Clinical Trials /

Chemotherapy With Nab-paclitaxel/Germcitabine/Cisplatin +/- BGB324 With Pancreatic Cancer

NCT03649321

Description:

Determine the complete response (CR) rate of bemcentinib plus chemotherapy (nab-paclitaxel/gemcitabine/cisplatin) in patients with metastatic pancreatic adenocarcinoma.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Chemotherapy With Nab-paclitaxel/Germcitabine/Cisplatin +/- BGB324 With Pancreatic Cancer
  • Official Title: A phase1b/2 Randomized Clinical Trial of Chemotherapy With Nab-paclitaxel/Gemcitabine/Cisplatin +/- the AXL-inhibitor Bemcentinib for Patients With Metastatic Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: STU 062018-024
  • NCT ID: NCT03649321

Conditions

  • Cancer of Pancreas

Interventions

DrugSynonymsArms
BGB324BemcentinibPart 1 - Safety Run
Nab-paclitaxelPart 1 - Safety Run
GemcitabinePart 1 - Safety Run
CisplatinPart 1 - Safety Run

Purpose

Determine the complete response (CR) rate of bemcentinib plus chemotherapy (nab-paclitaxel/gemcitabine/cisplatin) in patients with metastatic pancreatic adenocarcinoma.

Detailed Description

      Bemcentinib inhibits pancreatic cancer proliferation as monotherapy and in combination with
      gemcitabine through inhibition of the Axl pathway. The combination of
      nab-paclitaxel/gemcitabine/cisplatin has encouraging signs of clinical activity in patients
      with metastatic pancreatic cancer38. We would like to build on this combination in a
      biomarker driven phase 1b/2 clinical trial of bemcentinib in
      nab-paclitaxel/gemcitabine/cisplatin for patients with metastatic pancreatic cancer.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1 - Safety RunExperimentalBGB324 200 mg oral daily, plus chemotherapy. Nab-paclitaxel 125 mg/m^2 Day 1 /8 every 21 days. Gemcitabine 1000 mg/m^2 Day 1 /8 every 21 days. Cisplatin 25 mg/m^2 Day 1 /8 every 21 days.
  • BGB324
  • Nab-paclitaxel
  • Gemcitabine
  • Cisplatin
Part 2 - BGB324 plus chemotherapyExperimentalBGB324 200 mg oral daily. Nab-paclitaxel 125 mg/m^2 Day 1 /8 every 21 days. Gemcitabine 1000 mg/m^2 Day 1 /8 every 21 days. Cisplatin 25 mg/m^2 Day 1 /8 every 21 days.
  • BGB324
  • Nab-paclitaxel
  • Gemcitabine
  • Cisplatin
Part 2 - Chemotherapy AloneExperimentalNab-paclitaxel 125 mg/m^2 Day 1 /8 every 21 days. Gemcitabine 1000 mg/m^2 Day 1 /8 every 21 days. Cisplatin 25 mg/m^2 Day 1 /8 every 21 days.
  • Nab-paclitaxel
  • Gemcitabine
  • Cisplatin

Eligibility Criteria

        Inclusion Criteria:

          1. Ability to understand and the willingness to sign a written informed consent.

          2. Patients must have a histologically or cytologically confirmed pancreatic
             adenocarcinoma that is metastaticor recurrent.

          3. No prior systemic therapy for metastatic or recurrent disease.

               -  Prior adjuvant gemcitabine, if completed more than 12 months prior to date of
                  enrollment, is acceptable.

               -  Radiosensitizing chemotherapy, if completed at least 4 weeks from date of
                  enrollment, is acceptable.

          4. Measurable disease is required per RECIST1.1 criteria.

          5. Age 18-70 years at the time of enrollment.

        7. ECOG performance status 0 or 1. 8. Have resolution of toxic effect(s) of the most recent
        prior chemotherapy to Grade 1 or less (except alopecia). If the patient received major
        surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or
        complications from the intervention.

        9. Adequate hematologic, hepatic, and renal function. All screening labs should be
        performed within 14 days of registration.

        10. Female patients of childbearing potential must have a negative pregnancy test (either
        urine or serum pregnancy test) within 72 hours prior to the first dose of study treatment.
        If the urine pregnancy test is positive or cannot be confirmed as negative, a serum
        pregnancy test will be required. A female of child-bearing potential is any woman
        (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate
        by choice) who meets the following criteria:

          -  Has not undergone a hysterectomy or bilateral oophorectomy; or

          -  Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has
             had menses at any time in the preceding 12 consecutive months).

