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.

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.