J1320: A Phase 2, Randomized, Multicenter Study of PEGPH20 (PEGylated Recombinant Human Hyaluronidase) Combined with nab-Paclitaxel Plus Gemcitabine Compared with nab-Paclitaxel Plus Gemcitabine in Subjects with Stage IV Previously Untreated Pancreatic Cancer
Primary Objective: To estimate the progression-free survival (PFS) duration of PEGPH20 combined with NAB plus GEM (PAG treatment). Secondary Objective: 1. To estimate the relative benefit of PAG treatment versus NAB plus GEM (AG treatment), as assessed by the PFS hazard ratio. 2. To estimate the relative benefit of PAG treatment versus AG treatment, as assessed by the PFS hazard ratio based on subject tumor-associated HA levels. 3. To estimate the ORR, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), of PAG treatment and the relative benefit of PAG treatment versus AG treatment. 4. To estimate the OS duration of PAG treatment and the relative benefit of PAG treatment versus AG treatment, as assessed by the OS hazard ratio. 5. To evaluate the safety and tolerability profile of the PAG and AG treatment groups. 6. To characterize the plasma PK of PEGPH20 when given in combination with NAB plus GEM.
1. Signed, written Institutional Review Board (IRB)/Ethics Committee (EC)-approved Informed Consent Form (ICF). 2. Histologically confirmed Stage IV PDA with documented disseminated neoplasm to the liver and/or the lung. 3. One or more metastatic tumors measurable on computed tomography (CT) scan per RECIST v1.1, excluding the primary pancreatic lesion. 4. No previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease. Prior treatment for non-metastatic disease with 5-FU or GEM administered as radiation sensitizer, or as a cytotoxic therapy, in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no â?¥ Grade 2 treatment-related toxicities are present. 5. Karnofsky Performance Status â?¥70%. 6. Life expectancy â?¥3 months. 7. Age â?¥18 years. 8. A negative serum pregnancy test, if female of reproductive potential. 9. Screening clinical laboratory values as follows: â?? Total bilirubin â?¤1.5 times upper limit of normal (ULN). â?? Aspartate aminotransferase ([AST]; serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase ([ALT]; serum glutamic pyruvate transaminase [SGPT]) â?¤2.5 times ULN, (if liver metastases are present, then â?¤5 times ULN is allowed). â?? Serum creatinine â?¤2.0 mg/dL or calculated creatinine clearance â?¥60 mL/min. â?? Serum albumin â?¥3.0 g/dL. â?? Absolute neutrophil count (ANC) â?¥1,500 cells/mm3. â?? Platelet count â?¥100,000 plt/mm3. â?? Hemoglobin â?¥9 g/dL. â?? Prothrombin time (PT)/international normalized ratio (INR) within normal limits (Â±15%) or within therapeutic range if on warfarin. â?? Partial thromboplastin time (PTT) within normal limits (Â±15%). 10. For men and women of reproductive potential, agreement to use an effective contraceptive method from the time of screening and throughout their time on study. Effective contraceptive methods consist of prior sterilization, intra-uterine device, oral or injectable contraceptives, and/or barrier methods. Abstinence alone is not considered an adequate contraceptive measure for the purposes of this study. 11. Non-metastatic PDA. 12. Known central nervous system involvement or brain metastases. 13. New York Heart Association Class III or IV cardiac disease or myocardial infarction within the past 12 months. 14. Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy. 15. Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C. 16. Known allergy to hyaluronidase. 17. Women currently pregnant or breastfeeding. 18. Intolerant of dexamethasone. 19. History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer or curatively-treated cervical carcinoma in-situ. 20. Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or that may render the subject at high risk for treatment complications. 21. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the subject unsuitable for the study. 22. Inability to comply with study and follow-up procedures as judged by the Investigator.
This is a Phase 2, multicenter, open-label, randomized study with a run-in phase. The run-in phase will evaluate the safety and tolerability of PEGPH20+NAB+GEM (PAG treatment) and compare it with NAB+GEM (AG treatment) before initiating Phase 2. Phase 2 will be an open-label randomized study. The dosing schedule for subjects randomized to the PAG and AG treatment groups will be the same in the run-in phase and Phase 2 (see Section 6.1.3). The treatment period will consist of 4-week treatment cycles (28 days) with Week 4 of every cycle as a washout week (i.e., no treatment will be given). Treatment will continue until disease progression or unacceptable toxicity is documented. RUN IN PHASE: In the run-in phase, approximately 8 subjects will be randomized in a 3:1 ratio to receive PEGPH20 (3.0 Î¼g/kg) in combination with standard dosing of NAB+GEM (PAG treatment) or NAB+GEM (AG treatment). No stratification factors will be used. Additional subjects may be enrolled to further assess the tolerability of PEGPH20 in order to establish the acceptable safety profile prior to the randomization of the Phase 2 study. The Sponsor, the participating Investigators, and the independent safety physician will determine if the dose and regimen for Phase 2 is acceptable after reviewing all available safety data from Cycle 1 from all subjects in the run-in phase. PHASE II: In Phase 2, approximately 124 subjects will be randomized in a 1:1 ratio to receive PEGPH20 (3.0 Î¼g/kg, pending outcome of run-in phase safety assessment) in combination with standard dosing of NAB+GEM (PAG treatment) or NAB+GEM (AG treatment). Randomization will be stratified by Karnofsky Performance Status (70 to 80% and 90 to 100%).
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