Open-Label, Single Arm Phase II Trial Investigating the Efficacy, Safety and Quality of Life of Neoadjuvant Chemotherapy with Liposomal Irinotecan Combined with Oxaliplatin and 5-Fluorouracil/Folinic Acid Followed by Curative Surgical Resection in Patients with Hepatic Oligometastatic Adenocarcinoma of the Pancreas (HOLIPANC)

Phase 1

• Conditions: Hepatic Oligometastatic Adenocarcinoma of the Pancreas; MedDRA version: 27.0Level: PTClassification code 10033610Term: Pancreatic carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002734-37-DE
• Lead Sponsor: niversity of Cologne

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-10-13
• Last Update Posted: 13 May 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1.Histologically confirmed diagnosis of treatment-naïve limited hepatic metastatic adenocarcinoma of the pancreas
Definition of limited hepatic metastasis: 1 to 5 metastases in CT/MRI and/or contrast-enhanced ultrasound scan, which are potentially resectable or treatable by ablative procedures.. In the event that more than 5 liver metastases are detected on preoperative imaging, the patient may nevertheless be included based on an individual decision after mandatory consultation with the sponsor. This decision must take into account the complexity of the overall operation of primary tumor and metatstases, and technical resectability of the liver metastases is crucial. (Note 1: Patients also fulfil this inclusion criterion if a hepatic metastasis was partly or entirely removed as part of the diagnosis and is thus not detectable by CT/MRI and/or contrast-enhanced ultrasound scan at screening. Note 2: If more than five metastases are unexpectedly detected during surgery, it is not a violation of this inclusion criterion if the excess metastases had not been detectable by CT/MRI and/or contrast-enhanced ultrasound scan at screening.)
2.Measurable disease according to RECIST v1.1
3.ECOG performance status 0-1
4.Adequate renal, hepatic and bone marrow function, defined as
oCalculated creatinine clearance =60 mL/min according to CKD-EPI formula
oTotal bilirubin =2 mg/dL; patients with biliary stent may be included if bilirubin level decreased to =2 mg/dL after stent insertion
oALT and AST =5 × upper limit of normal (ULN)
oAbsolute neutrophil count (ANC) =1.5 × 109/L
oThrombocytes =100 × 109/L
oHaemoglobin =9 g/dL
oaPTT =1.5 × ULN and Quick value =70%
5.Patients =18 years at the time of signing the informed consent
6.Females of childbearing potential (FCBPs) must agree to use highly effective contraceptive measures (Pearl index <1) or practice true abstinence from any heterosexual intercourse for the duration of treatment and for at least 7 months after the last IMP administration (true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient). A woman will be considered as being of childbearing potential unless she is at least 50 years old and moreover has gone through menopause for at least 2 years or has been surgically sterilised.
7.Males must agree to use condoms or practice true abstinence from any heterosexual intercourse for the duration of IMP treatment and at least 6 months after the last IMP administration (true abstinence is acceptable if this is in line with the patient’s preferred and usual lifestyle). Male patients must furthermore refrain from donating sperm during the clinical trial until at least 6 months after the last IMP administration.
8.Patient's written informed consent prior to any trial-specific procedure
9.Patient’s legal capacity to consent to participation in the clinical trial

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Acinar cell carcinoma and/or neuroendocrine carcinoma of the pancreas
2.Symptomatic clinically significant ascites
3.Evidence of any distant metastases other than limited hepatic metastasis as defined in inclusion criterion 1.
4.Any tumour-specific pretreatment of the adenocarcinoma of the pancreas (including but not limited to surgery, radiation therapy, chemotherapy or ablative procedures)
5.Any malignancies other than adenocarcinoma of the pancreas in the 5 years before the start of the clinical trial except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, breast cancer, prostate cancer or superficial bladder tumours (Ta, Tis and T1)
6.Hypersensitivity to any of the IMPs or any of the excipients
7.Any major surgery within 4 weeks before the first IMP administration
8.Pregnant or breast-feeding female
9.Known chronic inflammatory bowel disease, bowel obstruction, chronic diarrhea, Grade =2 according to NCI CTCAE version 5.0
10.Peripheral polyneuropathy, Grade = 2 according to NCI CTCAE version 5.0
11.Known interstitial lung disease or pulmonary fibrosis
12.Radiographic evidence of severe portal hypertension
13.Liver cirrhosis = Child Pugh B
14.Cholestasis or cholangitis despite adequate biliary stenting; treatment with anti-infectious agents is permitted; patient must be disease-free and without anti-infectious treatment for 7 days before the first IMP administration
15.Active infection requiring systemic therapy
16.Known HIV seropositivity
17.Active or chronic Hepatitis B or Hepatitis C infection
18.Known glucoronidation deficiency (Gilbert’s syndrome) (specific screening not required)
19.Known complete dihydropyrimidine dehydrogenase (DPD) deficiency (specific screening according to the recommendations of the SmPC in effect for 5-FU; patients with a known complete DPD deficiency must be excluded; patients with a known partial DPD deficiency may be included at the discretion of the investigator
20.Clinically significant cardiovascular or vascular disease or disorder =6 months before enrolment into the clinical trial (e.g., myocardial infarction, unstable angina pectoris, chronic heart failure NYHA = Grade 2, uncontrolled arrhythmia, cerebral infarction)
21.Pulmonary embolism, deep venous thrombosis or arterial thromboembolism =1 months before the first IMP administration
22.Any other severe concomitant disease or disorder, which could influence patient’s ability to participate in the clinical trial and his/her safety during the trial or interfere with interpretation of results; e.g., severe hepatic, renal, pulmonary, cardiovascular, metabolic or psychiatric disorders
23.Requirement for live vaccination within 4 weeks before the first IMP administration and during neoadjuvant chemotherapy
24.Use of strong CYP3A4 inhibitors (Strong CYP3A4 inhibitors have to be discontinued at least one week prior to start of trial treatment.) Use of strong UGT1A1 inhibitors or strong CYP3A4 inducers unless there are no therapeutic alternatives
25.Treatment with nucleoside analogues such as brivudine within 4 weeks before the first IMP administration or requirement for concomitant antiviral treatment with brivudine or analogues
26.Participation in a clinical trial or experimental drug treatment within 4 weeks before the first IMP administration or within a period of 5 half-lives of the substances administered in a clinical trial or during an experimental drug treatment before the f

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified