Methotrexate for Immune Related Arthritis or Arthralgias (IMPACT 2.1)

Inclusion Criteria

• •1. Patients who were previously on hydroxychloroquine treatment as standard of care therapy or enrolled in IMPACT 2.0 who develop recurrent grade ≥ 2 irAA, or who remain on glucocorticoids for irAA at 3 months will be eligible for this trial.
• •2. Patients must be 18 years of age, or older.
• •3. Patients must be capable of providing consent to enrolment and treatment.
• •4. Patients with a performance status of ECOG 0-2 will be eligible for enrolment.
• •5. Patients with histologically confirmed cancer receiving anti-PD1 or anti-PDL1 monoclonal antibody ICI therapy, either alone or in combination with anti-CTLA4 monoclonal antibody ICI therapy who develop CTCAEv5.0 grade ≥2 arthritis or arthralgia that has developed on, or after, ICI therapy and is felt to be treatment related (irAA).
• •6. Adequate hematologic parameters defined by the following laboratory parameters:
• •* Hgb \>100 g/L
• •* Platelets\>150 x 109/L
• •* WBC\>Lower limit of normal
• •7. Adequate hepatic and renal function defined by the following laboratory parameters:
• •* AST, ALT, bilirubin and alkaline phosphatase within normal range,
• •* Serum creatinine ≤ upper limit of institutional normal OR calculated creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault formula.
• •* Patients with an elevated bilirubin, but confirmed to have Gilbert's disease will be eligible
• •8. Women of childbearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level \> 40 mIU/mL to confirm menopause.
• •9. Patients of childbearing/reproductive potential should use highly effective birth control methods, during the study treatment period and for a period of 6 months after the last dose of study drug. A highly effective method of birth control is defined as those that result in low failure rate (i.e., less than 1% per year) when used consistently and correctly. These may include hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy and tubal ligation. Double-barrier methods may be acceptable in circumstances when highly effective methods cannot be implemented (e.g., male condom with diaphragm, male condom with cervical cap). Note: Contraceptive requirements for the oncology regiments will apply, if they are more stringent than those for this trial. Abstinence is acceptable if this is established and preferred contraception for the patient.
• •10. Female patients who are breast-feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last dose of study drug.
• •11. Male patients should agree to not donate sperm during the study and for a period of at least 6 months after last dose of study drug.
• •12. Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial.