Comparing hydroxychloroquine and prednisone for joint pain in cancer patients

A Study to Evaluate the Efficacy and Safety Hydroxychloroquine in Immune Related Arthritis or Arthralgias

This study is testing whether adding hydroxychloroquine to prednisone can help cancer patients with joint pain from their treatment feel better than using prednisone alone.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AHS Cancer Control Alberta (other)
• Drugs / interventions: prednisone
• Locations: 1 site (Edmonton, Alberta)
• Trial ID: NCT04354649 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of hydroxychloroquine combined with prednisone versus prednisone alone in treating arthritis and arthralgia caused by immune checkpoint inhibitor therapy in cancer patients. The study aims to determine if hydroxychloroquine, which has fewer side effects than prednisone, can provide better relief from joint pain and stiffness. Participants will be adults aged 18 and older who have developed significant joint symptoms related to their cancer treatment. The trial will assess the safety and efficacy of these treatment options over a specified period.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed cancer who are undergoing immune checkpoint inhibitor therapy and have developed significant arthritis or arthralgia.

Not a fit: Patients who do not have cancer or those with joint pain not related to immune checkpoint inhibitor therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a safer and more effective treatment option for cancer patients experiencing debilitating joint pain.

How similar studies have performed: While the use of hydroxychloroquine for inflammatory conditions is established, this specific approach in the context of cancer treatment-related joint pain is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Patients must be 18 years of age, or older;
2. Patients must be capable of providing consent to enrolment and treatment.
3. Patients with a performance status of ECOG 0-2 will be eligible for enrolment (see appendix A).
4. 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).
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.

Exclusion Criteria:

1. History of inflammatory arthritis, including, but not limited to: Rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, Ankylosing spondylitis or other chronic inflammatory arthritis. Note: Patients with a known history of stable osteoarthritis will not be excluded.
2. Patients with an indication for systemic immunosuppressive medications or corticosteroids. Patients with CTCAEv5.0 grade ≥2 irAE's other than irIAA (ie. colitis, pneumonitis, rash, etc) are not eligible for trial, with the exception of endocrinopathies that are being treated with hormone replacement alone and not systemic immunosuppressive medications or corticosteroids.
3. Patients weighing \< 40 kg.
4. Patients with G6PD deficiency, porphyria or psoriasis.
5. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
6. Prolonged corrected QT interval or concurrent medications that prolong QT interval.
7. Diagnosis of immunodeficiency.
8. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
9. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAEv5.0 Grade ≥ 3).
10. Other severe acute or chronic medical conditions including inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Where this trial is running

Edmonton, Alberta

• Cross Cancer Institute — Edmonton, Alberta, Canada (RECRUITING)

Study contacts

• Principal investigator: Michael Kolinsky — AHS-CCI
• Study coordinator: Michael Kolinsky

Conditions: Arthritis, Arthralgia