Treatment Efficacy of Corticosteroids, Mycophenolate Mofetil and Tacrolimus in Patients With Immune Related Hepatitis

• Status: Not yet recruiting
• Trial end date: 2023-11-07
• Target enrollment: 0
• Participant gender: All

Summary

This clinical trial is to clarify and investigate the patterns of immune related hepatitis and the optimal treatment choice for patients who are refractory to steroids. The project aims to prospectively characterize the various histopathological, biochemical and phenotypical liver injury patterns induced by immune checkpoint inhibitors, and the response to treatment to corticosteroids. Furthermore, the effect of adding a second-line immunosuppressive drug, either MMF or tacrolimus in steroid refractory or steroid dependent cases will be explored and compared.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Inge Marie Svane
• Treatments: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Mycophenolic Acid; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Tacrolimus; Ursodeoxycholic Acid

Criteria

Inclusion Criteria:

• Histologically confirmed solid cancer

• Treatment with cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) or Programmed Cell Death-1 (PD-1)/Programmed Cell Death Ligand-1 (PD-L1) inhibitor or a combination of CTLA-4 plus PD-1 inhibitors within 6 months

• Abnormal liver parameters equal to ≥ grade 3 ir-hepatitis defined as; AST/ALT >5 x upper level of normal (ULN), International Normalised Ratio (INR) ≥ 2.5 x ULN, or bilirubin > 3.0 x ULN

• Age: ≥ 18 years

• Women of childbearing potential: Negative serum pregnancy test and must use effective contraception. This applies from screening and until 6 months after treatment. Birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch are all considered effective contraceptives

• Men with female partner of childbearing potential must use effective contraception from screening and until 6 months after treatment. Effective contraceptives are as described above for the female partner. In addition, documented vasectomy and sterility or double barrier contraception are considered effective contraceptives

• Signed statement of consent after receiving oral and written study information

• Willingness to participate in the planned treatment and follow-up and capable of handling toxicities.

Exclusion Criteria:

• Concomitant chemotherapy treatment or tyrosine kinases or angiogenesis inhibitors

• Concomitant immunosuppressive medication except prednisolone

• Patients with hepatocellular carcinoma

• Known hypersensitivity to one of the active drugs or excipients

• Uncontrolled infection

• Acute viral hepatitis

• Any medical condition that will interfere with patient compliance or safety

• Simultaneous treatment with other experimental drugs or other anticancer drugs

• Pregnant or breastfeeding females

• Phenylketonuria