Extended Criteria Treatment for Liver Metastases With Heavy Tumour Burde

Phase 1

Active, not recruiting

• Conditions: Colorectal Liver Metastases; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]; Therapeutic area: Phenomena and Processes [G] - Digestive System and Oral Physiological Phenomena [G10]; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: CTIS2024-512397-95-00
• Lead Sponsor: Oslo University Hospital HF

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-06-14
• Last Update Posted: 2024-07-22

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 97

Inclusion Criteria

Primary histology: verified adenocarcinoma in colon or rectum, Liver metastases: a. Not possible or feasible to resect at time of inclusion. b. Resection will require 10 % or more response in index lesions. c. And one of the following: I Insufficient response on current line chemotherapy and in need of next line systemic chemotherapy or major change of active agents as judged by treating oncologist (I, IIa, IIb). II Treatment stopped due to toxicity, and hence in need of next line systemic chemotherapy (I, IIa, IIb). III Stable disease or partial response (RECIST) is achieved following first cycle of 1st. line conventional chemotherapy (4 doses), but minimal probability of reaching liver surgery (IIc) due to any of the following: i. > 6 lesions with bi-lobar distribution and CEA > 1.000, or ii. > 10 lesions with bi-lobar distribution and at least one lesion with a diameter > 5 cm, or iii. > 15 lesions with bi-lobar distribution, Chemotherapy: a. Patients must have received at least one line of systemic chemotherapy at time of inclusion in the study. Planned for next line chemotherapy (I, IIa, IIb). b. If patients have commenced next line chemotherapy, randomization can only be allowed prior to first evaluation on next line chemotherapy regimen (I, IIa, IIb). c. For IIc, patients must have undergone one cycle of systemic conventional chemotherapy and only have stable disease or partial response at first evaluation, but with a response insufficient for resection., The patient: a. Good performance status, ECOG 0 or 1. b. Satisfactory blood tests: Hb >9 g/dl, neutrophiles >1.0 (after any G-CSF), TRC >75, Bilirubin<1.5 x upper normal level, ASAT, ALAT<5 x upper normal level, Creatinine <1.25 x upper normal level. Albumin above lower normal level. c. Women of childbearing potential (WOCBP) must have a confirmed menstrual cycle and a negative highly sensitive pregnancy test prior to inclusion, or two negative pregnancy tests two weeks apart d. WOCBP must agree to use a highly effective method of contraception (see section 6.1.2) for the entire period of exposure to the IMP in the trial, plus for one menstrual cycle/30 days after the last exposure due to the genotoxic potential of the IMP e. Men that may have sexual relations with a WOCBP during the trial must agree to use a condom during intercourse for the entire period of exposure plus for one sperm cycle / 90 days after the last exposure due to the genotoxic potential of the IMP, Signed informed consent and expected cooperation of the patients for treatment and follow up must be obtained and documented according to GCP, and national/local regulations.

Exclusion Criteria

Arterial anatomy not suited for HAI pump-line insertion., A primary tumour in situ that is either a a. Rectal tumour scheduled for radiation therapy with fractionation 2 Gy x 25, or b. A right-sided or transverse colonic tumour, Previous or current bone or CNS metastatic disease., Patients with known intolerance or allergy to any ingredient of the IMP to be used as standard therapy for that patient, Breastfeeding women, Patients with a psychiatric condition that makes participation in the trial impossible or unethical, Patients in a poor nutritional state, those with depressed bone marrow function or those with potentially serious infections must be excluded., Any other reason why, in the opinion of the investigators, the patient should not participate., Exclusion Excalibur I: Any of the following will preclude inclusion into Excalibur I (but not into Excalibur IIa/b/c): 1. BRAF positivity 2. Any sign of extra-hepatic metastatic disease or local recurrence on PET/CT scan, and on CT or MRI thorax/abdomen/pelvis dated within 6 weeks prior to the trial hospital MDT meeting (exception allowed for <3 resectable lung lesions all < 15mm). 3. Liver lesion >10cm 4. Patient BMI > 30 5. Any previous non-colorectal malignancy within latest five years with the exception of basal cell carcinoma of the skin. 6. Age > 70 years 7. Liver metastatic ingrowth to the diaphragm determined by CT-scan and/or MRI/or ultrasound 8. Any primary tumour in situ

Study & Design

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