Phase II study evaluating Holmium-166 TARE followed by maIntenance Therapy in liver limited unresectable colorectal cancer patients after first-lIne chemotherapy and target agents: The HAITI study.
- Conditions
- iver limited unresectable colorectal cancerMedDRA version: 20.0Level: LLTClassification code: 10079136Term: Adenocarcinoma of colon metastatic Class: 10029104MedDRA version: 21.0Level: LLTClassification code: 10001172Term: Adenocarcinoma of colon stage IV Class: 10029104MedDRA version: 20.0Level: PTClassification code: 10001167Term: Adenocarcinoma of colon Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-505356-22-00
- Lead Sponsor
- Gruppo Oncologico Del Nord Ovest
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 46
Written informed consent to study procedures, Renal function: creatinine clearance > 50 mL/min or serum creatinine 1.5 x UNL; no renal disease that would preclude study treatment or follow-up, Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient, Subjects and their partners must be willing to avoid pregnancy during the trial. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as outlined in Section 7.5 – Contraception, starting during study screening visit throughout the study period up to 180 days after the last dose of chemotherapy, Will and ability to comply with the protocol, RAS/BRAF wild-type and left sided primary tumor (for Cohort A), First-line induction chemotherapy regimen permitted up to 6-12 cycles with: FOLFOX or FOLFIRI + anti-EGFR (cetuximab or panitumumab) (for Cohort A), RAS mutated and/or right-sided primary tumor (for Cohort B), First-line induction chemotherapy regimen admitted up to 6-12 cycles with: FOLFOX/FOLFIRI/XELOX + bevacizumab or FOLFOXIRI + bevacizumab (for Cohort B), Age =18 years, Histologically proven diagnosis of colorectal adenocarcinoma, with or without primary tumour in situ, Liver-only disease at radiological exams involving less than 50% of liver volume, Eastern Cooperative Oncology Group Performance Status (ECOG PS) =2, Patients with partial response or stable disease according to RECIST 1.1 criteria deemed unresectable after 6-12 cycles of induction first-line chemotherapy, Life expectancy of at least 12 weeks, Hematopoietic function: absolute neutrophil count = 1,500/mm3; platelet count =100,000/mm3; haemoglobin level = 9 g/dL, Liver function: total bilirubin = 1.5 times upper limit of normal (ULN); alkaline phosphatase = 5 times ULN; AST = 5 times
Patients with radiological evidence of extra liver distant metastases, History of a previous allergic reaction to contrast media that would preclude safe angiography of the hepatic arteries, in the opinion of the treating Interventional Radiologist, Known hypersensitivity to fluoropyrimidine, anti-VEGF or anti-EGFR MoAb, Psychiatric or addictive disorders, or other conditions that, in the opinion of the investigator, would preclude study participation, Withdrawal of the consent to take part to the study, Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis, or any other contraindications to radioembolization treatment, Previous radiotherapy delivered to the liver, Patients with BRAF mutated and/or MSI-high tumours, Previous history of malignancy within the last 5 years will be excluded with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ, Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer), Active uncontrolled infections or other clinically relevant concomitant illness contraindicating study procedures and treatment administration, Clinically significant (e.g. active) cardiovascular disease for example cerebrovascular accidents (=6 months), myocardial infarction (=6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication, Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study and until 180 days after the last trial treatment
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of Cohort A is to assess the efficacy of 166Ho-TARE followed by maintenance therapy with fluoropyrimidine and anti-EGFR in terms of progression free rate at 9 months.<br>The primary objective of Cohort B is to assess the efficacy of 166Ho-TARE followed by maintenance therapy with fluoropyrimidine and anti-VEGF in terms of progression free rate at 8 months.;Secondary Objective: Safety profile, DCR according to RECIST 1.1 criteria, Progression free survival (PFS), Overall survival (OS), Dose-response relationship between tumor absorbed doses on SPECT/CT and progression free rate, tumor response and OS, Quality of life (QoL), Translational analyses;Primary end point(s): Progression-free survival (PFS) Rate at 9- and 8-months for Cohort A and B, respectively
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Overall Toxicity rate;Secondary end point(s):G3/4 Toxicity rate;Secondary end point(s):Post-treatment DCR;Secondary end point(s):Progression free survival (PFS);Secondary end point(s):Overall Survival (OS);Secondary end point(s):Dose-response relationships;Secondary end point(s):Quality of Life