Clinical Trials /

Evaluation of Efficacy and Safety of Neoadjuvant Treatment With Pamrevlumab in Combination With Chemotherapy (Gemcitabine and Nab-paclitaxel) in Locally Advanced Pancreatic Cancer

NCT03941093

Description:

This is a Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of neoadjuvant treatment with pamrevlumab or placebo in combination with gemcitabine plus nab-paclitaxel (G/NP) in the treatment of locally advanced, unresectable pancreatic cancer subjects.

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of Efficacy and Safety of Neoadjuvant Treatment With Pamrevlumab in Combination With Chemotherapy (Gemcitabine and Nab-paclitaxel) in Locally Advanced Pancreatic Cancer
  • Official Title: A Phase 3, Randomized, Double-Blind Study of Pamrevlumab or Placebo in Combination With Gemcitabine Plus Nab-paclitaxel (G/NP) as Neoadjuvant Treatment in Patients With Locally Advanced, Unresectable Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: FGCL-3019-087
  • NCT ID: NCT03941093

Conditions

  • Pancreatic Cancer Non-resectable

Interventions

DrugSynonymsArms
Pamrevlumab + Gemcitabine + Nab-paclitaxelFG-3019, Gemzar, AbraxaneArm A
Placebo + Gemcitabine + Nab-paclitaxelGemzar, AbraxaneArm B

Purpose

This is a Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of neoadjuvant treatment with pamrevlumab or placebo in combination with gemcitabine plus nab-paclitaxel (G/NP) in the treatment of locally advanced, unresectable pancreatic cancer subjects.

Detailed Description

      Subjects will be randomized in a 1:1 ratio to one of the two study treatment arms;
      pamrevlumab with G/NP or placebo with G/NP.

      Each subject may receive up to six cycles of treatment (each treatment cycle is 28 days).
      Tumor tissue will be collected during resection to determine surgical outcome and for
      biomarker analysis. Tumor response will be evaluated by changes in CT scan, FDG-PET, CA 19-9,
      and NCCN® guidelines.

      All subjects randomized will have a safety follow-up visit approximately 28 days after the
      last dose of study treatment.

      Subjects who complete 6 cycles of treatment will be evaluated for surgical exploration for
      possible R0 or R1 resection. Surgery will occur at least 4 weeks after the last dose
      (allowing for a wash-out period from treatment) and only after receipt of the recommendation
      from the central review board with regards to surgical eligibility. Surgery will occur no
      longer than 8 weeks after the last dose. Subjects who undergo surgery will be evaluated for
      surgical complications for at least an additional 30 days following discharge from surgery.

      Subjects who are ineligible for surgical exploration (i.e. subjects who did not complete 6
      cycles of treatment or do not meet any of the protocol defined criteria or had a
      contraindication to surgery) will continue in the Follow-up period and receive treatment as
      per standard of care (SOC) for each institution.

      All subjects will be followed for disease progression (if not previously detected) or
      recurrence following resection (local progression or metastatic disease). Subjects will also
      be followed for any additional anti-cancer therapy received for their pancreatic cancer. All
      subjects will be followed for survival (until death) or until the last subject to complete
      treatment reaches 18 months post-treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalPamrevlumab + Gemcitabine + Nab-paclitaxel
  • Pamrevlumab + Gemcitabine + Nab-paclitaxel
Arm BPlacebo ComparatorPlacebo + Gemcitabine + Nab-paclitaxel
  • Placebo + Gemcitabine + Nab-paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          1. Understand and sign informed consent; be willing to comply with study procedures,
             including surgery

          2. Age ≥ 18 years

          3. Be a male, or non-pregnant and non-lactating female

          4. Negative serum B-hCG pregnancy test at screening for women of childbearing potential

          5. Male subjects with partners of childbearing potential and female subjects of
             childbearing potential are required to use double barrier contraception methods during
             the conduct of the study and for 3 months after the last dose of study drug

          6. Histologically proven diagnosis of pancreatic ductal adenocarcinoma (PDAC)

          7. Locally advanced pancreatic cancer considered unresectable according to NCCN
             Guidelines® Version 2.2018 as determined by central imaging

          8. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST
             1.1 criteria as determined by central imaging

          9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

         10. Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase
             (ALT) <2.5 x upper limit of normal (ULN), alkaline phosphatase <2.5 x ULN, and
             bilirubin ≤1.5 x ULN

         11. Adequate bone marrow function: platelets >100,000 cells/mm3, hemoglobin >9.0 g/dl and
             absolute neutrophil count (ANC) >1,500 cells/mm3

         12. Adequate renal function: creatinine < 1.5 x ULN, creatinine clearance ≥ 30 mL/min

         13. Less than grade 2 pre-existing peripheral neuropathy (per CTCAE)

        Exclusion Criteria:

          1. Prior chemotherapy or radiation for pancreatic cancer

          2. Previous (within the past 3 years) or concurrent malignancy diagnosis except
             non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer)

          3. Major surgery within 4 weeks prior to signing informed consent form. Biliary stents
             are permitted.

          4. History of allergy or hypersensitivity to human, humanized or chimeric monoclonal
             antibodies

          5. Any medical or surgical condition that may place the subject at increased risk while
             on study

          6. Any condition potentially decreasing compliance to study procedures

          7. Exposure to another investigational drug within 28 days of first dosing visit, or 5
             half-lives of the investigational drug (whichever is longer)

          8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             systemic infections, symptomatic congestive heart failure, unstable angina pectoris,
             clinically significant cardiac arrhythmia, or psychiatric illness/social situations
             that would limit compliance with study requirements

          9. Documented history of drug or alcohol abuse within 6 months of signing informed
             consent

         10. Any medical condition that, in the opinion of the investigator, may pose a safety risk
             to a subject in this trial, may confound the assessment of safety and efficacy, or may
             interfere with study participation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Randomization to death due to any cause or until the last subject to complete treatment reaches 18 months post-treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:Randomization until the last subject to complete treatment reaches 18 months post-treatment.
Safety Issue:
Description:
Measure:European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30 Version 3.0).
Time Frame:Baseline through safety follow up (~4 weeks post-last dose)
Safety Issue:
Description:The EORTC QLQ-C30 uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome. The EORTC QLQ-C30 uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 ("very poor") to 7 ("excellent"). Half points are not allowed. The range is 6. First of all, raw score has to be calculated with mean values. Afterwards linear transformation is performed to be comparable. More points are considered to have a better outcome
Measure:Patient-Reported Outcomes National Cancer Institute Common Terminology Criteria for Adverse Events (PRO CTCAE) Severity and Interference Items (decreased appetite, nausea, vomiting, diarrhea, abdominal pain and fatigue)
Time Frame:Time Frame: Days 1, 8 and 15 of the first three treatment cycles (Cycles 1-3) and Days 1 and 15 in the last three treatment cycles (Cycles 4-6), to be administered prior to dosing
Safety Issue:
Description:6 item questionnaire with 1-3 questions per item related to frequency, severity and interference Frequency answers range from Never to Almost Constantly Severity answers range from None to Very Severe Interference answers range from Not at all to Very much. PRO-CTCAE responses are scored from 0 to 4, and there are no standardized scoring rules yet established for how to combine attributes into a single score or how best to analyse PRO-CTCAE data longitudinally. PRO-CTCAE scores for each attribute (frequency, severity and/or interference) will be presented descriptively

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:FibroGen

Trial Keywords

  • locally advanced pancreatic cancer
  • unresectable pancreatic cancer

Last Updated