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
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.
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.
18 Years and up
Accepting Healthy Volunteers?
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)
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