Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04617457
Other study ID # Uni-Koeln-4067
Secondary ID 2019-002734-3720
Status Recruiting
Phase Phase 2
First received
Last updated
Start date October 10, 2021
Est. completion date September 30, 2025

Study information

Verified date January 2024
Source University of Cologne
Contact Florian Gebauer, MD
Phone +492028961563
Email florian.gebauer@helios-gesundheit.de
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is an interventional, open-label, non-randomised, multicentre, single-arm phase II clinical trial. Eligible patients with hepatic oligometastatic adenocarcinoma of the pancreas will receive neoadjuvant combination chemotherapy (liposomal irinotecan, oxaliplatin, 5-fluouracil, folinic acid (NAPOX)) in cycles of 14 days. Patients with tumour response or stable disease and a resectable primary tumour after the first 4 cycles will undergo explorative laparotomy and synchronous resection of the tumour and hepatic metastases, if feasible; these patients may receive 4 more cycles of neoadjuvant chemotherapy 2-4 weeks after the explorative laparotomy if the surgeon rated the primary tumour as non-resectable during the explorative laparotomy.


Description:

This is an interventional, open-label, non-randomised, multicentre, single-arm phase II clinical trial. Eligible patients with hepatic oligometastatic adenocarcinoma of the pancreas will receive neoadjuvant NAPOX chemotherapy in cycles of 14 days. In patients with progressive disease during or after the first 4 cycles, neoadjuvant chemotherapy will be permanently discontinued. Patients with tumour response or stable disease after the first 4 cycles according to RECIST v1.1 but a non-resectable primary tumour according to the evaluation of an interdisciplinary tumour board will receive 4 more cycles of neoadjuvant chemotherapy. Patients with tumour response or stable disease and a resectable primary tumour after the first 4 cycles will undergo explorative laparotomy and synchronous resection of the tumour and hepatic metastases, if feasible; these patients may receive 4 more cycles of neoadjuvant chemotherapy 2-4 weeks after the explorative laparotomy if the surgeon rated the primary tumour as non-resectable during the explorative laparotomy. All patients who receive a total of 8 cycles and who then have tumour response or stable disease according to RECIST v1.1 will undergo exploratory laparotomy surgery and synchronous resection of the tumour and hepatic metastases, if feasible according to the surgeon, 2-6 weeks after the last investigational medicinal product (IMP) treatment. The primary endpoint of the clinical trial is overall survival of patients with an R0/R1 resection after neoadjuvant chemotherapy. The IMP treatment will be discontinued if tumour progression or inacceptable toxicity occurs or other termination criteria apply. Adjuvant treatment will not be part of the trial treatment and may be given at the investigator's discretion in accordance with the Onkopedia guideline for pancreatic cancer. Tumour, stool and blood samples will be collected before start and during the clinical trial for translational research if the patient gives his/her consent to participating in the translational research programme.


Recruitment information / eligibility

Status Recruiting
Enrollment 150
Est. completion date September 30, 2025
Est. primary completion date December 31, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 (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 5 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. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 4. Adequate renal, hepatic and bone marrow function, defined as - Calculated creatinine clearance =60 mL/min - Total bilirubin =2 mg/dL; patients with biliary stent may be included if bilirubin level decreased to =2 mg/dL after stent insertion - alanin-aminotransferase and aspartat-aminotransferase (ALT and AST) =5 × upper limit of normal (ULN) - Absolute neutrophil count (ANC) =1.5 × 109/L - Thrombocytes =100 × 109/L - Haemoglobin =9 g/dL - activated partial thromboplastin time (aPTT) =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 1 month 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 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 or chronic diarrhoea 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 (ILD) 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 glucuronidation deficiency (Gilbert's syndrome) (specific screening not required) 19. Known complete dihydropyrimidine dehydrogenase (DPD) deficiency (specific screening according to the recommendations of the Summary of Product Characteristics (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 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 New York Heart Association (NYHA) = Grade 2, uncontrolled arrhythmia, cerebral infarction) 21. Pulmonary embolism, deep venous thrombosis or arterial thromboembolism =6 months before 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 first IMP administration, depending on which period is longest, or simultaneous participation in another clinical trial while taking part in this clinical trial 27. Continuing abuse of alcohol, drugs or medical drugs 28. Patient committed to an institution by virtue of an order issued either by the judicial or the administrative authorities 29. Patients possibly dependent from the investigator including the spouse, children and close relatives of any investigator at the discretion of the investigator)

Study Design


Intervention

Drug:
nal-irinotecan (nal-iri) (Onyvide), oxaliplatin (ox), 5-fluouracil (5-FU), folinic acid (FA)
preoperative chemotherapy

