Clinical trial NCT01303172: A Trial Comparing Gemcitabine With and Without IMM-101 in Advanced Pancreatic Cancer
Official title: A Randomised, Open-Label, Proof-of-Concept, Phase II Trial Comparing Gemcitabine With and Without IMM-101 in Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Pancreatic Cancer
Lead sponsor: Immodulon Therapeutics Ltd
Sponsor class: INDUSTRY
First posted: 2011-02-24
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Patients in the IMM 101 treated group received an initial dose of IMM-101 followed by a maximum of 12 cycles of Gemcitabine (plus IMM-101); patients in the control group received Gemcitabine alone. All patients were to receive Gemcitabine once weekly for 3 consecutive weeks out of every 4 weeks. Patients in the IMM 101 treated group were to receive IMM 101 every 2 weeks for the first 3 doses, followed by a 4 week rest, then IMM-101 every 2 weeks for the next 3 doses. After this time, patients received doses every 4 weeks. Gemcitabine treatment began at least 14 days after the first dose of IMM-101 in the IMM 101 treated group.

Patients who completed the Main Study and who provided informed consent were eligible to participate in a long term treatment Sub-Study. All patients received IMM-101 in the open-label, single arm, Sub-Study irrespective of whether they had been randomised to Gemcitabine or Gemcitabine plus IMM-101 in the main study.

Eligibility criteria: Inclusion Criteria:

* Male or female; aged ≥18 years.
* 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.
* World Health Organization (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 not to be clinically significant.
* Life expectancy of \>3 months from randomisation.
* Provided written informed consent to participate as shown by a signature and date on the patient's Informed Consent Form

Exclusion Criteria:

* Acinar cell carcinoma, neuroendocrine tumours, lymphomas or squamous cell carcinomas.
* Severe, active uncontrolled infection requiring systemic antibiotics, antiviral or antifungal treatments.
* Any previous chemotherapy treatment for pancreatic cancer.
* Eligible for resection of the pancreatic primary tumour but has either refused the operation or is considered to be medically unfit for the operation.
* Clinical or CT evidence of central nervous system (CNS) metastases.
* 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 earlier and there were no signs of recurrence.
* Any previous treatment with IMM-101 or related mycobacterial immunotherapy.
* Serum albumin \< 26 g/L.
* C-reactive protein (CRP) \> 70 mg/L.
* Radiotherapy in the 6 weeks prior to screening.
* Depot corticosteroids in the 6 weeks prior to screening.
* Chronic use of any systemic corticosteroids and/or immunosuppressant drugs 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.
* Female patient who were pregnant, breast feeding or planning a pregnancy during the course of the study. A pre-treatment serum pregnancy test measuring human chorionic gonadotrophin (hCG) had to be negative.
* Had been administered any investigational product e.g. drug, vaccine or device, in the 3 months prior to screening.
* 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.
* Any uncontrolled concomitant disease (e.g. unstable angina pectoris, congestive heart failure, myocardial infarction, arrhythmias, and 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.
* A history of serious adverse reaction or serious hypersensitivity to any drug.
* 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.
* Unable or unwilling to comply with the protocol.

Primary outcomes:
measure: Safety and Tolerability.
timeFrame: From time of Informed Consent to 30 days post last dose of study medication
Secondary outcomes:
measure: Survival
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (or longer in the case of patients who entered the long term treatment sub-study, up to 5 years).
measure: Overall Response Rate (ORR).
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (or longer in the case of patients who entered the long term treatment sub-study).
measure: Overall Survival in Metastatic Patients Only
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (or longer in the case of patients who entered the long term treatment sub-study, up to 5 years).
Other outcomes:
Locations:
city: Nicosia
country: Cyprus
facility: Cyprus Oncology Centre
state: Strovolos
city: Dublin
country: Ireland
facility: Adelaide, Meath & National Childrens Hospital,
city: Dublin
country: Ireland
facility: St Vicents University Hospital
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna
city: Cuneo
country: Italy
facility: A.O. Santa Croce e Carle, Struttura Complessa di Oncologia Medica
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo Struttura Complessa Oncologia Medica
city: Novara
country: Italy
facility: AOU Maggiore della Carità
city: Oviedo
country: Spain
facility: Medical Oncology Department, Central University Hospital of Asturias
state: Asturias
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: Department of Medical Oncology, Hospital Universitari La Fe,
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
city: Skipton
country: United Kingdom
facility: Airedale General Hospital
state: West Yorkshire
city: Blackburn
country: United Kingdom
facility: Royal Blackburn Hospital
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Dundee
country: United Kingdom
facility: Ninewells Hospital,
city: London
country: United Kingdom
facility: Mount Vernon Cancer Centre
city: London
country: United Kingdom
facility: The London Clinic Cancer Centre
city: Peterborough
country: United Kingdom
facility: Peterbrough City Hospital, Haematology/Oncology Dept,
Study officials:
affiliation: St George's, University of London
name: Angus Dalgleish, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dalgleish AG, Stebbing J, Adamson DJ, Arif SS, Bidoli P, Chang D, Cheeseman S, Diaz-Beveridge R, Fernandez-Martos C, Glynne-Jones R, Granetto C, Massuti B, McAdam K, McDermott R, Martin AJ, Papamichael D, Pazo-Cid R, Vieitez JM, Zaniboni A, Carroll KJ, Wagle S, Gaya A, Mudan SS. Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer. Br J Cancer. 2016 Sep 27;115(7):789-96. doi: 10.1038/bjc.2016.271. Epub 2016 Sep 6.