Methotrexate for Immune Related Arthritis or Arthralgias (IMPACT 2.1)

Launched by AHS CANCER CONTROL ALBERTA · Aug 18, 2023

Keywords

ClinConnect Summary

The IMPACT 2.1 trial is studying how well a medication called methotrexate can help people who experience joint pain and stiffness due to cancer treatments that affect the immune system. Many patients undergoing these treatments develop this inflammation, which can be painful and may sometimes require them to pause or stop their cancer therapy. This study aims to find out if methotrexate is a better and safer option than the usual treatment, which often involves using a steroid called prednisone that can have unwanted side effects.

To participate in this trial, individuals must be at least 18 years old and have already tried another medication, hydroxychloroquine, for their joint pain but did not have a good response. Participants should also be receiving certain types of cancer treatment, specifically those involving immune-based therapies. If eligible, patients can expect close monitoring and support from the research team while they receive methotrexate. This trial is important as it seeks to improve treatment options for those suffering from joint pain linked to cancer therapies, potentially leading to better management of their symptoms and allowing them to continue their cancer treatment more comfortably.

Gender

ALL

Eligibility criteria

• 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 and is accepted as a local standard.
• • 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.
• 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 irAA (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 with G6PD deficiency, porphyria or psoriasis.
• • 4. 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.
• • 5. Diagnosis of immunodeficiency.
• • 6. Diagnosis of untreated hepatitis B and C.
• • 7. Current use of immunosuppressive medication, EXCEPT for the following: prednisone and hydroxychloroquine per IMPACT 2.0 protocol or standard of care.
• • 8. 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).
• • 9. Excessive alcohol intake defined as greater than 7 units per week.
• • 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 (see parameters in inclusion criteria) 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.