             11. 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 for 120 days following completion of therapy.
             Should a woman become pregnant or suspect she is pregnant while participating in this
             study, she should inform her treating physician immediately.

        Exclusion Criteria:

          1. Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of study treatment.

          2. Patients with known untreated brain metastases. Patients without known brain
             metastases do not require radiologic imaging prior to enrollment.

          3. Has a known additional malignancy that is progressing or requires active treatment.
             Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of
             the skin that has undergone potentially curative therapy or in situ cervical cancer.

          4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, significant pulmonary disease (shortness of breath at rest or mild
             exertion), or uncontrolled infection or psychiatric illness/social situations that
             would limit compliance with study requirements.

          5. History of the following cardiac conditions:

               1. Congestive cardiac failure of >Grade II severity according to the NYHA (defined
                  as symptomatic at less than ordinary levels of activity);

               2. Ischemic cardiac event including myocardial infarction within 3 months prior to
                  date of enrollment

               3. Uncontrolled cardiac disease, including unstable angina pectoris, uncontrolled
                  hypertension (i.e. sustained systolic BP >160 mmHg or diastolic BP >90 mmHg),
                  cardiac arrhythmia, or need to change medication due to lack of disease control
                  within 6 weeks prior to date of enrollment;

               4. History or presence of sustained bradycardia (≤55 BPM), left bundle branch block,
                  cardiac pacemaker or ventricular arrhythmia. Note: Patients with a
                  supraventricular arrhythmia requiring medical treatment, but with a normal
                  ventricular rate are eligible;

               5. Known family history or personal history of long QTc syndrome or previous
                  drug-induced QTc prolongation of at least Grade 3 (QTc >500 ms).

          6. Abnormal left ventricular ejection fraction (LVEF) on echocardiography or MUGA (less
             than the lower limit of normal for a patient of that age at the treating institution
             or <45%).

          7. Current treatment with any agent known to cause Torsades de Pointes which cannot be
             discontinued at least five half-lives or two weeks prior to the first dose of study
             treatment.

          8. Screening 12-lead ECG with a measurable QTc interval according to Fridericia's
             correction >450 ms.

          9. Known active infection with human immunodeficiency virus (HIV), hepatitis B or C
             viruses (screening not required, follow institutional practice):

               1. Patients who have a history of hepatitis B infection are eligible provided they
                  are hepatitis B surface antigen negative.

               2. Patients who have a history of hepatitis C infection are eligible provided they
                  have no evidence of hepatitis C ribonucleic acid using a quantitative polymerase
                  chain reaction assay at least 6 months after completing treatment for hepatitis C
                  infection.

         10. Active, clinically significant serious infection requiring treatment with antibiotics,
             anti-virals or anti-fungals.

         11. Treatment with any medication which is predominantly metabolized by CYP3A4 and has a
             narrow therapeutic index.

         12. Major surgery within 4 weeks prior to date of enrollment; excluding skin biopsies and
             procedures for insertion of central venous access devices.

         13. Inability to tolerate oral medication.

         14. Existing gastrointestinal disease affecting drug absorption such as celiac disease or
             Crohn's disease, or previous bowel resection which is considered to be clinically
             significant or could interfere with absorption.

         15. Known lactose intolerance.

         16. Treatment with any of the following: histamine receptor 2 inhibitors, proton pump
             inhibitors or antacids within 7 days of start of study treatment.

         17. Continuous treatment with more than 40 mg prednisolone (or equivalent dose of systemic
             corticosteroid) which cannot be discontinued up to one week prior to starting
             bemcentinib.

         18. Is pregnant or breastfeeding.

         19. Any significant medical condition lab abnormality, or psychiatric illness, in the
             opinion of the investigator, that might interfere with the patient's participation in
             the study or in the evaluation of the study results.

         20. Unwillingness or inability to comply with study procedures.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Response Rate (CR)
Time Frame:Every 4 months from time of first dose of study drug until completion of treatment for approximately 100 months..
Safety Issue:
Description:Determine the complete response (CR) rate of bemcentinib plus chemotherapy (nab-paclitaxel/gemcitabine/cisplatin) in patients with metastatic pancreatic adenocarcinoma.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

Last Updated

January 31, 2020