| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| LOCALLY ADVANCED OR METASTATIC PANCREATIC CANCER |
| Lokalt fremskreden eller spredt bugspytkirtelkræft |
|
| E.1.1.1 | Medical condition in easily understood language |
| Unresectable pancreas cancer |
| Lokalt fremskreden eller spredt bugspytkirtelkræft |
|
| 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 | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10033609 |
| E.1.2 | Term | Pancreatic carcinoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 overall survival at 6 months of gemcitabine/nab-paclitaxel plus tocilizumab and gemcitabine/nab-paclitaxel.
|
|
| E.2.2 | Secondary objectives of the trial |
1. To compare the efficacy, safety and quality of life of gemcitabine/nab-paclitaxel plus tocilizumab and gemcitabine/nab-paclitaxel.
2. To investigate whether circulating tumor KRAS mutations in in plasma are associated with disease outcome.
3. To assess whether IL-6 in plasma is correlated with clinical outcome and tocilizumab efficacy.
4. To assess whether inhibition of IL-6R has an impact on cachexia in patients with locally advanced or metastatic pancreatic cancer. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Signed informed consent
• Histological or cytological pancreatic adenocarcinoma. Malignant unspecified tumor cells in cytological specimen are allowed after investigator assessment, mixed histology including adenosquamous carcinoma is allowed
• Male or non-pregnant, non-lactating females who are ≥18 years of age at the time of signing the informed consent form (ICF)
• Non-curable unresectable locally advanced or metastatic pancreatic carcinoma
• A modified Glasgow Prognostic Score (mGPS) criteria of 1 or 2 assessed within 14 days of randomization as defined below:
• mGPS of 1: CRP > 10 mg/L and albumin ≥ 35 g/L
• mGPS of 2: CRP > 10 mg/L and albumin < 35 g/L
• No prior antineoplastic chemotherapy or anti-cancer drugs. Patients who have received neoadjuvant or adjuvant chemotherapy and who are diagnosed with loco regional recurrent or metastatic disease are not eligible
• ECOG/WHO Performance Status (PS) 0-1
• ≥ 4 weeks since prior major surgery, ≥ 2 weeks since prior minor surgery and ≥ 1 week since prior radiation therapy
• Measurable disease using the RECIST1.1 criteria, defined as lesions that can be measured in at least one dimension and which have not been previously irradiated. Longest diameter ≥ 20 mm with conventional techniques or ≥ 10 mm with spiral CT scan or MRI
• Fertile women of childbearing 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 use physician approved. i.e. highly effective, contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; or vasectomized partner) while on study IP; and for 3months following the last dose of chemotherapy; and has negative serum pregnancy test (β -hCG) result at screening
• Male subjects: must practice true abstinence (True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. (Periodicabstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception) or agree to use a condom during sexual contact with apregnant female or a female of childbearing potential while participating in the study,during dose interruptions and for 6 months following IP discontinuation, even if hehas undergone a successful vasectomy.
• Acceptable hematology parameters defined as:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
• Platelet count ≥ 100 x 10⁹/L
• Haemoglobin ≥ 5.6 mmol/L
• Acceptable liver function defined as:
• Serum bilirubin < 1.5 x upper limit of normal (ULN)
• ASAT/ALAT < 2.5 x ULN ( < 5 x ULN with known liver metastasis)
• Acceptable renal function with a creatinine clearance ≥ 50 mL/min/ (eg, using the Cockroft-Gault formula)
• Subjects must have signed and dated a BIOPAC IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care |
|
| E.4 | Principal exclusion criteria |
• Electrocardiogram (ECG) with significant modifications suggesting a high risk of occurrence of angina pectoris or high risk of arrhythmia.
• Other malignancies, except adequately treated basal carcinoma or squamous cell carcinoma of the skin or in-situ cervix carcinoma or incidental prostate cancer (T1a, Gleason score ≤ 6, PSA < 0.5 ng/ml), or any other tumor with a disease free survival of ≥ 5 years.
• History of serious or concurrent illness or uncontrolled medical disorder; any medical condition that might be aggravated by chemotherapy treatment or which could not be controlled; including, but not restricted to:
• Active infection requiring antibiotics within 2 weeks before the study inclusion
• Concurrent congestive heart failure NYHA ( class III - IV )
• Unstable angina pectoris, or myocardial infarction within 6 months and/or prior poorly controlled hypertension
• Inflammatory bowel disease (colitis, Crohns) or other serious gastrointestinal conditions associated with risk of perforation
• Peripheral neuropathy grade ≥ 2 according to CTCAE v 4.0
• Concomitant use of immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications.
• No known or suspected allergy to the investigational agents or any agents given in association with this trial.
• Pregnant or lactating women.
• Any psychological, familial, sociological, or geographical condition which does not permit protocol compliance and medical follow-up.
• Enrollment in any other clinical protocol or investigational study with an interventional agent or assessments that may interfere with study procedures. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall survival at 6 months. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Time Frame: Approximately up to 6 months. |
|
| E.5.2 | Secondary end point(s) |
1) Performance status at 3 and 6 months, assessed by both investigator and patient
2) Progression free survival (PFS), defined as the time from the date of randomization until the earliest date of disease progression determined by investigator assessment of objective radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or death due to any cause if sooner. [Time Frame: Randomization to disease progression, or death due to any cause if sooner. Approximately up to 6 months.]
3) Overall survival (OS), defined as the time from the date of randomization until death due to any cause. [Time Frame: Randomization until death due to any cause. Approximately up to 12 months.]
4) Overall response rate (ORR) (ORR = CR + PR). Objective response rate determined by radiographic disease assessments per RECIST 1.1, by investigator assessment. [Time Frame: Baseline through end of study. Approximately up to 6 months.]
5) Disease control rate (DCR), (DCR = CR + PR + SD), according to RECIST 1.1.
6) Safety (Data on safety parameters) Safety and tolerability of the treatment regimens assessed by a summary of adverse events and clinical laboratory assessments. [Time Frame: Baseline through approximately 30 days post treatment discontinuation. Approximately up to 6 months.]
7) Quality of Life (Quality of Life Questionnaire C30 (QLQ-C30) Version 3.0).
Exploratory
1) Identification of circulating tumor KRAS mutations in plasma
2) Assessing of plasma IL-6
3) Measure effects on body composition and plasma markers of inflammation/cachexia, and compare with tumor response, quality of life, and survival |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Time Frame: Approximately up to 6 months. |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 2 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| 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 | 4 |
Print
