Clinical Trials /

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

NCT03316599

Description:

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

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Gemcitabine, Nab-paclitaxel, and Ficlatuzumab (AV-299) in Patients With Advanced Pancreatic Cancer
  • Official Title: Phase 1b Study of Gemcitabine, Nab-paclitaxel, and Ficlatuzumab (AV-299) in Patients With Advanced Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17-406
  • NCT ID: NCT03316599

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
GemcitabineGemzarFiclatuzumab + Gemcitabine and Nab-Paclitaxel
Nab-paclitaxelAbraxaneFiclatuzumab + Gemcitabine and Nab-Paclitaxel
FiclatuzumabFiclatuzumab + Gemcitabine and Nab-Paclitaxel

Purpose

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

Detailed Description

      This research study is a Phase I dose-escalation clinical trial. It will test the safety and
      tolerability of an investigational drug ficlatuzumab when combined with Nab-paclitaxel and
      Gemcitabine, with the goal of determining the maximally tolerated dose of ficlatuzumab when
      combined with gemcitabine and nab-paclitaxel.

      Ficlatuzumab is a type of drug called a "monoclonal antibody." It is thought to work by
      targeting hepatocyte growth factor (HGF) which is a HGF-c-Met inhibitor. The activation of
      the receptor tyroside kinase c-Met via its ligand, HGF, mediates proliferation, motility, and
      differentiation in a variety of cancers including pancreatic cancer.

      Subjects must have a newly diagnosed stage 4 untreated metastatic pancreatic ductal cancer
      and meet all inclusion/exclusion criteria.

      Treatment consists of 4 week treatment cycles. Ficlatuzumab will be administered on day 1 and
      15 of each cycle. Nab-paclitaxel and gemcitabine will be administered on days 1,8, and 15.

      Subjects continue in study until disease progression, adverse event/toxicity, death or either
      the subject or sponsor discontinues the study.
    

Trial Arms

NameTypeDescriptionInterventions
Ficlatuzumab + Gemcitabine and Nab-PaclitaxelExperimentalFiclatuzumab 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.
  • Gemcitabine
  • Nab-paclitaxel
  • Ficlatuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  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

               -  Creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels
                  above 1.5 × upper limit of normal.

          -  Negative serum pregnancy test for women of childbearing potential.

          -  The effects of ficlatuzumab on the developing human fetus are unknown. For this reason
             and because Hepatocyte Growth Factor inhibitors as well as other therapeutic agents
             used in this trial are known to be teratogenic, women of child-bearing potential and
             men must agree to use adequate contraception (hormonal or barrier method of birth
             control; abstinence) prior to study entry, for the duration of study participation and
             4 months after completion of ficlatuzumab administration.. Should a woman become
             pregnant or suspect she is pregnant while she or her partner is participating in this
             study, she should inform her treating physician immediately.

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The Maximum Tolerated Dose of ficlatuzumab when administered in combination with gemcitabine and nab-paclitaxel
Time Frame:2 years
Safety Issue:
Description:Identify maximally tolerated dose of ficlatuzumab when administered in combination with gemcitabine and nab-paclitaxel

Secondary Outcome Measures

Measure:The response rate in this population of patients.
Time Frame:2 years
Safety Issue:
Description:Determine the number of patients who demonstrate a clinical response assessed by RECIST criteria on imaging to the combination of ficlatuzumab with gemcitabine and nab-paclitaxel.
Measure:The progression free survival in this population of patients.
Time Frame:2 years
Safety Issue:
Description:Determine the progression free survival derived from the combination of ficlatuzumab with gemcitabine and nab-paclitaxel.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Pancreatic Cancer

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