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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gruppo Oncologico Del Nord Ovest

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Mar 2024 → 14 Nov 2025

Decision date (initial)

2023-12-18

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

TERUMO Europe NV · Fondazione GONO

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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.
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 objectives 7

1. Safety profile
2. DCR according to RECIST 1.1 criteria
3. Progression free survival (PFS)
4. Overall survival (OS)
5. Dose-response relationship between tumor absorbed doses on SPECT/CT and progression free rate, tumor response and OS
6. Quality of life (QoL)
7. Translational analyses

Conditions and MedDRA coding

Liver limited unresectable colorectal cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Written informed consent to study procedures
2. Age ≥18 years
3. Histologically proven diagnosis of colorectal adenocarcinoma, with or without primary tumour in situ
4. Liver-only disease at radiological exams involving less than 50% of liver volume
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2
6. Patients with partial response or stable disease according to RECIST 1.1 criteria deemed unresectable after 6-12 cycles of induction first-line chemotherapy
7. Life expectancy of at least 12 weeks
8. Hematopoietic function: absolute neutrophil count ≥ 1,500/mm3; platelet count ≥100,000/mm3; haemoglobin level ≥ 9 g/dL
9. Liver function: total bilirubin ≤ 1.5 times upper limit of normal (ULN); alkaline phosphatase ≤ 5 times ULN; AST ≤ 5 times ULN
10. 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
11. 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
12. 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
13. Will and ability to comply with the protocol
14. RAS/BRAF wild-type and left sided primary tumor (for Cohort A)
15. First-line induction chemotherapy regimen permitted up to 6-12 cycles with: FOLFOX or FOLFIRI + anti-EGFR (cetuximab or panitumumab) (for Cohort A)
16. RAS mutated and/or right-sided primary tumor (for Cohort B)
17. First-line induction chemotherapy regimen admitted up to 6-12 cycles with: FOLFOX/FOLFIRI/XELOX + bevacizumab or FOLFOXIRI + bevacizumab (for Cohort B)

Exclusion criteria 13

1. Patients with radiological evidence of extra liver distant metastases
2. Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis, or any other contraindications to radioembolization treatment
3. Previous radiotherapy delivered to the liver
4. Patients with BRAF mutated and/or MSI-high tumours
5. 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
6. Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer)
7. Active uncontrolled infections or other clinically relevant concomitant illness contraindicating study procedures and treatment administration
8. 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
9. 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
10. 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
11. Known hypersensitivity to fluoropyrimidine, anti-VEGF or anti-EGFR MoAb
12. Psychiatric or addictive disorders, or other conditions that, in the opinion of the investigator, would preclude study participation
13. Withdrawal of the consent to take part to the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) Rate at 9- and 8-months for Cohort A and B, respectively

Secondary endpoints 7

1. Overall Toxicity rate
2. G3/4 Toxicity rate
3. Post-treatment DCR
4. Progression free survival (PFS)
5. Overall Survival (OS)
6. Dose-response relationships
7. Quality of Life

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gruppo Oncologico Del Nord Ovest

Sponsor organisation

Gruppo Oncologico Del Nord Ovest

Address

Via Goffredo Mameli 3/1

City

Genoa

Postcode

16122

Country

Italy

Scientific contact point

Organisation

Gruppo Oncologico Del Nord Ovest

Contact name

Chiara Cremolini

Public contact point

Organisation

Gruppo Oncologico Del Nord Ovest

Contact name

Laura Delliponti

Locations

1 EU/EEA country · 8 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

Application history

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