Locations

Country Name City State
Germany University Aachen Aachen
Germany University of Berlin, Charité, Campus Benjamin-Franklin Berlin
Germany University of Bonn Bonn
Germany Städtisches Klinikum Dresden Dresden
Germany University of Düsseldorf Düsseldorf
Germany University of Freiburg Freiburg
Germany University of Halle (Saale) Halle (Saale)
Germany University of Heidelberg Heidelberg
Germany Klinikum Großhadern, LMU München München
Germany Klinikum Rechts der Isar Technische Universität München München
Germany University of Regensburg Regensburg

Sponsors (2)

Lead Sponsor Collaborator
University of Cologne Servier

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Gebauer F, Damanakis AI, Popp F, Quaas A, Kutting F, Lutz K, Held S, Deuss B, Goser T, Waldschmidt D, Bruns C. Study protocol of an 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). BMC Cancer. 2021 Nov 18;21(1):1239. doi: 10.1186/s12885-021-08966-3. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Overall survival after R0/R1 resection (OS-res) OS for patient after macroscopic tumor resection max 24 months follow-up
Secondary R0/R1 resection rate after neoadjuvant chemotherapy Fraction of patients that undergo macroscopically complete tumor resection (No and %) direct after operation
Secondary Overall survival (OS) time from study inclusion until death (months) max 24 months follow-up
Secondary Progression-free survival (PFS) after R0/R1 resection according to RECIST v1.1 time from study inclusion until tumor progress/recurrence (months) max 24 months follow-up
Secondary Type, frequency and severity of adverse events (AE) with severity (SAE) according to NCI CTCAE version 5.0 Number and fraction of AE/SAEs (No and %) direct after IMP administration up to 3 months after completion of study
Secondary HR-QoL according to EORTC QLQ-C30 Quality of Life according to the EORTC QLQ-C30 questionaire (scale 0 (poor) - 7 (excellent) 90 days after operation
Secondary Quality of life (QoL) according to EORTC QLQ-PAN-26 Quality of Life according to the EORTC QLQ-PAN26 questionaire (scale 0 (poor) - 7 (excellent) 90 days after operation
Secondary QoL-adjusted OS time from study inclusion until death (months) adjusted to quality of life max 24 months follow-up
See also
  Status Clinical Trial Phase
Completed NCT05305001 - Germline Mutations Associated With Hereditary Pancreatic Cancer in Unselected Patients With Pancreatic Cancer in Mexico
Completed NCT02526017 - Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers Phase 1
Recruiting NCT05497531 - Pilot Comparing ctDNA IDV vs. SPV Sample in Pts Undergoing Biopsies for Hepatobiliary and Pancreatic Cancers N/A
Recruiting NCT04927780 - Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer Phase 3
Recruiting NCT06054984 - TCR-T Cells in the Treatment of Advanced Pancreatic Cancer Early Phase 1
Recruiting NCT05919537 - Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation Phase 1
Terminated NCT03140670 - Maintenance Rucaparib in BRCA1, BRCA2 or PALB2 Mutated Pancreatic Cancer That Has Not Progressed on Platinum-based Therapy Phase 2
Terminated NCT00529113 - Study With Gemcitabine and RTA 402 for Patients With Unresectable Pancreatic Cancer Phase 1
Recruiting NCT05168527 - The First Line Treatment of Fruquintinib Combined With Albumin Paclitaxel and Gemcitabine in Pancreatic Cancer Patients Phase 2
Active, not recruiting NCT04383210 - Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors Phase 2
Recruiting NCT05391126 - GENOCARE: A Prospective, Randomized Clinical Trial of Genotype-Guided Dosing Versus Usual Care N/A
Terminated NCT03300921 - A Phase Ib Pharmacodynamic Study of Neoadjuvant Paricalcitol in Resectable Pancreatic Cancer A Phase Ib Pharmacodynamic Study of Neoadjuvant Paricalcitol in Resectable Pancreatic Cancer Phase 1
Completed NCT03153410 - Pilot Study With CY, Pembrolizumab, GVAX, and IMC-CS4 (LY3022855) in Patients With Borderline Resectable Adenocarcinoma of the Pancreas Early Phase 1
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2
Recruiting NCT05679583 - Preoperative Stereotactic Body Radiation Therapy in Patients With Resectable Pancreatic Cancer Phase 2
Recruiting NCT04183478 - The Efficacy and Safety of K-001 in the Treatment of Advanced Pancreatic Cancer Phase 2/Phase 3
Terminated NCT03600623 - Folfirinox or Gemcitabine-Nab Paclitaxel Followed by Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer Early Phase 1
Recruiting NCT04584008 - Targeted Agent Evaluation in Digestive Cancers in China Based on Molecular Characteristics N/A
Recruiting NCT05351983 - Patient-derived Organoids Drug Screen in Pancreatic Cancer N/A
Completed NCT04290364 - Early Palliative Care in Pancreatic Cancer - a Quasi-experimental Study