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Bemcentinib with Nab-Paclitaxel, Gemcitabine, and Cisplatin in Treating Patients with Metastatic or Recurrent Pancreatic Cancer

Trial Status: Active

This phase Ib / II trial studies how well bemcentinib in combination with nab-paclitaxel, gemcitabine, and cisplatin work in treating patients with pancreatic cancer that has spread to other places in the body or that has come back. Bemcentinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as nab-paclitaxel, gemcitabine, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bemcentinib with nab-paclitaxel, gemcitabine, and cisplatin may work better in treating patients with pancreatic cancer.

Inclusion Criteria

  • Ability to understand and the willingness to sign a written informed consent
  • Patients must have a histologically or cytologically confirmed pancreatic adenocarcinoma that is metastatic or recurrent
  • 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
  • Measurable disease is required per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • 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
  • Hemoglobin >= 10 g/dL (within 14 days of registration)
  • Absolute neutrophil count (ANC) >= 1,500/uL (within 14 days of registration)
  • Platelets >= 100,000/uL (within 14 days of registration)
  • Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (within 14 days of registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN in patients without known liver metastasis; =< 5 x institutional ULN in patients with known liver metastasis (within 14 days of registration)
  • Serum creatinine =< 1.5 times ULN, and calculated creatinine clearance >= 60 mL/min using the Cockcroft-Gault equation) (within 14 days of registration)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 times the ULN (within 14 days of registration)
  • Lactate dehydrogenase (LDH) =< 2.5 times the ULN (within 14 days of registration)
  • Albumin >= 3.0 g/dL (within 14 days of registration)
  • 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)
  • 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

  • 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
  • Patients with known untreated brain metastases. Patients without known brain metastases do not require radiologic imaging prior to enrollment
  • 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
  • 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
  • History of the following cardiac conditions: * Congestive cardiac failure of > Grade II severity according to the New York Heart Association (NYHA) (defined as symptomatic at less than ordinary levels of activity) * Ischemic cardiac event including myocardial infarction within 3 months prior to date of enrollment * Uncontrolled cardiac disease, including unstable angina pectoris, uncontrolled hypertension (i.e. sustained systolic blood pressure [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 * History or presence of sustained bradycardia (=< 55 beats per minute [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 * Known family history or personal history of long corrected QT (QTc) syndrome or previous drug-induced QTc prolongation of at least Grade 3 (QTc > 500 ms)
  • Abnormal left ventricular ejection fraction (LVEF) on echocardiography or multigated acquisition (MUGA) (less than the lower limit of normal for a patient of that age at the treating institution or < 45%)
  • 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
  • Screening 12-lead electrocardiogram (ECG) with a measurable QTc interval according to Fridericia’s correction > 450 ms
  • Known active infection with human immunodeficiency virus (HIV), hepatitis B or C viruses (screening not required, follow institutional practice): * Patients who have a history of hepatitis B infection are eligible provided they are hepatitis B surface antigen negative * 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
  • Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals
  • Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index
  • Major surgery within 4 weeks prior to date of enrollment; excluding skin biopsies and procedures for insertion of central venous access devices
  • Inability to tolerate oral medication
  • 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
  • Known lactose intolerance
  • Treatment with any of the following: histamine receptor 2 inhibitors, proton pump inhibitors or antacids within 7 days of start of study treatment
  • 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
  • Is pregnant or breastfeeding
  • 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
  • Unwillingness or inability to comply with study procedures

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Muhammad Shaalan Beg
Phone: 214-648-4180

PRIMARY OBJECTIVES:

I. Determine the clinical activity as defined by complete response (CR) rate of AXL inhibitor BGB324 (bemcentinib) plus chemotherapy (nab-paclitaxel/gemcitabine/cisplatin) in patients with metastatic pancreatic adenocarcinoma.

SECONDARY OBJECTIVES:

I. Determine clinical activity of bemcentinib plus chemotherapy as defined by overall response rate (ORR), median progression free survival (PFS), 1-year and 2-year overall survival (OS) rate.

II. Assess safety and tolerability of bemcentinib plus chemotherapy in patients with metastatic pancreatic adenocarcinoma.

III. Determine impact of therapy on Quality of life (QOL).

EXPLORATORY OBJECTIVES:

I. Compare the effect of treatment, with chemotherapy alone vs chemotherapy + Axl inhibitor bemcentinib (bemcentinib) on changes in tissue and blood biomarkers.

II. Correlate changes in tissue and blood biomarkers with clinical outcomes (ORR).

OUTLINE: This is a phase Ib, dose-escalation study of bemcentinib, followed by a phase II study.

SAFETY RUN-IN: Patients receive AXL inhibitor BGB324 orally (PO) once daily (QD) beginning on day 2 of cycle 1. Patients also receive nab-paclitaxel intravenously (IV) over 30 minutes on days 1 and 8, cisplatin IV over 60 minutes on days 1 and 8, and gemcitabine IV over 30 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive AXL inhibitor BGB324 PO QD beginning on day 2 of cycle 1. Patients also receive nab-paclitaxel IV over 30 minutes on days 1 and 8, cisplatin IV over 60 minutes on days 1 and 8, and gemcitabine IV over 30 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients also receive nab-paclitaxel IV over 30 minutes on days 1 and 8, cisplatin IV over 60 minutes on days 1 and 8, and gemcitabine IV over 30 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 4 months thereafter.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
UT Southwestern / Simmons Cancer Center-Dallas

Principal Investigator
Muhammad Shaalan Beg

  • Primary ID SCCC08218
  • Secondary IDs NCI-2019-00143, STU 062018-024
  • Clinicaltrials.gov ID NCT03649321