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

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ClinicalTrials.gov Identifier: NCT03941093
Recruitment Status : Not yet recruiting
First Posted : May 7, 2019
Last Update Posted : May 14, 2019
Sponsor:
Information provided by (Responsible Party):
FibroGen

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Non-resectable Drug: Pamrevlumab + Gemcitabine + Nab-paclitaxel Drug: Placebo + Gemcitabine + Nab-paclitaxel Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 256 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind
Primary Purpose: Treatment
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
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Experimental: Arm A
Pamrevlumab + Gemcitabine + Nab-paclitaxel
Drug: Pamrevlumab + Gemcitabine + Nab-paclitaxel

Drug: Pamrevlumab is administered on Days 1, 8 and 15 of Treatment Cycle 1 and on Day 1 and 15 of each subsequent treatment cycle via IV infusion. The dose level is 35 mg/kg.

Drug: Gemcitabine is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion. The dose level is 1000 mg/m2.

Drug: Nab-paclitaxel is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion. The dose level is 125 mg/m2.

Other Names:
  • FG-3019
  • Gemzar
  • Abraxane

Placebo Comparator: Arm B
Placebo + Gemcitabine + Nab-paclitaxel
Drug: Placebo + Gemcitabine + Nab-paclitaxel

Drug: Placebo is administered on Days 1, 8 and 15 of Treatment Cycle 1 and on Day 1 and 15 of each subsequent treatment cycle via IV infusion.

Drug: Gemcitabine is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion. The dose level is 1000 mg/m2.

Drug: Nab-paclitaxel is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion. The dose level is 125 mg/m2.

Other Names:
  • Gemzar
  • Abraxane




Primary Outcome Measures :
  1. 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 ]
  2. Proportion of all randomized subjects in whom R0 or R1 resection is achieved [ Time Frame: After completion of 24 weeks of treatment ]

Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Randomization until the last subject to complete treatment reaches 18 months post-treatment. ]
  2. 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) ]

    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


  3. 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 ]

    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03941093


Contacts
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Contact: Raquel Ortega 415-978-1562 rortega@Fibrogen.com

Sponsors and Collaborators
FibroGen

Additional Information:
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Responsible Party: FibroGen
ClinicalTrials.gov Identifier: NCT03941093     History of Changes
Other Study ID Numbers: FGCL-3019-087
First Posted: May 7, 2019    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by FibroGen:
locally advanced pancreatic cancer
unresectable pancreatic cancer

Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Digestive System Diseases
Endocrine System Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Gemcitabine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs