Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients With Metastatic Cancer in Response After 6 Months of Standard IO — MOIO  

Hepatocellular Carcinoma Clinical Trial

Official title: Randomized Phase III Trial of Standard Immunotherapy (IO) by Checkpoint Inhibitors, Versus Reduced Dose Intensity of IO in Patients With Metastatic Cancer in Response After 6 Months of Standard IO

Status Recruiting

Clinical Trial Summary

Immunotherapy (IO), such as treatment with anti-PD-1, PD-L1, or CTLA-4 inhibitors, is a rapidly expanding treatment for multiple metastatic cancers with improved survival for certain cancers. However, the optimal duration of immunotherapies is currently unknown. Our hypothesis is that a reduced dose intensity of IO could be as effective as the current standard treatment in term of prevention of the disease progression. If proved right, this study will have a positive medico-economic impact by reduction of the costs associated with the treatment and the toxicity, and an increase of the patients' quality of life.

Clinical Trial Description

Immunotherapy (IO) is a rapidly expanding treatment for multiple metastatic cancers with improved survival for certain cancers. For currently approved immunotherapies such as PD-1 / PD-L1 inhibitors and anti-CTLA-4, the rhythm and duration of treatment are recommended until disease progression or unacceptable toxicity. However, the optimal duration of these treatments is currently unknown.

No major dose-dependent effect of anti-PD-1 have been observed and whether the frequency of infusion of IO could improve response or maintain efficacy. Moreover, phase I studies have shown that saturation of the target (PD-1 or PD-L1) can persist far beyond the serum half-life of the IO and 3-monthly infusions of an anti-PD-1 antibody could potentially generate the same level of activity as infusions administered every 2 weeks.

In silico modeling studies have suggested that alternate scheduling with IO couldn't compromise the efficacy of the treatment. Indeed, prolonged half-lives of IO drugs, time-varying clearance plus plasma concentrations far above the threshold associated with maximal target-engagement, suggest that the rhythm of administration of IO could be slowed down.

Without substantial international data for responding patients, apart metastatic melanoma in complete response, patients and physicians are afraid of stopping treatment, by fear of relapse. Over-treatment with IO may be toxic and inefficient. The rising cost of cancer care in the era of immunotherapy is of great concern for public and private payers around the world.

Chronic administration has important consequences for patients and health systems, with multiple medical visits and the risk of chronic, progressive and sometimes fatal toxicities induced by immunotherapy.

This is a pragmatic and strategic study challenging the routine practice which compares for the first time in a randomized phase III study, the standard administration of IO versus the same agent administered each three months in patients with metastatic cancer in partial or complete response after 6 months of standard IO ( except melanoma in CR).

If our hypothesis of non-inferiority of PFS with a reduced dose intensity of IO is verified, this could replace standard treatment and have a positive medico-economic impact, allowing, on the one hand, a reduction of the costs associated with the treatment and the toxicity, and on the other hand, an increase of the patients' quality of life. ;

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma
• Carcinoma, Merkel Cell
• Carcinoma, Renal Cell
• Head and Neck Cancer
• Hepatocellular Carcinoma
• Lung Cancer Metastatic
• Melanoma
• Merkel Cell Carcinoma
• Neoplasm Metastasis
• Renal Cell Carcinoma
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

• NCT number: NCT05078047
• Study type: Interventional
• Source: UNICANCER
• Contact: Clotilde SIMON
• Phone: +33 (0) 1 73 79 79 11
• Email: c-simon@unicancer.fr
• Status: Recruiting
• Phase: Phase 3
• Start date: March 8, 2022
• Completion date: March 7, 2025