Safety and efficacy of the addition of IMM-101 (Heat-Killed Whole Cell Mycobacterium obuense) to standard stereotactic radiotherapy in locally advanced pancreatic cancer patients. (LAPC-2 trial)

Recruiting

Conditions: ocally advanced pancreatic cancer (LAPC)

Registration Number: NL-OMON22166

Lead Sponsor: Erasmus MC, Surgery department

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 38

Inclusion Criteria

•Histologically confirmed pancreatic cancer, as indicated by a definite cytology report.
•Tumor considered locally advanced after diagnostic work-up including CT-imaging, using the DPCG criteria for locally advanced disease and diagnostic laparoscopy.
•Age > 18 years and < 75 years.
•WHO performance status of 0 or 1.
•ASA classification I or II.
•No evidence of metastatic disease.
•Largest tumor size < 7 cm x 7 cm x 7 cm.
•Normal renal function (Creatinine = 30 ml/min).
•Normal liver tests (bilirubin < 1.5 times normal*; ALAT/ASAT < 5 times normal).
•Normal bone marrow function (WBC > 3.0 x 10e9/L, platelets > 100 x 10e9/L and hemoglobin > 5.6 mmol/l).
•Ability to wear an Actiwatch device on non-dominant arm.
•Effective contraceptive methods.
•Written informed consent.

* If bilirubin is higher than 35 umol/L placement of a metal biliary stent is mandatory.

Exclusion Criteria

•Prior radiotherapy, chemotherapy other than FOLFIRINOX or pancreatic resection.
•Current or previous treatment with immunotherapeutic drugs.
•Previous allergic reaction to any mycobacterial product.
•Prolonged systemic corticosteroid or immunosuppressant medication use (i.e. >2 weeks).
•Lymph node metastases from primary tumor outside the field of radiation.
•Second primary malignancy except in situ carcinoma of the cervix, adequately treated non-melanoma skin cancer, or other malignancy treated at least 5 years previously to diagnosis of pancreatic cancer and without evidence of recurrence.
•Pregnancy, breast feeding.
•Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator.
•An active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
•Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the planned first dose of the study. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
•Known history of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies).
•Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
•Live virus vaccine within 30 days of planned start of trial treatment.
•Use of herbal remedies, including traditional Chinese herbal products (e.g., mistletoe).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Phase I<br>The main endpoint of the first inclusion phase is to determine safety/toxicity of IMM-101 administration in LAPC patients undergoing SBRT. Safety/toxicity of the IMM-101 intervention will be determined according to CTCAE version 5.0. All grade 4 and 5 events related to the administration of the IMM-101 product will be considered events for this endpoint.<br><br>Phase II<br>The main endpoint of the second inclusion phase is to asses efficacy of IMM-101 therapy in combination with SBRT in LAPC patients. Efficacy will be determined using 1-year PFS rates. PFS is defined as survival without locoregional progressive disease, the occurrence of distant metastases, the occurrence of second or recurrent pancreatic cancer from the date of inclusion. All included patients (i.e. 38 patients) will be analyzed for this endpoint.

Secondary Outcome Measures

Name	Time	Method
For all patients the following secondary endpoints will be determined:<br>•Overall survival.<br>•Time to locoregional progression, defined as the period of time without locoregional progression after inclusion.<br>•Time to distant metastasis, defined as the period of time without distant metastases after inclusion.<br>•Radiological response rate after IMM-101 and SBRT using RECIST criteria (version 1.1)<br>•Resection rate defined as the percentage of included patients that underwent a curative-intent resection.<br>•Feasibility of receiving IMM-101 treatment and performing follow-up. Defined as feasibility of treatment procedures in order to be able to administer IMM-101 to patients and follow up these patients (e.g. ability to collect extra blood samples at designated time points).<br>•Safety/Toxicity according to CTCAE 5.0.<br>•Tumor-specific immune responses.<br>•Quality of sleep and sleep duration.<br>•Quality of life.