Prospective study in patients with colon or rectum cancer with liver metastasis of the efficacy and toxicity of standard therapy (chemotherapy + targeted therapy) combined with immunotherapy and internal radiotherapy targeting the liver

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation Franc.Cancerologie Digestive

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

30 Aug 2024 → ongoing

Decision date (initial)

2024-08-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Boston scientific · ROCHE

External identifiers

EU CT number

2024-517204-11-00

EudraCT number

2019-002400-40

ClinicalTrials.gov

NCT04659382

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

evaluate the progression-free survival at 9 months (according to RECIST 1.1) according to the investigator.

Secondary objectives 11

1. safety (NCI CTCAE v4.0)
2. median progression free survival (RECIST 1.1 and immune - RECIST iRECIST )
3. liver specific progression-free survival (RECIST 1.1 and iRECIST)
4. extra-hepatic progression-free survival (RECIST 1.1 and iRECIST)
5. overall best response rate (RECIST 1.1 and iRECIST)
6. response rates at weeks 9, 18 and 27 (hepatic and non-hepatic target lesions)
7. early tumor shrinkage
8. depth of tumor response
9. secondary resectionrate
10. time to treatment strategy failure
11. biomarker analyses (ancillary studies)

Conditions and MedDRA coding

microsatellite stable (MSS) colorectal cancer with liver-dominant metastasis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. age over 18 years old
2. histologically proven mismatch repair proficient metastatic colorectal cancer (pMMR and/ or MSS)
3. liver-dominant disease with up to 6 extrahepatic lesions (only peritoneal lesions are not allowed) if asymptomatic and without organ dysfunction
4. measurable disease according to RECIST 1.1
5. patient with initially unresectable disease according to the local multidisciplinary team and eligible for radioembolization according to the radiologist's opinion
6. tumor volume < 50% of total liver volume
7. no prior oncologic treatment for metastatic disease. patients may have received adjuvant chemotherapy or (neo) adjuvant radiochemaotherapy to the pelvis but the last dose of chemotherapy / radiotherapy must be administred at least 6 months prior to entry into this study. analgesic radiotherapy of metastasis is permitted except on hepatic lesions and must be completed at least 14 days before inclusion
8. WHO performance status
9. estimated life expectancy >ou= 3
10. adequate hematological function
11. adequate hepatic function
12. adequate renal function
13. patient affiliated to a social security system information provided to patient and signature of the informed consent form by patient and the investigator

