A Trial Comparing Gemcitabine With and Without IMM-101 in Advanced Pancreatic Cancer
To compare, in patients with advanced pancreatic cancer, the effects of IMM-101 in combination with gemcitabine to gemcitabine alone on safety and tolerability (including QoL), clinical signs and symptoms of disease, selected markers of tumour burden and immunological status, and disease outcome.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomised, Open-Label, Proof-of-Concept, Phase II Trial Comparing Gemcitabine With and Without IMM-101 in Advanced Pancreatic Cancer|
- No clinically relevant deleterious effect of IMM-101 on safety and tolerability. [ Time Frame: After 12 months or as clinically indicated ] [ Designated as safety issue: Yes ]
A clinically relevant deleterious effect of IMM-101 on safety and tolerability profiles will be 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).Efficacy will be defined as a clinically relevant improvement in one or more markers of disease status.
- A clinically relevant improvement in one or more markers of disease status [ Time Frame: 12 months or as clinically indicated ] [ Designated as safety issue: No ]
A clinically relevant improvement in one or more markers of disease status:
- 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.
- Immunological markers [ Time Frame: 12 months or as clinically indicated ] [ Designated as safety issue: No ]
Blood samples will be collected from all patients for analysis of immunological markers and mediators (e.g. cytokines and antibodies, any other immunologically relevant assays.
For a subset of patients cells will be isolated from the whole blood samples. Exploratory endpoints may include:
- A change in levels of circulating tumour cells (CTCs)
- A change in one or more markers of immune status
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||August 2014|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Active Comparator: gemcitabine chemotherapy
Patients in the control arm will receive normal standard of care - up to 12 cycles of Gemcitabine. Dosing of Gemcitabine is as per the normal orescribing information for pancreatic cancer.
Gemcitabine will be administered intravenously at 1000 mg/m2 over 30 minutes once weekly for 3 consecutive weeks out of every 4 weeks.
Chemotherapy will be offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles (i.e. approximately 48 weeks).
Dosage reduction with each cycle or within each cycle may be applied based upon the grade of Gemcitabine-related toxicity experienced by the patient using centre's standard protocol.
Other Name: Gemzar
Experimental: IMM-101 in addition to gemcitabine
Patients in the experiemental arm will recieve IMM-101 in addition the current standard of care, namely chemotherapy (Gemcitabine). The treatment regimen with IMM-101 will be every 2 weeks for the first 3 doses followed by a rest of 4 weeks then every 2 weeks for the next 3 doses followed by every 4 weeks thereafter.
For patients in the active group, chemotherapy (GEM) will begin at least 14 days after first dose of IMM-101.
Chemotherapy plus IMM-101 will be offered until intolerable toxcity or withdrawal from the study up to a maximum of 12 cycles (i.e. approximately 48 weeks).
IMM-101 is a suspension of heat-killed whole cell M. obuense in borate-buffered saline.
A single 0.1 mL intradermal injection of IMM-101 (10 mg/mL)will be administered every 2 weeks for the first 3 doses followed by a rest of 4 weeks then every 2 weeks for the next 3 doses followed by every 4 weeks thereafter.
Chemotherapy plus IMM-101 will be offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles of gemcitabine.
Other Name: Heat killed whole cell Mycobacterium obuense, M. obuense
|Cyprus Oncology Centre|
|Nicosia, Strovolos, Cyprus, 2006|
|Adelaide, Meath & National Childrens Hospital,|
|Dublin, Ireland, Dublin 24|
|St Vicents University Hospital|
|Dublin, Ireland, Dublin 4|
|A.O. Santa Croce e Carle, Struttura Complessa di Oncologia Medica|
|Confreria, Cuneo, Italy|
|Azienda Ospedaliero-Universitaria di Bologna|
|Bologna, Italy, 40138|
|Azienda Ospedaliera San Gerardo Struttura Complessa Oncologia Medica|
|Monza, Italy, 20052|
|AOU Maggiore della Carità|
|Medical Oncology Department, Central University Hospital of Asturias|
|Asturias, Oviedo, Spain|
|Hospital General de Alicante|
|Alicante, Spain, 03010|
|Hospital Gregorio Marañon|
|Madrid, Spain, 28007|
|Instituto Valenciano de Oncologia|
|Valencia, Spain, 46009|
|Department of Medical Oncology, Hospital Universitari La Fe,|
|Hospital Miguel Servet|
|Zaragoza, Spain, 50009|
|Airedale General Hospital|
|Skipton, West Yorkshire, United Kingdom, BD20 6TD|
|Royal Blackburn Hospital|
|Blackburn, United Kingdom, BB2 3HH|
|Bradford Royal Infirmary|
|Bradford, United Kingdom, BD9 6RJ|
|Velindre Cancer Centre|
|Cardiff, United Kingdom, Velindre Cancer Centre|
|Dundee, United Kingdom, DD1 9SY|
|The London Clinic Cancer Centre|
|London, United Kingdom, W1G 6BW|
|Mount Vernon Cancer Centre|
|London, United Kingdom, HA6 2RN|
|Peterbrough City Hospital, Haematology/Oncology Dept,|
|Peterborough, United Kingdom, PE3 9GZ|
|Principal Investigator:||Angus Dalgleish, Professor||St George's, University of London|