Clinical Trials /

Study of Nintedanib and Chemotherapy for Advanced Pancreatic Cancer

NCT02902484

Description:

The study will perform a clinical study evaluating the safety and tolerability of nintedanib when combined with standard chemotherapy (Gemcitabine + nab-Paclitaxel) for metastatic pancreatic cancer. It will utilize advanced imaging correlates including dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) which correlates with tumor grade and microvessel density.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Nintedanib and Chemotherapy for Advanced Pancreatic Cancer
  • Official Title: A Phase 1b and Pharmacodynamic Study of Nintedanib Monotherapy for Advanced Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: STU 022016-083
  • NCT ID: NCT02902484

Conditions

  • Cancer of Pancreas

Interventions

DrugSynonymsArms
NintedanibOfev, VargatefNintedanib Monotherapy

Purpose

The study will perform a clinical study evaluating the safety and tolerability of nintedanib when combined with standard chemotherapy (Gemcitabine + nab-Paclitaxel) for metastatic pancreatic cancer. It will utilize advanced imaging correlates including dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) which correlates with tumor grade and microvessel density.

Detailed Description

      Preclinical data suggest nintedanib inhibits primary tumor growth in in vivo xenograft
      models of pancreatic cancer, as well as inhibiting metastasis in pancreatic cancer models.
      This effect appears primarily due to nintedanib anti-angiogenic properties. The study will
      perform a clinical study evaluating the safety and tolerability of nintedanib when combined
      with standard chemotherapy (Gemcitabine + nab-Paclitaxel) for metastatic pancreatic cancer.
      It will utilize advanced imaging correlates including dynamic contrast enhanced Magnetic
      Resonance Imaging (DCE-MRI) which correlates with tumor grade and microvessel density.

      For each patient, treatment will have two phases: nintedanib monotherapy for a two week
      period (Days 1-14) followed by combination phase of nintedanib plus chemotherapy (Cycle 2+).
    

Trial Arms

NameTypeDescriptionInterventions
Nintedanib MonotherapyExperimentalOne cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. Nintedanib dose escalation: 150, 200 mg PO BID Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days
  • Nintedanib

Eligibility Criteria

        Inclusion Criteria:

          1. Signed and dated written informed consent prior to admission to the study;

          2. Histologically or cytologically confirmed metastatic or locally advanced
             adenocarcinoma of the pancreas;

          3. At least one measurable disease lesion according to Response Evaluation Criteria In
             Solid Tumors (RECIST, version 1.1);

          4. Age ≥ 18 years;

          5. No more than one prior line of non-gemcitabine/nab-paclitaxel containing systemic
             therapy for metastatic/locally advanced pancreatic cancer;

          6. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1;

          7. Women of childbearing potential must have a negative pregnancy test (urine or serum)
             within 14 days prior to registration; (Note: contraception in patients with
             reproductive capacity will be considered to be of childbearing potential unless
             surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or
             post-menopausal for at least two years.)

          8. Adequate biological parameters at baseline (obtained within 14 days prior to
             registration).

          9. If elevated liver function tests develop at the time of initial presentation or
             develop during workup and are the result of mechanical obstruction of the biliary
             drainage by tumor compression or invasion, a biliary drain may be placed. If drainage
             allows the liver function tests to come within inclusion criteria, the patient may be
             enrolled.

        Exclusion Criteria:

          1. More than one systemic therapy regimen of any type for metastatic or locally advanced
             disease. Adjuvant gemcitabine that ended more than 6 months from diagnosis of
             recurrent disease is not considered as a regimen;

          2. Prior treatment with nintedanib or any other VEGFR inhibitor;

          3. Known hypersensitivity to nintedanib, gemcitabine and nab-Paclitaxal peanut or soya
             or any other trial drug, their excipients or to contrast media;

          4. Chemo-, hormon-, radio-(except for brain and extremities) or immunotherapy or therapy
             with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4
             weeks prior to treatment with the trial drug;

          5. Radiotherapy to the target lesion within the past 3 months prior to baseline imaging

          6. Persistence of clinically relevant therapy related toxicity from previous chemo
             and/or radiotherapy;

          7. Active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment
             with radiotherapy, symptomatic, requiring treatment with anti-convulsants;
             dexamethasone therapy will be allowed if administered as stable dose for at least one
             month before randomization);

          8. Leptomeningeal disease;

          9. Radiographic evidence of cavitary or necrotic tumors;

         10. Treatment with other investigational drugs or treatment in another clinical trial
             within the past 4 weeks before start of therapy or concomitantly with the trial;

         11. Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose
             heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous
             devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic
             acid < 325mg per day);

         12. Major injuries and/or surgery within the past 4 weeks prior to start of study
             treatment with incomplete wound healing and/or planned surgery during the
             on-treatment study period;

         13. History of clinically significant hemorrhagic or thromboembolic event in the past 6
             months;

         14. Known inherited predisposition to bleeding or thrombosis;

         15. Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable
             angina, history of infarction within the past 12 months prior to start of study
             treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia,
             pericardial effusion);

         16. Proteinuria CTCAE grade 2 or greater;

         17. Creatinine > 1.5 x ULN or GFR < 45 mL/min;

         18. Hepatic function: total bilirubin outside of normal limits; ALT or AST > 1.5 ULN in
             pts without liver metastasis. For Pts with liver metastasis: total bilirubin outside
             of normal limits, ALT or AST > 2.5 ULN;

         19. Coagulation parameters: International Normalized Ratio (INR) > 2, prothrombin time
             (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN;

         20. Absolute neutrophil count (ANC) < 1500/mL, platelets < 100,000/mL, Hemoglobin < 9.0
             g/dl;

         21. Any known active cancer other than pancreatic primary;

         22. Active serious infections in particular if requiring systemic antibiotic or
             antimicrobial therapy;

         23. Active or chronic hepatitis C and/or B infection;

         24. Gastrointestinal disorders or abnormalities that would interfere with absorption of
             the study drug;

         25. Serious illness or concomitant non-oncological disease such as neurologic,
             psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or
             laboratory abnormality that may increase the risk associated with study participation
             or study drug administration and in the judgment of the investigator would make the
             patient inappropriate for entry into the study;

         26. Pregnancy or breast feeding female;

         27. Psychological, familial, sociological or geographical factors potentially hampering
             compliance with the study protocol and follow-up schedule;

         28. Active alcohol or drug abuse;

         29. Significant weight loss (> 20% of BW) within past 6 months prior to inclusion into
             the trial or actual body weight of less than 50 kg;

         30. Patients who are sexually active and unwilling to use a medically acceptable method
             of contraception (e.g. such as implants, injectable, combined oral contraceptives,
             some intrauterine devices, sexual abstinence or vasectomized partner for
             participating females, condoms for participating males) during the trial and for at
             least three months after end of active therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:Each 28 day cycle for 2 years
Safety Issue:
Description:A standard 3+3 phase 1 trial design will be used for Nintedanib monotherapy for a two week period (Days 1-14) followed by combination phase of nintedanib plus chemotherapy. Two dose levels of nintedanib will be explored 150 mg IBD and 200 mg BID. The combination phase will include gemcitabine + nab-paclitaxel, and nintedanib. Patient treatment will consist of gemcitabine 1000 mg/m & nab-paclitaxel 120 mg/m. Treatment will be administered intravenously on days 1, 8, 15 every 28 days.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

Last Updated

November 22, 2016