A Study to Evaluate the Efficacy and Safety Hydroxychloroquine in Immune Related Arthritis or Arthralgias
Many people develop joint pain, stiffness and swelling due to their cancer treatment that targets the immune system. The severity of symptoms ranges from mild to debilitating and sometimes requires delaying or stopping cancer treatment. The usual plan is to discontinue cancer treatment and give relatively high doses of a medication called prednisone (a steroid, which is an anti-inflammatory medication which may suppress the immune system) with a gradual lowering of the dose over several weeks. While this can be effective, prednisone can cause a number of side effects, and it is not known if this is the best or safest treatment. Hydroxychloroquine is a medication that is often used to treat inflammatory joint pain, such as rheumatoid arthritis, has relatively few side effects when compared to prednisone, and may be effective at treating this condition. The purpose of this study is to find out whether it is better to receive hydroxychloroquine and prednisone, or prednisone alone for joint pain. To do this, some participants will get hydroxychloroquine and some will receive a placebo (a substance that looks like the study drug but does not have any active or medicinal ingredients). A placebo is used to make the results of the study more reliable. This is a double-blinded study, which means that neither participants nor the study doctor or study staff will know which group participants are allocated. After 12 weeks of study treatment, the blind will be opened and participants will be informed which treatment was given.
• Patients must be 18 years of age, or older;
• Patients must be capable of providing consent to enrolment and treatment.
• Patients with a performance status of ECOG 0-2 will be eligible for enrolment (see appendix A).
• 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).
• Adequate hepatic and renal function defined by the following laboratory parameters:
‣ AST and ALT and alkaline phosphatase ≤ 2.5x ULN,
⁃ Total bilirubin ≤ 1.5x ULN,
⁃ Serum creatinine ≤ upper limit of institutional normal OR calculated creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault formula.
• Women of child bearing 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.
• Patients of childbearing / reproductive potential should use highly effective birth control methods, during the study treatment period and for a period of 3 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 and is accepted as a local standard.
• Female patients who are breast-feeding should discontinue nursing prior to the first dose of study treatment and until 3 months after the last dose of study drug.
• Male patients should agree to not donate sperm during the study and for a period of at least 3 months after last dose of study drug.
⁃ 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.