Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03649321
Recruitment Status : Recruiting
First Posted : August 28, 2018
Last Update Posted : January 10, 2019
Sponsor:
Collaborators:
Triligent International
Translational Genomics Research Institute
BerGenBio ASA
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

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

Condition or disease Intervention/treatment Phase
Cancer of Pancreas Drug: BGB324 Drug: Nab-paclitaxel Drug: Gemcitabine Drug: Cisplatin Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 3, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1 - Safety Run
BGB324 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.
Drug: BGB324
Bemcentinib is a small molecule, orally bioavailable, highly specific inhibitor of Axl kinase.
Other Name: Bemcentinib

Drug: Nab-paclitaxel
25 mg/m^2 Day 1 /8 every 21 days.

Drug: Gemcitabine
Gemcitabine 1000 mg/m^2 Day 1 /8 every 21 days

Drug: Cisplatin
Cisplatin 25 mg/m^2 Day 1 /8 every 21 days

Experimental: Part 2 - BGB324 plus chemotherapy
BGB324 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.
Drug: BGB324
Bemcentinib is a small molecule, orally bioavailable, highly specific inhibitor of Axl kinase.
Other Name: Bemcentinib

Drug: Nab-paclitaxel
25 mg/m^2 Day 1 /8 every 21 days.

Drug: Gemcitabine
Gemcitabine 1000 mg/m^2 Day 1 /8 every 21 days

Drug: Cisplatin
Cisplatin 25 mg/m^2 Day 1 /8 every 21 days

Experimental: Part 2 - Chemotherapy Alone
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.
Drug: Nab-paclitaxel
25 mg/m^2 Day 1 /8 every 21 days.

Drug: Gemcitabine
Gemcitabine 1000 mg/m^2 Day 1 /8 every 21 days

Drug: Cisplatin
Cisplatin 25 mg/m^2 Day 1 /8 every 21 days




Primary Outcome Measures :
  1. 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.. ]
    Determine the complete response (CR) rate of bemcentinib plus chemotherapy (nab-paclitaxel/gemcitabine/cisplatin) in patients with metastatic pancreatic adenocarcinoma.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03649321


Contacts
Layout table for location contacts
Contact: Simmons Cancer Center CRO Office 214-648-7097 ResearchRegistry@UTSouthwestern.edu
Contact: Kimberli Crane, MS, CCRP 214-648-7029 Kimberli.Crane@UTSouthwestern.edu

Locations
Layout table for location information
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390-9179
Contact: Kimberli Crane    214-648-7029    kimberli.crane@utsouthwestern.edu   
Principal Investigator: Muhammad Beg, MD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Triligent International
Translational Genomics Research Institute
BerGenBio ASA
Investigators
Layout table for investigator information
Principal Investigator: Muhammas S Beg, MD University of Texas Southwestern Medical Center

Layout table for additonal information
Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT03649321     History of Changes
Other Study ID Numbers: STU 062018-024
First Posted: August 28, 2018    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
Gemcitabine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs