E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced pancreatic cancer
The overall objective of this clinical study is to evaluate a potential synergy between gemcitabine and IMM-101 and any beneficial effect this may have on safety and tolerability, QoL, clinical signs and symptoms of disease, disease outcome and selected markers of tumour burden and immunological status in patients with inoperable, locally advanced or metastatic pancreatic cancer. |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033606 |
E.1.2 | Term | Pancreatic cancer non-resectable |
E.1.2 | System Organ Class | 100000004864 |
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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 |
No clinically relevant deleterious effect of IMM-101 on safety and tolerability profiles as judged by:
• Local and systemic toxicities.
• Number, type and degree of toxicities as measured by the NCI CTCAE v4.0.
• QoL (EORTC QLQ-C30 supplemented with EORTC QLQ-PAN26).
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E.2.2 | Secondary objectives of the trial |
A clinically relevant improvement in one or more markers of disease status and progression:
• Overall survival (OS).
• Progression-free survival (PFS).
• Overall response rate (ORR).
• Reduction in metastatic disease
• Circulating levels of carbohydrate antigen 19.9 (CA19.9).
• Circulating levels of carcinoembryonic antigen (CEA).
• Nutritional status (weight, appetite, serum albumin).
• Pain control and analgesic use.
Exploratory endpoints may include:
•A change in levels of circulating tumour cells consistent with a reduction or stabilisation of tumour burden.
•A change in one or more markers of immune status based on cellular involvement or cytokine/immune mediator production.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title:
A Long-Term Follow-Up Sub-Study of a Randomised, Open-Label, Proof-of-Concept, Phase II Trial of IMM-101 in Advanced Pancreatic Cance
Date: 18 May 2012 (Appendix 8 to Prootocol V3.0
Objectives:
To describe the long term safety profile of IMM-101 administered intradermally for extended use
To document the clinical course of the patients who previously completed the IMM-101-002 main study.
Exploratory endpoints:
Blood samples will be collected from all patients approximately every four weeks and sera prepared for analysis of selected tumour markers in addition to immunological markers and mediators such as, for example, cytokines and antibodies, or any other clinically or immunologically relevant assays that may become pertinent during the course of the clinical trial.
Eligibility:
Patients are eligible to be included in the study if they:
- Previously completed the IMM-101-002 main study
- Give signed informed consent for participation in this follow-up study
Patients will be ineligible if one or more of the following statements are applicable:
- Patient is unable or unwilling to comply with the protocol.
- Patient is not considered suitable by the investigator for the study.
- Female patient of child-bearing potential who is not using an approved method of birth control (e.g., physical barrier [patient and partner], contraceptive pill or patch, spermicide and barrier, intrauterine device [IUD] or abstinence). Those patients that utilise hormonal contraceptives must have used the same method for at least three months before additional barrier contraception is discontinued from being used concomitantly with the hormonal contraception. Patient of non-child-bearing potential are defined as having 12 month amenorrhoea or are surgically sterile.
- Female patient who is pregnant, breast feeding or planning a pregnancy during the course of the study. A pre-treatment urine pregnancy test measuring human chorionic gonadotrophin (hCG) must be negative.
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E.3 | Principal inclusion criteria |
Histologically and/or cytologically confirmed inoperable ductal adenocarcinoma of the pancreas, including the mucinous variant. This will include locally advanced and metastatic disease (stage III/IV).
Presence of measurable lesions in at least one site which have not been previously irradiated (bone lesions, ascites and pleural effusions are not considered as measurable), described as any of the following:
• Any primary tumour with at least bi-dimensionally measurable disease.
• a) Palpable lymph nodes, b) Deep seated lymph nodes.
• Liver metastases measurable by computerised tomography (CT) scan.
• Deep seated soft tissue lesions measurable by CT scan.
WHO performance status of 0-2.
Serum creatinine <140 µmol/L.
White blood cell (WBC) count, including differential counts within the normal range or, if outside the normal range, considered by the investigator to be not clinically significant.
Life expectancy, in the opinion of the Investigator, of >3 months from randomisation.
Provide written informed consent to participate as shown by a signature and date on the patient's informed consent form (ICF)
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E.4 | Principal exclusion criteria |
Patients will be ineligible if one or more of the following statements are applicable:
Patient has acinar cell carcinoma, neuroendocrine tumours, lymphomas or squamous cell carcinomas.
Patient has severe, active uncontrolled infection requiring systemic antibiotics, antiviral or antifungal treatments.
Patient has been on any previous chemotherapy treatment for pancreatic cancer.
Patient is eligible for resection of the pancreatic primary tumour but has either refused the operation or is considered to be medically unfit for the operation.
Patient has clinical or CT evidence of central nervous system (CNS) metastases.
Patient has any previous or concurrent malignancy, except adequately treated carcinoma in situ of the cervix, basal cell carcinoma of the skin and/or non-melanoma skin cancer, or if previous malignancy was more than 5 years prior and there are no signs of recurrence.
Patient has serum albumin < 26 g/L.
Patient has a C-reactive protein (CRP) > 70 mg/L.
Patient has had radiotherapy in the 6 weeks prior to screening.
Patient has used depot corticosteroids in the 6 weeks prior to screening.
Patient has had chronic use of any systemic corticosteroids (>10 mg per day of prednisolone or equivalent for a period of 2 weeks or more) and/or immunosuppressant drugs (such as azathioprine, tacrolimus, cyclosporin) within the 2-week period prior to the first administration of study drug.
Female patient of child-bearing potential who is not, in the opinion of the Investigator, using an approved method of birth control (e.g. physical barrier [patient and partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device [IUD]). Those patients that utilise hormonal contraceptives must have used the same method for at least three months before study dosing. Patient of non-child-bearing potential are defined as having 12 month amenorrhoea or are surgically sterile.
Female patient who is pregnant, breast feeding or planning a pregnancy during the course of the study. A pre-treatment serum pregnancy test measuring human chorionic gonadotrophin (HCG) must be negative.
Patient has been administered any investigational drug, vaccine or device in the 3 months prior to screening. Patient has a surgical or medical condition which, in the judgement of the Investigator, might interfere with the activity of IMM-101, or with the performance of this study.
Patient has presence of any uncontrolled concomitant disease (e.g. unstable angina pectoris, congestive heart failure, myocardial infarction, arrhythmias, uncontrolled severe hypertension) which, in the judgement of the Investigator, might interfere with the activity of IMM-101, or with the performance of this study.
Patient has a history of serious adverse reaction or serious hypersensitivity to any drug.
Patient has had any previous treatment with IMM-101 or related mycobacterial immunotherapy.
Patient is known to have a history of human immunodeficiency virus (HIV) or syphilis, current symptomatic Hepatitis B or C. Testing is not required in the absence of clinical signs and symptoms suggestive of infection with HIV.
Patient is unable or unwilling to comply with the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
No clinically relevant deleterious effect of IMM-101 on safety and tolerability profiles as judged by:
Local and systemic toxicities.
Number, type and degree of toxicities as measured by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v4.0.
QoL (EORTC QLQ-C30 questionnaire supplemented by the pancreas cancer specific EORTC QLQ-PAN26 questionnaire).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 6 months and 12 months treatment |
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E.5.2 | Secondary end point(s) |
A clinically relevant improvement in one or more markers of disease status and progression:
• Overall survival (OS).
• Progression-free survival (PFS).
• Overall response rate (ORR).
• Reduction in metastatic disease.
• Circulating levels of carbohydrate antigen 19.9 (CA19.9).
• Circulating levels of carcinoembryonic antigen (CEA).
• Nutritional status (weight, appetite, serum albumin).
• Pain control and analgesic use
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 6 months and 12 months treatment |
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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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
standard of care (Gemcitabine) |
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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 | 30 |
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 | 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
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |