Clinical Trials /

Study of Lonsurf in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced (PDAC)

NCT04046887

Description:

The purpose of this study is to determine the recommended phase 2 dose (RP2D) of the combination of lonsurf, gemcitabine and nab-paclitaxel in Pancreatic ductal adenocarcinoma (PDAC)

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Lonsurf in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced (PDAC)
  • Official Title: Phase I Study of Lonsurf in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced Pancreatic Ductal Adenocarcinoma (PDAC)

Clinical Trial IDs

  • ORG STUDY ID: IUSCC-0664
  • NCT ID: NCT04046887

Conditions

  • Pancreatic Cancer
  • Pancreatic Ductal Adenocarcinoma

Interventions

DrugSynonymsArms
LonsurfCombination of lonsurf + gemcitabine + nab-paclitaxel
GemcitabineCombination of lonsurf + gemcitabine + nab-paclitaxel
Nab-PaclitaxelCombination of lonsurf + gemcitabine + nab-paclitaxel

Purpose

The purpose of this study is to determine the recommended phase 2 dose (RP2D) of the combination of lonsurf, gemcitabine and nab-paclitaxel in Pancreatic ductal adenocarcinoma (PDAC)

Detailed Description

      This is a single-institution, prospective, phase I dose escalation trial of lonsurf combined
      with gemcitabine and nab-paclitaxel using the 3+3 design. This study will enroll 18 patients
      over 12-15 months.

      Primary Objective To determine the recommended phase 2 dose (RP2D) of the combination of
      lonsurf, gemcitabine and nab-paclitaxel

      Secondary Objectives

        1. Examine safety and toxicity of the combination

        2. Estimate response rate to the combination

        3. Estimate median overall survival (mOS) of the treated population

        4. Estimate median progression free survival (mPFS) of the treated population

        5. Estimate disease control rate (DCR) at 8 weeks

        6. Evaluate quality of life while receiving the combination therapy
    

Trial Arms

NameTypeDescriptionInterventions
Combination of lonsurf + gemcitabine + nab-paclitaxelExperimental
  • Lonsurf
  • Gemcitabine
  • Nab-Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          1. ≥ 18 years old at the time of informed consent

          2. Ability to provide written informed consent and HIPAA authorization

          3. Untreated locally advanced Pancreatic Ductal Adenocarcinoma (PDAC) as defined by
             National Comprehensive Cancer Network (NCCN) guidelines or, untreated metastatic PDAC
             (prior adjuvant therapy is permitted if it's been greater than 6 months since
             completion)

          4. Histologically or cytologically confirmed PDAC

          5. Confirmed PDAC that is measurable or evaluable per RECIST 1.1

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          7. Gastrointestinal symptoms (nausea, vomiting, and diarrhea) of Grade 1 or less

          8. Adequate organ function as defined by:

               1. Aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5 x upper
                  limits of normal (ULN)

               2. Total bilirubin level ≤ 1.5 x ULN

               3. Creatinine level < 1.0 x ULN or creatinine clearance > 60 mL/min/1.73 m2 for
                  patients with creatinine levels above or below the institutional normal (as
                  determined by Cockcroft-Gault equation). For patients with a Body Mass Index
                  (BMI) > 30 kg/m2, lean body weight should be used to calculate the glomerular
                  filtration rate (GFR).

               4. Hemoglobin (Hgb) ≥ 9 g/dl

               5. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

               6. Platelets ≥ 100 x 109/L

               7. Acceptable coagulation studies as demonstrated by prothrombin time (PT) and
                  partial thromboplastin time (PTT) within normal limits (+/-15%) unless they are
                  on anticoagulation therapy

          9. Life expectancy estimated at ≥ 3 months

         10. Women of childbearing potential definition (WOCBP) must have a negative serum or urine
             pregnancy test performed within 14 days prior to initiation of study treatment.

             Any woman (regardless of sexual orientation, having undergone a tubal ligation, or
             remaining celibate by choice) is classified as WOCBP if she meets the following
             criteria:

               1. Has not undergone a hysterectomy or bilateral oophorectomy; or

               2. Has not been naturally postmenopausal for at least 24 consecutive months (i.e.
                  has had menses at any time in the preceding 12 consecutive months).

