Hepatic arterial infusion PUMP chemotherapy combined with systemIc chemoTherapy for potentially resectable colorectal liver metastases. - The PUMP-IT study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04], Diseases [C] - Neoplasms [C04]

Trial duration

10 Sep 2020 → ongoing

Decision date (initial)

2024-11-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515525-28-00

EudraCT number

2019-003260-44

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The primary objective of the study is feasibility of the HAIP chemotherapy and concomitant systemic chemotherapy (i.e. FOLFOX and FOLFIRI) in patients with liver limited CRC in 2 centers in the Netherlands.

Secondary objectives 6

1. Safety (surgical complications and chemotherapy toxicity)
2. response rates
3. Progression Free Survival (PFS)
4. Overall Survival (OS)
5. Conversionrates
6. Quality of Life (QOL)

Conditions and MedDRA coding

colorectal adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥ 18 years.
2. ECOG performance status 0 or 1.
3. Life expectancy of at least 12 weeks.
4. Histologically confirmed colorectal adenocarcinoma
5. Indication for first or second line systemic therapy, confirmed in a multidisciplinary meeting.
6. Potentially resectable (i.e. unresectable and upfront resectable CRLM with indication for neoadjuvant systemic therapy), confirmed in a multidisciplinary meeting and radio-logically on (PET) CT thorax/abdomen and/or MRI obtained ≤ 4 weeks prior to regis-tration.
7. Positioning of a catheter for HAIP chemotherapy is technically feasible confirmed in the multidisciplinary liver meeting based on imaging. The default site for the catheter inser-tion is the gastroduodenal artery (GDA). Accessory or aberrant hepatic arteries are no contra-indication for catheter implantation. The GDA should have at least one branch to the liver, accessory or aberrant hepatic arteries should be ligated to allow for cross perfusion to the entire liver through intrahepatic shunts.
8. Indication and eligibility for abdominal surgery confirmed in a multidisciplinary meeting, e.g. primary tumour resection, stoma revision/reversal and diagnostic surgery.
9. In case of primary tumour in situ: tumour should be (potentially) resectable, confirmed in a multidisciplinary meeting.
10. Adequate bone marrow, liver and renal function as assessed by the following labora-tory requirements to be conducted within 15 days prior to inclusion: o Hb ≥ 5.5 mmol/L o Absolute neutrophil count (ANC) ≥1.5 * 109/L o Platelets ≥100 * 109/L o Total bilirubin < 1.5 mg/dL o ASAT ≤ 5 * times the upper limit of normal (ULN) o ALAT ≤ 5 * ULN o Alkaline phosphatase ≤ 5 * ULN o (estimated) glomerular filtration rate (eGFR) > 45 ml/min.
11. Before patient registration, written informed consent must be given and signed accord-ing to ICH-GCP, and national/local regulations

Exclusion criteria 13

1. Extrahepatic metastases. Confirmed with CT thorax/abdomen obtained ≤ 4 weeks prior to registration. Patients with small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases are eligible.
2. Prior hepatic radiation, resection (other than biopsy), or ablation.
3. Concurrent malignancies that interfere with the planned study treatment or the progno-sis of CRLM.
4. Participation in other clinical trials interfering with the study treatment as judged by the treating physician.
5. Dihydropyrimidine dehydrogenasedeficiency (DPD deficiency).
6. Pregnant or lactating women.
7. Serious concomitant systemic disorders that would compromise the safety of the pa-tient or his/her ability to complete the study, at the discretion of the investigator.
8. Organ allografts requiring immunosuppressive therapy.
9. Serious, non-healing wound, ulcer, or bone fracture.
10. Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equiv-alent excluding inhaled steroids).
11. Serious infections (uncontrolled or requiring treatment).
12. History of psychiatric disability judged by the investigator to potentially hamper compli-ance with the study protocol and follow-up schedule.
13. Any psychological, familial, sociological or geographical condition potentially hamper-ing compliance with the study protocol and follow-up schedule.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this feasibility study is feasibility, presented as the percentage of in-cluded patients scheduled for surgery which can be treated with at least 2 cycles of HAIP chemotherapy combined with concomitant systemic chemotherapy.

Secondary endpoints 7

1. Safety: postoperative complications (defined according to Clavien-Dindo surgical complications score. Complications of Clavien-Dindo grade 3 or higher are recorded for the first 90 days after surgery. Postoperative complications include those related to the HAIP implantation. Postoperative mortality id defined as any death during hospitalization or within 90 days from surgery.
2. Safety: Drug treatment toxicity Toxicity grade 3 or higher will be recorded from the time of study inclusion according to the CTCAE version 5.0
3. Safety: Other adverse events Treatment related serious adverse events (SAE) and adverse events (AE) of grade 3 or higher will be collected continuously from the time of study inclusion until the end of combined chemotherapy.AE are followed up until the event is either resolved or adequately explained, even after the patient has completed his/her study treatment. Nature and duration of any hospitalization, treatment of any AE, and nature and duration of any outpatient care will be recorded.
4. Response rates of CRLM will be measured according to RECIST 1.1 criteria version 5.0
5. PFS will be defined from inclusion date until disease progression.
6. OS will be defined from inclusion date until death.
7. Conversion rate is defined as the percentage of patients in whom CRLM convert from an unresectable to a resectable state and undergo surgical treatment with curative intent. Possibility of local treatment is at the discretion of the multidisciplinary liver panel.

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Koert Kuhlmann

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Koert Kuhlmann

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 8 files

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

Application history

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