥4 weeks from start of treatment.
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Total bilirubin ≤1.5 × institutional upper limit of normal
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
• Creatinine ≤1.5 × institutional upper limit of normal OR

You may not qualify if:

• Prior chemotherapy or any other investigational agents for the treatment of locally advanced or metastatic pancreatic cancer
• Concurrent use of any other anti-cancer therapy, including chemotherapy, targeted therapy, immunotherapy, or biological agents.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Screening for brain metastases with head imaging is not required.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ficlatuzumab or other agents used in study.
• History of prior or current synchronous malignancy, except:
• Malignancy that was treated with curative intent and for which there has been no known active disease for \>3 years prior to enrollment
• Curatively treated non-melanoma skin cancer, cervical cancer in situ, or prostatic intraepithelial neoplasia, without evidence of prostate cancer
• Pre-existing, clinically significant peripheral neuropathy, defined as CTCAE grade 2 or higher neurosensory or neuromotor toxicity, regardless of etiology
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, NYHA class III/IV congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because ficlatuzumab is hepatocyte growth factor inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ficlatuzumab, breastfeeding should be discontinued if the mother is treated with ficlatuzumab. These potential risks may also apply to other agents used in this study

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• AVEO Pharmaceuticals, Inc.: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; ficlatuzumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Kimberly Perez, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 14, 2017
• First Posted: October 20, 2017
• Study Start: January 17, 2018
• Primary Completion: October 10, 2020
• Study Completion: July 29, 2021
• Last Updated: August 3, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)