         11. WOCBP and men must agree to use adequate contraception prior, to study entry, for the
             duration of study participation, and 8 weeks after the end of treatment.

        Exclusion Criteria:

          1. Prior FOLFIRINOX (a combination of the chemotherapy drugs fluorouracil [5-FU],
             leucovorin, irinotecan and oxaliplatin) in the neoadjuvant or adjuvant setting

          2. Neuropathy > Grade 1 at baseline

          3. Prior systemic chemotherapy for any other malignancy (aside from adjuvant therapy for
             PDAC) in the last 3 years

          4. Active malignancy other than PDAC

          5. Prior exposure to nab-paclitaxel, paclitaxel, or other taxanes

          6. History of bowel obstruction in the preceding 3 months of therapy, including gastric
             outlet obstruction related to PDAC

          7. Large, uncontrolled ascites requiring paracentesis

          8. Major surgery, other than diagnostic or laparoscopic surgery, within 4 weeks prior to
             first dose. (Port placement would not be considered a surgery.)

          9. Any brain metastases including leptomeningeal metastases

         10. Pregnant or breastfeeding

         11. Significant gastrointestinal disorder(s) that would, in the opinion of the Principal
             Investigator, prevent absorption of an orally available agent (e.g., Crohn's disease,
             ulcerative colitis, extensive gastric resection, and small intestinal resection)

         12. Uncontrolled chronic diarrhea > Grade 1 at baseline.

         13. Uncontrolled intercurrent illness including, but not limited to uncontrolled active
             infection, clinically significant non-healing or healing wounds, symptomatic
             congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia,
             significant pulmonary disease, uncontrolled infection, or psychiatric illness/social
             situations that would limit compliance with study requirements.

         14. Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung

         15. History of posterior reversible encephalopathy syndrome

         16. Enrollment on any additional investigational agent study

         17. Known hypersensitivity to gemcitabine or taxanes

         18. Patients with history of gemcitabine toxicity in the adjuvant setting requiring more
             than 1 dose level reduction

         19. Significant cardiac disease including the following: unstable angina, New York Heart
             Association class III-IV congestive heart failure, myocardial infarction < 6 months
             prior to study enrollment

         20. History of hemolytic-uremic syndrome

         21. Known infection with Human Immunodeficiency Virus (HIV) and/or active infection with
             hepatitis B or hepatitis C
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency of Dose Limiting Toxicities (DLTs)
Time Frame:28 days (Cycle 1)
Safety Issue:
Description:Number of DLTs observed

Secondary Outcome Measures

Measure:Frequency of adverse events in the safety evaluable population
Time Frame:from start of treatment until 30 days after treatment discontinuation (i.e up to 2 years)
Safety Issue:
Description:safety and toxicity data will be assessed using NCI CTCAE v5.0
Measure:Response rate to the combination of lonsurf, gemcitabine, and nab-paclitaxel in the efficacy evaluable population
Time Frame:from start of treatment until treatment discontinuation (i.e. up to 2 years)
Safety Issue:
Description:Using RECIST 1.1
Measure:Median Overall Survival (mOS) of the treated population
Time Frame:from start of treatment until death or last known follow up (i.e up to 2 years)
Safety Issue:
Description:
Measure:Median Progression-free Survival (mPFS) of the treated population
Time Frame:from start of treatment until disease progression or last follow up (i.e. up to 2 years)
Safety Issue:
Description:
Measure:Disease control rate (DCR)
Time Frame:8 weeks
Safety Issue:
Description:Disease control rate (DCR) as defined by (complete response + partial response + stable disease)
Measure:European Organization for Research and Treatment of Cancer quality of life questionnaire
Time Frame:Day 1 of each cycle(each cycle is 28 days),from start of treatment until disease progression or discontinuation of treatment (i.e. up to 2 years)
Safety Issue:
Description:Scale scores were calculated by averaging items within scales and transforming average scores linearly. All of the scales range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Patrick Joseph Loehrer Sr.

Trial Keywords

  • Pancreatic Ductal Adenocarcinoma
  • Pancreatic Cancer
  • Metastatic Pancreatic Cancer
  • Locally Advanced Pancreatic Cancer

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