A Trial Comparing Gemcitabine With and Without IMM-101 in Advanced Pancreatic Cancer

NCT ID: NCT01303172

Last Updated: 2021-11-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2016-01-31

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.

Conditions

Advanced Pancreatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 prescribing information for pancreatic cancer.

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

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.

IMM-101 in addition to gemcitabine

Patients in the experimental arm will receive IMM-101 in addition to 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 (Gemcitabine) will begin at least 14 days after first dose of IMM-101.

Chemotherapy plus IMM-101 will be offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles (i.e. approximately 48 weeks).

Patients who complete the Main Study and who provide informed consent are eligible to participate in a long term treatment Sub-Study (IMM-101-002A)

Group Type: EXPERIMENTAL

IMM-101

Intervention Type: BIOLOGICAL

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.

Interventions

IMM-101

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.

Intervention Type: BIOLOGICAL

Gemcitabine

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.

Intervention Type: DRUG

Other Intervention Names

Heat killed whole cell Mycobacterium obuense (M. obuense); Gemzar

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Immodulon Therapeutics Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angus Dalgleish, Professor

Role: PRINCIPAL_INVESTIGATOR

St George's, University of London

Locations

Cyprus Oncology Centre

Nicosia, Strovolos, Cyprus

Adelaide, Meath & National Childrens Hospital,

Dublin, , Ireland

St Vicents University Hospital

Dublin, , Ireland

Azienda Ospedaliero-Universitaria di Bologna

Bologna, , Italy

A.O. Santa Croce e Carle, Struttura Complessa di Oncologia Medica

Cuneo, , Italy

Azienda Ospedaliera San Gerardo Struttura Complessa Oncologia Medica

Monza, , Italy

AOU Maggiore della Carità

Novara, , Italy

Medical Oncology Department, Central University Hospital of Asturias

Oviedo, Principality of Asturias, Spain

Hospital General de Alicante

Alicante, , Spain

Hospital Gregorio Marañon

Madrid, , Spain

Instituto Valenciano de Oncologia

Valencia, , Spain

Department of Medical Oncology, Hospital Universitari La Fe,

Valencia, , Spain

Hospital Miguel Servet

Zaragoza, , Spain

Airedale General Hospital

Skipton, West Yorkshire, United Kingdom

Royal Blackburn Hospital

Blackburn, , United Kingdom

Bradford Royal Infirmary

Bradford, , United Kingdom

Velindre Cancer Centre

Cardiff, , United Kingdom

Ninewells Hospital,

Dundee, , United Kingdom

Mount Vernon Cancer Centre

London, , United Kingdom

The London Clinic Cancer Centre

London, , United Kingdom

Peterbrough City Hospital, Haematology/Oncology Dept,

Peterborough, , United Kingdom

Countries

Cyprus; Ireland; Italy; Spain; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 27599039 (View on PubMed)

Other Identifiers

IMAGE-1

Identifier Type: OTHER

Identifier Source: secondary_id

IMM-101-002

Identifier Type: -

Identifier Source: org_study_id