Study to Evaluate Efficacy and Safety of Selective Internal Radiation Therapy Plus Xelox, Bevacizumab and Atezolizumab (Immune Chekpoint Inhibitor) in Patients With Liver-dominant Metastatic Colorectal Cancer

NCT04659382 | Unknown Phase 2

• 1 other identifier: FFCD1709-SIRTCI
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 19

Brief Summary

The main objective of the SIRTCI study is to evaluate the safety and efficacy of the combination chemotherapy (XELOX: Capecitabine plus oxaliplatin), anti-angiogenic (Bevacizumab), SIRT (TheraSphere®) and ICI (Atezolizumab) in patients with CRC with predominant liver metastases. SIRTCI is a single-arm, prospective, multi-centre phase II study. The main inclusion criteria are patients with MSS mRCC with predominantly non-operable liver metastases and measurable disease. Patients with extra-hepatic metastases can be included since the objective of the study is to induce local and abscopal effects of radiotherapy combined with ICI by stimulating the anti-tumour immune response to destroy both hepatic and extra-hepatic metastases.

Conditions

Metastatic Colorectal Cancer; pMMR; MSS; Immune Checkpoint Inhibitor; Internal Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 9 months

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

  9 months after inclusion of the last patient

Study Arms (1)

Single arm

EXPERIMENTAL

XELOX + bevacizumab + atezolizumab + SIRT (Therasphere)

Drug: Atezolizumab; Device: Therasphere; Drug: XELOX; Drug: Bevacizumab

Interventions

Atezolizumab DRUG

Atezolizumab combined to standard chemotherapy (XELOX + bevacizumab) and targeted therapy in patients whose tumour has been made immunogenic by radiotherapy (Therasphere) and ICI (atezolizumab).

Single arm

Therasphere DEVICE

Therasphere injected to patients to promote the release of neoantigens from their tumour and convert it into an immunogenic tumour.

Single arm

XELOX DRUG

standard chemotherapy for first line treament of metastatic CRC (in pMMR and/or MSS patients)

Single arm

Bevacizumab DRUG

standard targeted therapy associated with XELOX for first line treament of metastatic CRC (in pMMR and/or MSS patients)

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Histologically proven mismatch repair proficient metastatic colorectal cancer (pMMR and/or MSS)
• Liver-dominant disease with up to 6 extrahepatic lesions (only peritoneal lesions are not allowed) if asymptomatic and without organ dysfunction.
• Measurable disease according to RECIST 1.1
• Patient with initially unresectable disease according to the local multidisciplinary team and eligible for radioembolization according to the radiologist's opinion
• Tumor volume \< 50 % of total liver volume
• WHO performance status ≤ 1
• Estimated life expectancy ≥ 3 months
• Adequate hematological function: with neutrophils ≥ 1,500 /mm3, platelet count ≥ 100,000/mm3, hemoglobin \> 9 g/dL (5,6 mmol/l)
• Adequate hepatic function: hepatic transaminases (ASAT and ALAT) ≤ 5 x UNL, total bilirubin ≤ 2 x UNL, alkaline phosphatase ≤ 5 x UNL
• Adequate renal function: creatinine clearance ≥ 50 ml/min according MDRD (Modification of Diet in Renal Disease)
• Patient affiliated to a social security system Information provided to patient and signature of the informed consent form by patient and the investigator

You may not qualify if:

• Active infection still requiring intravenous antibiotics on the first scheduled day of protocol treatment
• Symptomatic or untreated central nervous system metastasis
• 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,
• Confirmed peritoneal carcinomatosis (lesions detectable on CT-scan and/or MRI)
• Active autoimmune disease or inflammatory bowel disease
• Bone marrow allograft or solid organ transplant history
• 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
• Positive tests for HIV or other immunodeficiency syndromes
• Severe chronic liver failure, which in the investigator's opinion would not allow SIRT to be received safely
• Active hepatitis B or hepatitis C.
• Active tuberculosis
• 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.
• 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)
• If primary tumor is non-resected, it must be asymptomatic
• 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)

Sponsors & Collaborators

• Federation Francophone de Cancerologie Digestive: lead

Study Sites (19)

