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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Cologne

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Aug 2021 → ongoing

Decision date (initial)

2024-09-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

SERVIER (Les Laboratoires Servier, France)

External identifiers

EU CT number

2024-512951-18-00

EudraCT number

2019-002734-37

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To assess the efficacy of neoadjuvant NAPOX chemotherapy followed by R0/R1 resection in patients with hepatic oligometastatic adenocarcinoma of the pancreas

Secondary objectives 3

1. To determine efficacy and safety of the treatment concept
2. To determine health-related quality of life (HR QoL)
3. To analyse HR QoL-adjusted overall survival

Conditions and MedDRA coding

Hepatic Oligometastatic Adenocarcinoma of the Pancreas

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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. 2. Measurable disease according to RECIST v1.1
3. 3. ECOG performance status 0-1
4. 4. Adequate renal, hepatic and bone marrow function, defined as o Calculated creatinine clearance ≥60 mL/min according to CKD-EPI formula o Total bilirubin ≤2 mg/dL; patients with biliary stent may be included if bilirubin level decreased to ≤2 mg/dL after stent insertion o ALT and AST ≤5 × upper limit of normal (ULN) o Absolute neutrophil count (ANC) ≥1.5 × 109/L o Thrombocytes ≥100 × 109/L o Haemoglobin ≥9 g/dL o aPTT ≤1.5 × ULN and Quick value ≥70%
5. 5. Patients ≥18 years at the time of signing the informed consent
6. 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. 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. 8. Patient's written informed consent prior to any trial-specific procedure
9. 9. Patient's legal capacity to consent to participation in the clinical trial

Exclusion criteria 29

1. 1. Acinar cell carcinoma and/or neuroendocrine carcinoma of the pancreas
2. 2. Symptomatic clinically significant ascites
3. 3. Evidence of any distant metastases other than limited hepatic metastasis as defined in inclusion criterion 1
4. 4. Any tumour-specific pretreatment of the adenocarcinoma of the pancreas (including but not limited to surgery, radiation therapy, XML File Identifier: 8QZTBq8qWrCz92BKEgr7q6YbXkk= Page 24/39 chemotherapy or ablative procedures)
5. 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. 6. Hypersensitivity to any of the IMPs or any of the excipients
7. 7. Any major surgery within 4 weeks before the first IMP administration
8. 8. Pregnant or breast-feeding female
9. 9. Known chronic inflammatory bowel disease, bowel obstruction, chronic diarrhea, Grade ≥2 according to NCI CTCAE version 5.0
10. 10. Peripheral polyneuropathy, Grade ≥ 2 according to NCI CTCAE version 5.0
11. 11. Known interstitial lung disease or pulmonary fibros
12. 12. Radiographic evidence of severe portal hypertension
13. 13. Liver cirrhosis ≥ Child Pugh B
14. 14. Cholangitis despite adequate biliary stents; treatment with anti-infective agents is permitted; the patient must be disease-free for 3 days before the first IMP administration
15. 15. Active infection requiring systemic therapy
16. 16. Known HIV seropositivity
17. 17. Active or chronic Hepatitis B or Hepatitis C infection
18. 18. Known glucoronidation deficiency (Gilbert's syndrome) (specific screening not required)
19. 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. 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. 21. Pulmonary embolism, deep venous thrombosis or arterial thromboembolism ≤1 months before the first IMP administration
22. 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. 23. Requirement for live vaccination within 4 weeks before the first IMP administration and during neoadjuvant chemotherapy
24. 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. 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. 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 until 28 days after last administration of any IMP
27. 27. Continuing abuse of alcohol, drugs or medical drugs
28. 28. Patient committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
29. 29. Patients possibly dependent from the investigator including the spouse, children and close relatives of any investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival after R0/R1 resection (OS-res) (only patients with R0/R1 resection)

Secondary endpoints 7

1. R0/R1 resection rate after neoadjuvant chemotherapy
2. Overall Survival
3. Progression-free survival (PFS) after R0/R1 resection according to RECIST v1.1
4. Type, frequency and severity of adverse events with severity according to NCI CTCAE version 5.0 (neoadjuvant chemotherapy)
5. Perioperative morbidity and mortality
6. HR-QoL according to EORTC QLQ-C30 and EORTC QLQ-PAN26 questionnaires
7. HR-QoL-adjusted OS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Cologne

Sponsor organisation

University Of Cologne

Address

Albertus-Magnus-Platz 1

City

Cologne

Postcode

50923

Country

Germany

Scientific contact point

Organisation

University Of Cologne

Contact name

Sponsor Delegated Person

Public contact point

Organisation

University Of Cologne

Contact name

Sponsor Delegated Person

Third parties 3

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications