E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced pancreatic cancer |
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E.1.1.1 | Medical condition in easily understood language |
Locally advanced pancreatic cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033606 |
E.1.2 | Term | Pancreatic cancer non-resectable |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This phase I/II study consists of 2 subsequent study parts. In the phase I part we will investigate the safety of combining IMM-101 administration with SBRT in 20 patients with locally advanced pancreatic cancer who have completed at least 4 cycles of FOLFIRINOX chemotherapy. If deemed safe and feasible (defined as max 6 out of 20 patients experiencing a grade 4/5 toxicity related to the IMM-101 intervention) we will continue inclusion in phase II with an additional 18 patients in order to be able to study efficacy of combining IMM-101 treatment with SBRT based on a 20% improvement of 1-year disease free survival. |
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints will be overall survival, time to locoregional progression, time to distant metastasis, feasibility, safety/toxicity, resection rate, tumor specific immune-responses and quality of life/sleep. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 [26] 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. • No direct tumor involvement oft he stomach, colon or small bowel. • 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.
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E.4 | Principal 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).
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I 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.
Phase II 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 Progression Free Survival (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.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase I: Last visist patient number 20
Phase II: LPLV |
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E.5.2 | Secondary end point(s) |
For all patients the following secondary endpoints will be determined: • Overall survival (OS). • Time to locoregional progression, defined as the period of time without locoregional progression after inclusion. • Time to distant metastasis, defined as the period of time without distant metastases after inclusion. • Radiological response rate after IMM-101 and SBRT using RECIST criteria (version 1.1) • Resection rate defined as the percentage of included patients that underwent a curative-intent resection. • 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). • Safety/Toxicity according to CTCAE 5.0. • Tumor-specific immune responses. • Quality of sleep and sleep duration. • Quality of life.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |