| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Adenocarcinoma of the Pancreas |
|
| E.1.1.1 | Medical condition in easily understood language |
| Pancreatic cancer that has spread to other organs |
|
| 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 | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033599 |
| E.1.2 | Term | Pancreatic adenocarcinoma metastatic |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To evaluate the efficacy of the combination of ABI-007 and gemcitabine
versus gemcitabine alone in improving overall survival in patients with
metastatic adenocarcinoma of the pancreas. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the objective tumor response according to RECIST guidelines.
To evaluate progression-free survival according to RECIST guidelines.
To evaluate the safety and tolerability of this combination in this patient population. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient has definitive histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. The definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by integrating the histopathological data within the context of the clinical and radiographic data. Patients with islet cell neoplasms are excluded.
2. Initial diagnosis of metastatic disease must have occurred ≤6 weeks prior to randomization in the study.
3. Patient has one or more metastatic tumors measurable by CT scan (or MRI, if patient is allergic to CT contrast media).
4. Male or non-pregnant and non-lactating female, and ≥18 years of age.
• If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test (β-human Chorionic Gonadotropin (β-hCG) documented 72 hours prior to the first administration of study drug.
• If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator during the period of administration of study drug. In addition, male and female patients must utilize contraception after the end of treatment as recommended in the product's Summary of Product Characteristics or
Prescribing Information provided in the study manual.
5. Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Patients having received cytotoxic doses of
gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study.
6. Patient has adequate biological parameters as demonstrated by the following blood counts at Baseline (obtained ≤14 days prior to randomization):
• Absolute neutrophil count (ANC) ≥1.5 × 10^9/L;
• Platelet count ≥100,000/mm3 (100 × 10^9/L);
• Hemoglobin (Hgb) ≥9 g/dL.
7. Patient has the following blood chemistry levels at Baseline (obtained ≤14 days prior to randomization):
• AST (SGOT), ALT (SGPT) ≤2.5 × upper limit of normal range (ULN), unless liver metastases are clearly present, then ≤5 × ULN is allowed
• Total bilirubin ≤ULN
• Serum creatinine within normal limits or calculated clearance ≥60 mL/min/1.73 m² for patients with serum creatinine levels above or below the institutional normal value. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (eg, using the Cockroft-Gault formula). For patients with a Body Mass Index (BMI) >30 kg/m², lean body weight should be used instead.
8. Patient has acceptable coagulation studies (obtained ≤14 days prior to randomization) as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (±15%).
9. Patient has no clinically significant abnormalities in urinalysis results (obtained ≤14 days prior to randomization).
10. Patient has a Karnofsky performance status (KPS) ≥ 70. Two observers will be required to assess KPS. If discrepant, the one with the lowest assessment will be considered true.
11. Patients should be asymptomatic for jaundice prior to Day 1. Significant or symptomatic amounts of ascites should be drained prior to Day 1. Pain symptoms should be stable and should not require modifications in analgesic management prior to Day 1.
12. Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities. |
|
| E.4 | Principal exclusion criteria |
1. Patient has known brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart).
2. Patient has only locally advanced disease.
3. Patient has experienced a ≥10% decrease in KPS between Baseline visit and within 72 hours prior to randomization.
4. Patient has a ≥20% decrease in serum albumin level between Baseline visit and within 72 hours prior to randomization.
5. History of malignancy in the last 5 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years.
6. Patient uses Coumadin.
7. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
8. Patient has known historical or active infection with HIV, hepatitis B, or hepatitis C.
9. Patient has undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
10. Patient has a history of allergy or hypersensitivity to any of the study drugs or any of their excipients, or the patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of the product or comparator SmPC or Prescribing Information.
11. History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).
12. Patients with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
13. History of chronic leukemias (eg, chronic lymphocytic leukemia).
14. Patients with high cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year.
15. History of Peripheral Artery Disease (eg, claudication, Leo Buerger's disease).
16. Patient has serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the patient's safety or the study data integrity.
17. Patient is enrolled in any other clinical protocol or investigational trial.
18. Patient is unwilling or unable to comply with study procedures, or is planning to take vacation for 7 or more consecutive days during the course of the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| overall survival of patients treated with ABI-007 in combination with gemcitabine compared to patients treated with gemcitabine alone |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| final analysis of survival will be conducted when at least 608 deaths have occurred |
|
| E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are:
• Progression-free survival according to RECIST guidelines.
• Objective tumor response based on computed tomography (CT) scans (or magnetic resonance imaging (MRI) scans, if patient is allergic to contrast agent or has some other contraindication to a CT scan). These will be evaluated according to the RECIST guidelines. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| secondary efficacy endpoint will be evaluated only if the primary efficacy endpoint demonstrates superiority for ABI-007+gemcitabine over gemcitabine alone |
|
| 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 | Yes |
| 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 | Yes |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 38 |
| 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 |
| Austria |
| Belgium |
| Canada |
| France |
| Germany |
| Italy |
| Russian Federation |
| Spain |
| Ukraine |
| United States |
|
| 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 the point at which all patients in the trial have either completed the 18 months of survival follow-up or have died |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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