Exclusion criteria 33

1. active infection still requiring intravenous antibiotics on the first scheduled day of protocol treatment
2. Symptomatic or untreated central nervous system metastasis
3. - Medical history of other concomitant or previous malignant disease, except adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer in complete remission for ≥ 5 years
4. - Other malignancy in the 5 years prior to inclusion in the study, except for localized cancer in situ, basal or squamous cell skin cancer
5. - Confirmed peritoneal carcinomatosis (lesions detectable on CT-scan and/or MRI)
6. Active autoimmune disease or inflammatory bowel disease
7. Bone marrow allograft or solid organ transplant history
8. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis or evidence of active pneumonitis on screening chest CT-scan and any severe chronic respiratory insufficiency that the investigator believes would not allow the SIRT to be received safely
9. Positive tests for HIV or other immunodeficiency syndromes
10. Severe chronic liver failure, which in the investigator's opinion would not allow SIRT to be received safely
11. - Active hepatitis B or hepatitis C. 1 - If patient has HBV, meets the following criteria as applicable to the infection type to be eligible: for patients with inactive/asymptomatic carrier, chronic, or active HBV: HBV DNA < 500 IU/mL (or 2500 copies/mL) at screening. Patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should be managed per treatment guidelines. Patients receiving antivirals at Screening should have been treated for > 2 weeks prior to enrollment and should continue treatment on study. 2 - For patients with HCV : to be eligible, patients with detectable HCV RNA should remain on continuous, effective antiviral therapy during the study
12. Active tuberculosis
13. Patient with contraindication to angiography and selective hepatic catheterization such as bleeding diathesis or coagulopathy with serious bleeding risk that is not correctable by usual therapy of hemostatic agents.
14. Patients on anticoagulant therapy different from low-molecular-weight heparin (LMWH) cannot be included (i.e. VKA and NOACs). Relaying these anticoagulants to a LMWH before inclusion is allowed. In addition, it must be possible to stop the LMWH 24 hours before invasive procedures according to the usual recommendations (before the work-up and before the SIRT).
15. Significant presence of ascites, cirrhosis, portal hypertension, main portal venous tumor involvement or thrombosis on clinical or radiological evaluation Previous radiotherapy in the upper abdominal region (liver or liver vessels in the radiation field)
16. If primary tumor is non-resected, it must be asymptomatic
17. Long-term immunosuppressant therapy (patients requiring corticosteroid therapy are eligible if they receive a dose equivalent to no more than 10 mg of prednisone equivalent dose per day, and corticosteroid administration is permitted by a route resulting in minimal systemic exposure (cutaneous, rectal, articular, ocular or inhalation) is authorized)
18. Patient who has previously experienced a severe or life-threatening skin adverse reaction on prior treatment with an immune-stimulatory anticancer agents
19. Patient with previous Johnson Stevens Syndrome (SJS) or Toxic Epidermal Necrosis (TEN)
20. Partial or complete DPD deficiency
21. Known hypersensitivity to any components of bevacizumab, Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies and any other contraindications to the use of investigational medicinal products, in particular patients with peripheral sensory neuropathy with functional impairment (see SmPC of oxaliplatin) or in the case of recent or concomitant treatment with brivudine (see SmPC of capecitabine)
22. QT/QTc interval > 450 msec for male and > 470 msec for female at EKC
23. - K+ < LLN, Mg²+ < LLN, Ca²+ < LLNAllergy to contrast agents that do not allow radioembolization to be performed
24. Uncontrolled hypertension (blood pressure > 140 mm Hg and/or diastolic blood pressure > 90 mm Hg)
25. Clinically significant cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to the start of study treatment, myocardial infarction ≤ 6 months prior to the start of study treatment, unstable angina, congestive heart failure of NYHA (New York Heart Association Functional Classification) grade 2 or higher, or severe cardiac arrhythmia not controlled by drug therapy or which may interfere with study treatment
26. Significant vascular disease (e.g. aortic aneurysm requiring surgery or arterial thrombosis) within 6 months prior to initiation of study treatment
27. Venous thromboembolic disease within 3 months prior to initiation of study treatment
28. History of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to start of study treatment
29. Unhealing decaying wound, active ulcer, or untreated bone fracture
30. Proteinuria ≥ 2+ by urine dipstick unless a 24-hour urine protein < 1 g of protein is demonstrated
31. Lack of effective contraception in patients (male and/or female) at risk of reproduction, pregnant or breastfeeding women and women at risk of reproduction who have not had a pregnancy test. (Women of childbearing potential should agree to use a method of contraception during treatment of the trial and at least 4 months after discontinuation of oxaliplatin, 5 months after discontinuation of atezolizumab, and 6 months after discontinuation of bevacizumab. Men must agree to use a method of contraception during treatment and at least 6 months after discontinuation of oxaliplatin).
32. Persons deprived of freedom or under guardianship
33. Inability to undergo medical follow-up of the study for geographical, social or psychological reasons

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the main objective of this study is to evaluate the progression-free survival at 9 months (accoridng to RECIST 1.1) according to the investigator

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation Franc.Cancerologie Digestive

Sponsor organisation

Fondation Franc.Cancerologie Digestive

Address

7 Boulevard Jeanne D Arc

City

Dijon

Postcode

21000

Country

France

Scientific contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

david TOUGERON

Public contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

david TOUGERON

Locations

1 EU/EEA country · 24 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 15 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