Clinical Trials /

Nab-Paclitaxel + Cisplatin + Gemcitabine + TTF in pt. w/ Metastatic PAC

NCT04605913

Description:

This is a Phase I/Ib trial, single-center, non-randomized, open-label study of Protein-bound Paclitaxel, Cisplatin, And Gemcitabine (GCN) Combined with Tumor Treatment Fields (TTF) and G+TTF maintenance therapy in patients with metastatic pancreatic cancer.

Related Conditions:
  • Pancreatic Adenocarcinoma
  • Pancreatic Adenosquamous Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nab-Paclitaxel + Cisplatin + Gemcitabine + TTF in pt. w/ Metastatic PAC
  • Official Title: A Phase I/Ib Pilot Trial of Protein-bound Nab-Paclitaxel, Cisplatin, And Gemcitabine (GCN) Combined With Tumor Treatment Fields (TTF) in Patient With Metastatic Pancreatic Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: 2009038851
  • NCT ID: NCT04605913

Conditions

  • Pancreas Cancer
  • Metastatic Pancreatic Cancer
  • Pancreatic Adenocarcinoma
  • Metastatic Adenocarcinoma

Purpose

This is a Phase I/Ib trial, single-center, non-randomized, open-label study of Protein-bound Paclitaxel, Cisplatin, And Gemcitabine (GCN) Combined with Tumor Treatment Fields (TTF) and G+TTF maintenance therapy in patients with metastatic pancreatic cancer.

Detailed Description

      GCN is predicted to be the front-line therapy for biliary and pancreatic cancer in the future
      given excellent results of current early clinical trials (ORR ≥ 67% in pancreatic cancer).
      This will change standard of care for front-line therapy in patients with stage IV pancreatic
      cancer. In this cohort of patients' tolerability after 6 cycles of therapy will be a
      challenge. Investigators hypothesize that developing a maintenance strategy with TTF+G will
      be cutting edge approach and can potentially transform front-line standard of care therapy in
      patients with stage IV pancreatic cancer. If this pilot study proves fruitful then a larger
      study to confirm findings can be conducted.
    

Trial Arms

NameTypeDescriptionInterventions
Modified GCN+TTF treatmentExperimentalThe trial will compose of 2 parts with a total of 40 subjects. The regimen will consist of gemcitabine (G) administered at a dose of 800 mg/m2, cisplatin (C) 30 mg/m2, and protein-bound paclitaxel (N) 150 mg/m2 administered on cycle 1 day 1 and every 2 weeks thereafter and TTF will be administered daily (150kHz 18 hours/day) starting with Cycle 1 Day 1 (dose level 1). After completing 6 cycles, patients will then transition to a maintenance phase of G administered at a dose of 1000 mg/m2 every 2 weeks and daily TTF (150 KHZ 18 hours/day) until progression of disease (POD) per RECIST v1.1. If 6 patients tolerate the dose level of GCN+TTF through the 1st cycle without defined dose limiting toxicities (DLTs) or grade 4 treatment related adverse events (TRAE), the 2nd part of the study (phase Ib portion) will commence. An additional 34 patients will be enrolled in the expansion cohort (phase Ib).

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Histologically or cytologically confirmed pancreatic adenocarcinoma or adeno-squamous
                 carcinoma with liver metastasis.
    
                   1. Subjects with additional sites of metastasis, except known brain metastasis, are
                      eligible.
    
                   2. Histologies excluded include squamous, small cell carcinoma, and acinar cell
                      carcinoma. However, adeno-squamous histology can be enrolled.
    
                   3. Patients who have recurrence or metastasis after surgery and adjuvant therapy do
                      not need repeat biopsy for confirmation of recurrence if clinical suspicion is
                      high per scans (MRI/CT scan), with and without CA 19-9 elevation, specifically if
                      biopsy is unsafe or technically difficult.
    
