| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Subjects With Surgically Resected Pancreatic Adenocarcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Subjects with pancreatic cancer who have recently undergone surgery to remove some of the affected tissue |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033602 |
| E.1.2 | Term | Pancreatic adenocarcinoma resectable |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare disease-free survival (DFS) between subjects randomized to nabpaclitaxel in combination with gemcitabine and subjects randomized to gemcitabine alone |
|
| E.2.2 | Secondary objectives of the trial |
-To assess overall survival (OS) between subjects randomized to nab-paclitaxel in combination with gemcitabine and subjects randomized to gemcitabine alone
- To assess safety and tolerability of the 2 treatment regimens |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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-pregnant, 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 × upper limit of normal range (ULN)
- Total bilirubin ≤ ULN (subjects with Gilbert’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. PTor INR and PTT within normal limits
(±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; and for 3 months following the last dose of IP; and
- Has negative serum pregnancy test (β -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.
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.
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception). |
|
| E.4 | Principal exclusion criteria |
The presence of any of the following will exclude a subject from enrollment:
1. Prior neo-adjuvant treatment, radiation therapy, or systemic therapy for pancreatic adenocarcinoma
2. Presence of or history ofmetastatic or locally recurrent pancreatic adenocarcinoma
3. Any other malignancy within 5 years prior to randomization, with the exception of
adequately treated in-situ carcinoma of the cervix, uteri, or nonmelanomatous skin cancer
(all treatment of which should have been completed 6 months prior to randomization)
4. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy,
defined as ongoing signs/symptoms related to the infection without improvement despite
appropriate antibiotics, antiviral therapy, and/or other treatment
5. Known history of human immunodeficiency virus (HIV) infection, or known history of active hepatitis B or C and are currently serologically positive with evidence of prior or signs of active chronic hepatitis
6. History of allergy or hypersensitivity to nab-paclitaxel or gemcitabine or any of their
excipients
7. Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the subject's safety or the study data integrity. These include, but are not limited to:
a. History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa)
b. History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies
c. History of the following within 6 months prior to Cycle 1 Day 1: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or ECG abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder
d. Peripheral neuropathy > grade 2
e. Concomitant use of immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications
8. Enrollment in any other clinical protocol or investigational study with an interventional agent or assessments that may interfere with study procedures
9. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
10. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
11. Any condition that confounds the ability to interpret data from the study
12. Unwillingness or inability to comply with study procedures |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint will be DFS, determined by an independent radiologist(s) who is blinded to the treatment assignment, which is defined as the time from the date of randomization to the date of disease recurrence or death, whichever is earlier. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Disease recurrence will be determined by the independent radiological
review of CT or MRI scans. Subjects who received new anti-cancer
therapy or cancer-related surgery prior to disease recurrence or death
will be censored. Detailed censoring rules will be documented in the
SAP.
The survival distribution of DFS will be estimated using the Kaplan-Meier
method |
|
| E.5.2 | Secondary end point(s) |
| The secondary efficacy endpoint will be OS which is defined as the time from the date of randomization to the date of death. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Subjects who are alive will be censored on the last-known-to be- alive date.
The survival distribution of OS will be estimated using the Kaplan-Meier method |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 82 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| Hong Kong |
| Korea, Republic of |
| New Zealand |
| Singapore |
| Taiwan |
| United States |
| Austria |
| Belgium |
| Denmark |
| Finland |
| France |
| Germany |
| Hungary |
| Ireland |
| Italy |
| Portugal |
| Spain |
| Sweden |
| United Kingdom |
| Czechia |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The End of Trial is defined as either the date of the last visit of the last subject to complete the study, or the date of receipt of the last data point from the last subject that is required for primary, secondary, and/or exploratory analysis, as pre-specified in the protocol. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
