A Phase 3, Multicenter, Open-Label, Randomized Study of nab(RegisteredTM)-Paclitaxel Plus Gemcitabine Versus Gemcitabine Alone as Adjuvant Therapy in Subjects with Surgically Resected Pancreatic Adenocarcinoma
- Zale Lipshy University Hospital
This is a Phase 3, international, multicenter, randomized, open-label, controlled study to assess the efficacy of nab-paclitaxel in combination with gemcitabine (arm a) compared with gemcitabine alone (arm B) as adjuvant treatment for 6 cycles. Subjects will be assigned to treatments by a stratified randomization with 1:1 ratio.
The stratification factors will include:
* Resection Status: R0 (tumor-free margin) versus R1 (microscopically positive margin)
* nodal Status: lymph node (Ln)+ versus Ln-
* Region (north america, europe, and australia versus asia Pacific, versus other)
arm a will receive nab-paclitaxel 125 mg/m2 administered iV followed by gemcitabine 1000 mg/m2 given intravenously (iV) weekly on Days 1, 8, and 15 of a 28-day cycle for a total of 6 cycles.
arm B will receive gemcitabine 1000 mg/m2 administered iV weekly on Days 1, 8, and 15 of a 28-day cycle for a total of 6 cycles.
Dose interruptions, and up to 2 dose reductions to 100 mg/m2 and 75 mg/m2 for nab-paclitaxel and 800 mg/m2 and 600 mg/m2 for gemcitabine, are allowed.
Primary endpoint-The primary endpoint of the study is independently assessed DFS, which is defined as the time
from the date of randomization to the date of disease recurrence or death, whichever is earlier.
Secondary endpoint(s)- The secondary endpoints of the study are:
- oS, which is defined as the time from the date of randomization to the date of death
- The incidence of Teaes, Saes, laboratory abnormalities and other safety parameters
exploratory endpoint(s)-The exploratory endpoints of the study are:
- Molecular profiling of tumor
- identification of tumor nucleic acids from blood
- Differences in outcomes between the european organization for Research and
Treatment of Cancer (eoRTC) quality of life questionnaires (QLQ), eoRTC QLQC30
and QLQ-Pan26, during and after treatment versus at baseline
1. Histologically confirmed resected ductal pancreatic adenocarcinoma with macroscopic complete resection (R0 and R1). Subjects with neuroendocrine (and mixed type) tumors are excluded.
2. Pancreatic cancer staging: T 1-3, N0-1, M0.
3. Subject should be able to start treatment no later than 12 weeks postsurgery.
4. Male or non-pregnat, non-lactating females who are >=18 years of age at the time of signing the informed consent form (ICF).
5. ECOG performance status of 0 or 1.
6. Acceptable hematology parameters:
* Absolute neutrophil count >=1500 cell/mm3
* Platelet count >=100,000/mm3
* Hemoglobin (Hgb) >=9 g/dL
7. Acceptable blood chemistry levels:
* AST/ SGOT and ALT/ SGPT <=2.5 x upper limit of normal range (ULN)
* Total bilirubin <= ULN (subjects with Gilbert[Single Quote]s syndrome can have bilirubin of up to 1.5 x ULN)
* Alkaline phosphatase <= 2.5 x ULN
* Serum creatinine within upper limits of normal or calculated clearance >=50 mL/min/1.73 m2. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (eg, using the Cockroft-Gault formula). For subjects with a Body Mass Index (BMI) >30 kg/m2, lean body weight should be used instead
8. CA19-9 <100 U/mL assessed within 14 days of randomization
9. Acceptable coagulation studies (eg. PT or INR, and PTT within normal limits ((+ or -)15%)
10. Females of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [ie, has had menses at any time during the preceding 24 consecutive months]) must:
* Agree to the use of two physician-approved contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study IP for 3 months following the last dose of IP
* Has negative serum pregnancy test ([BETA] -hCG) result at screening
11. Male subjects:
a. Must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following IP discontinuation, even if he has undergone a successful vasectomy. [True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.]
12. Understand and voluntarily sign an ICF prior to any study related assessments or procedures being conducted.
13. Be able to adhere to the study visit schedule and other protocol requirements.