              2. Patients with no prior lines of therapy for the treatment of stage IV metastatic
                 disease.
    
                   1. Patients could have had prior neoadjuvant or adjuvant chemotherapy or
                      chemo-radiotherapy.
    
                 i. Patients who received gemcitabine-based adjuvant chemotherapy can enroll if they
                 progress greater than 6 months after completion of the therapy; ii. Patients who
                 progress while on adjuvant FOLFIRINOX can enroll immediately.
    
              3. Male and female patients at least 18 years of age
    
              4. Laboratory data as specified below:
    
                 Hematology:
    
                 - ANC greater than 1500 cells/mm3,
    
                 - platelet count greater than 100,000 cells/mm3, and
    
                 - Hemoglobin greater than 8 g/dL.
    
                   -  Hepatic
    
                        -  Direct bilirubin less than 1.5 X ULN;
    
                        -  alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than
                           3 X ULN.
    
                 For patients with known liver metastases or liver neoplasms: alanine aminotransferase
                 (ALT) or aspartate aminotransferase (AST) less than 6.0 X ULN and direct bilirubin
                 less than 3 x ULN.
    
                   -  Renal:
    
                        -  serum creatinine WNL or creatinine clearance greater than 50 mL/min.
    
              5. QT intervals: QTc less than or equal to 470 msec for men and less than or equal to 490
                 msec for women. (As measured by Hodges' Equation: QTc = QT + 1.75(rate-60) where QTc =
                 corrected QT interval and rate = ventricular rate/min).
    
              6. Estimated life expectancy of at least 3 months
    
              7. ECOG Performance Status 0-1.
    
              8. Ability to operate the Novo TTF-100L (P) system.
    
              9. Patients must have measurable disease on scans per RECIST 1.1.
    
             10. Negative serum pregnancy test within 14 days prior to the first dose of study therapy
                 for women of child-bearing potential (WCBP), defined as a sexually mature woman who
                 has not undergone a hysterectomy or who has not been naturally post-menopausal for at
                 least 24 consecutive months (i.e., who has had menses any time in the preceding 24
                 consecutive months). Sexually active WCBP and male subjects must agree to use adequate
                 methods to avoid pregnancy (oral, injectable, or implantable hormonal contraceptive;
                 tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or
                 vasectomized partner) throughout the study and for 28 days after the completion of
                 study treatment.
    
            Exclusion Criteria:
    
            1. Previous front-line therapy for metastatic disease.
    
              1. Patients with known brain metastasis.
    
              2. Cardiac conduction abnormalities such as 2nd and 3rd heart-block requiring a
                 pacemaker.
    
              3. Patient with cardiac or abdominal pacemakers or stimulators.
    
              4. Significant risk of cardiac drug toxicity due to congestive heart failure or history
                 of myocardial infarction.
    
              5. Any other condition including but not limited to major co-morbidities, which in the
                 opinion of the investigator would render the patient ineligible.
    
              6. Concomitant use of drugs that have black box warning of Torsades de Pointes will also
                 be prohibited if cannot be replaced by another drug.
    
              7. Known sensitivity to conductive hydrogels.
    
            10. Patients who are pregnant or breastfeeding.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Determine safety of (m)-GCN+TTF
    Time Frame:28 days
    Safety Issue:
    Description:To determine the safety of modified (m)-GCN+TTF in patients with recurrent and/or metastatic pancreatic cancer (met-PC) by measuring grade 4 treatment related adverse events (TRAE).

    Secondary Outcome Measures

    Measure:Progression-free Survival
    Time Frame:Six months
    Safety Issue:
    Description:
    Measure:Overall Response Rate
    Time Frame:Six months
    Safety Issue:
    Description:Objective responses in tumor size will be evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).
    Measure:Overall Survival
    Time Frame:Twelve months
    Safety Issue:
    Description:

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University of Arizona

    Trial Keywords

    • GCN
    • TTF
    • Paclitaxel
    • Cisplatin
    • Gemcitabine
    • Tumor Treatment Fields

    Last Updated

    January 12, 2021