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

NCT01303172 | Completed Phase 2 Results DMC

• 2 other identifiers: IMM-101-002IMAGE-1
• Study Type: interventional
• Target: 110
• Locations: 5 countries
• Sites: 21

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.

Conditions

Advanced Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability.

  A clinically relevant deleterious effect of IMM-101 on safety and tolerability profiles was 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. Adverse events were collected from time of Informed Consent to 30 days post last dose of study medication IMM-101 does not appear to confer an incremental safety burden beyond that associated with chemotherapy and the disease itself. No new safety signals were identified from this study. The numbers of SAEs by preferred term were low, such that no trends could be inferred from these data and no significant SAEs attributable to IMM 101 were observed.

  From time of Informed Consent to 30 days post last dose of study medication

Secondary Outcomes (3)

• Survival

  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).

• Overall Response Rate (ORR).

  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).

• Overall Survival in Metastatic Patients Only

  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).

Study Arms (2)

Gemcitabine chemotherapy

ACTIVE COMPARATOR

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.

Drug: Gemcitabine

IMM-101 in addition to gemcitabine

EXPERIMENTAL

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)

Biological: IMM-101

Interventions

IMM-101 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.

Also known as: Heat killed whole cell Mycobacterium obuense (M. obuense)

IMM-101 in addition to gemcitabine

Gemcitabine 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.

Also known as: Gemzar

Gemcitabine chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Immodulon Therapeutics Ltd: lead

Study Sites (21)

Cyprus Oncology Centre

Nicosia, Strovolos, 2006, Cyprus

Location

Adelaide, Meath & National Childrens Hospital,

Dublin, Dublin 24, Ireland

Location

St Vicents University Hospital

Dublin, Dublin 4, Ireland

Location

Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

Location

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

Cuneo, Italy

Location

Azienda Ospedaliera San Gerardo Struttura Complessa Oncologia Medica

Monza, 20900, Italy

Location

AOU Maggiore della Carità

Novara, Italy

Location

Medical Oncology Department, Central University Hospital of Asturias

Oviedo, Principality of Asturias, Spain

Location

Hospital General de Alicante

Alicante, 03010, Spain

Location

Hospital Gregorio Marañon

Madrid, 28007, Spain

Location

Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Department of Medical Oncology, Hospital Universitari La Fe,

Valencia, 46026, Spain

Location

Hospital Miguel Servet

Zaragoza, 50009, Spain

Location

Airedale General Hospital

Skipton, West Yorkshire, BD20 6TD, United Kingdom

Location

Royal Blackburn Hospital

Blackburn, BB2 3HH, United Kingdom

Location

Bradford Royal Infirmary

Bradford, BD9 6RJ, United Kingdom

Location

Velindre Cancer Centre

Cardiff, Velindre Cancer Centre, United Kingdom

Location

Ninewells Hospital,

Dundee, DD1 9SY, United Kingdom

Location

Mount Vernon Cancer Centre

London, HA6 2RN, United Kingdom

Location

The London Clinic Cancer Centre

London, W1G 6BW, United Kingdom

Location

Peterbrough City Hospital, Haematology/Oncology Dept,

Peterborough, PE3 9GZ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 27599039 BACKGROUND

MeSH Terms

Interventions

IMM-101; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

This proof of concept study was not formally sized to test a specific pre-defined efficacy hypothesis. However, it has provided important insights into the potential for efficacy improvements with the use of IMM-101 in combination with chemotherapy in advanced pancreatic cancer. Safety assessment based on AE \& SAE profiles in each treatment arm had limitations as GEM is associated with frequent AEs and was given in both treatment arms. Thus, assessment of causality was difficult to interpret.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Immodulon Therapeutics Ltd

info@immodulon.com

+44 (0) 20 3137 6346

Study Officials

• Angus Dalgleish, Professor

  St George's, University of London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2011
• First Posted: February 24, 2011
• Study Start: June 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: January 1, 2016
• Last Updated: November 10, 2021
• Results First Posted: September 29, 2021

Record last verified: 2021-11

Locations

CY (1); IE (2); ES (6); GB (8); IT (4)