Chu - Hôpital Sud

Amiens, France

ACTIVE NOT RECRUITING

Privé - Cac - Clinique Bergonié

Bordeaux, France

ACTIVE NOT RECRUITING

Chu - Hôpital Henri Mondor

Créteil, France

ACTIVE NOT RECRUITING

Chu - Hôpital François Mitterrand

Dijon, France

ACTIVE NOT RECRUITING

Privé - Cac - Centre Georges François Leclerc

Dijon, France

ACTIVE NOT RECRUITING

Chu - Hôpital Grenoble Alpes

Grenoble, France

ACTIVE NOT RECRUITING

Chu - Hôpital Edouard Herriot

Lyon, France

ACTIVE NOT RECRUITING

Chu - Hôpital La Timone

Marseille, France

ACTIVE NOT RECRUITING

Privé - Cac - Institut Paoli Calmettes

Marseille, France

ACTIVE NOT RECRUITING

Chu - Hôpital Saint Éloi

Montpellier, France

ACTIVE NOT RECRUITING

Chu - Hôpital Européen Georges Pompidou

Paris, France

ACTIVE NOT RECRUITING

Chu - Hôpital Saint Louis

Paris, France

ACTIVE NOT RECRUITING

Chu - Hôpital Haut Lévêque

Pessac, France

ACTIVE NOT RECRUITING

Chu - Hôpital Lyon Sud

Pierre-Bénite, France

ACTIVE NOT RECRUITING

Chu - Hôpital La Milétrie

Poitiers, 86021, France

RECRUITING

Privé - Cac - Centre Eugène Marquis

Rennes, France

ACTIVE NOT RECRUITING

Chu - Hôpital Charles Nicolle

Rouen, France

ACTIVE NOT RECRUITING

Privé - Cac - Centre Henri Becquerel

Rouen, France

ACTIVE NOT RECRUITING

Chu - Hôpital Hautepierre

Strasbourg, France

ACTIVE NOT RECRUITING

Related Publications (7)

• Wasan HS, Gibbs P, Sharma NK, Taieb J, Heinemann V, Ricke J, Peeters M, Findlay M, Weaver A, Mills J, Wilson C, Adams R, Francis A, Moschandreas J, Virdee PS, Dutton P, Love S, Gebski V, Gray A; FOXFIRE trial investigators; SIRFLOX trial investigators; FOXFIRE-Global trial investigators; van Hazel G, Sharma RA. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol. 2017 Sep;18(9):1159-1171. doi: 10.1016/S1470-2045(17)30457-6. Epub 2017 Aug 3.

  PMID: 28781171 BACKGROUND

• Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, Berry S, Polite BN, O'Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB 3rd, Mulkerin DL, Mayer RJ, Blanke C. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017 Jun 20;317(23):2392-2401. doi: 10.1001/jama.2017.7105.

  PMID: 28632865 BACKGROUND

• Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmuller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Hielscher J, Scholz M, Muller S, Link H, Niederle N, Rost A, Hoffkes HG, Moehler M, Lindig RU, Modest DP, Rossius L, Kirchner T, Jung A, Stintzing S. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Sep;15(10):1065-75. doi: 10.1016/S1470-2045(14)70330-4. Epub 2014 Jul 31.

  PMID: 25088940 BACKGROUND

• Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Cassidy J. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008 Apr 20;26(12):2013-9. doi: 10.1200/JCO.2007.14.9930.

  PMID: 18421054 BACKGROUND

• Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, Cortesi E, Tomasello G, Ronzoni M, Spadi R, Zaniboni A, Tonini G, Buonadonna A, Amoroso D, Chiara S, Carlomagno C, Boni C, Allegrini G, Boni L, Falcone A. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014 Oct 23;371(17):1609-18. doi: 10.1056/NEJMoa1403108.

  PMID: 25337750 BACKGROUND

• van Hazel GA, Heinemann V, Sharma NK, Findlay MP, Ricke J, Peeters M, Perez D, Robinson BA, Strickland AH, Ferguson T, Rodriguez J, Kroning H, Wolf I, Ganju V, Walpole E, Boucher E, Tichler T, Shacham-Shmueli E, Powell A, Eliadis P, Isaacs R, Price D, Moeslein F, Taieb J, Bower G, Gebski V, Van Buskirk M, Cade DN, Thurston K, Gibbs P. SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer. J Clin Oncol. 2016 May 20;34(15):1723-31. doi: 10.1200/JCO.2015.66.1181. Epub 2016 Feb 22.

  PMID: 26903575 BACKGROUND

• Gruenberger T, Bridgewater J, Chau I, Garcia Alfonso P, Rivoire M, Mudan S, Lasserre S, Hermann F, Waterkamp D, Adam R. Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol. 2015 Apr;26(4):702-708. doi: 10.1093/annonc/mdu580. Epub 2014 Dec 23.

  PMID: 25538173 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

atezolizumab; XELOX; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

David Tougeron, MD, PhD

CONTACT

0380393404; david.tougeron@chu-poitiers.fr

Flore Geillon, PhD

CONTACT

flore.geillon@u-bourgogne.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: December 9, 2020
• Study Start: October 7, 2020
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: August 18, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (19)