Health Condition 1: C15-C26- Malignant neoplasms of digestive organs Health Condition 2: C50-C50- Malignant neoplasms of breast Health Condition 3: C30-C39- Malignant neoplasms of respiratory and intrathoracic organs Health Condition 4: C00-C14- Malignant neoplasms of lip, oral cavity and pharynx Health Condition 5: C64-C68- Malignant neoplasms of urinary tract
Conditions
Interventions
Intervention1: not applicable: not applicable
Intervention2: Toripalimab: aToripalimab is a monoclonal antibody that acts as a programmed death receptor-1 (PD-1) blocking antibody. Its mechanism of ac
Sponsors
Tata Memorial Hospital
Eligibility
Inclusion criteria
Inclusion criteria: Diagnosis Histologically confirmed incurable advanced (metastatic and or unresectable) MSI H or dMMR solid tumor, excluding colorectal cancer. a. MSI H or dMMR status confirmed by immunohistochemistry, polymerase chain reaction, or next generation sequencing. If diagnosed by immunohistochemistry with single protein loss, confirmation by polymerase chain reaction is required. b. Patients with metachronous metastatic disease following adjuvant therapy who have not received first line treatment in the metastatic setting are eligible, provided: Adjuvant chemotherapy, including monoclonal antibodies if any, was completed at least six months prior to screening and randomization Prior immune checkpoint inhibitors used in the adjuvant or neoadjuvant setting were completed at least twelve months prior c. Patients who have received up to one cycle of systemic therapy, including chemotherapy, targeted therapy, or immune checkpoint inhibitors, alone or in combination, while awaiting MSI or MMR results are eligible. Age Eighteen years or older at the time of consent. Performance Status Eastern Cooperative Oncology Group performance status zero to two. Adequate Organ and Marrow Function a. Hematologic: Absolute neutrophil count at least one point five multiplied by ten to the power of nine per liter Platelet count at least one hundred multiplied by ten to the power of nine per liter Hemoglobin at least eight grams per deciliter, transfusions permitted b. Hepatic: Total bilirubin no more than one point five times the upper limit of normal Aspartate aminotransferase and alanine aminotransferase no more than five times the upper limit of normal c. Renal: Estimated creatinine clearance at least forty milliliters per minute using the Cockcroft Gault formula or equivalent method Pregnancy Test Negative serum or urine pregnancy test at screening for women of childbearing potential. Contraception Use of highly effective contraception by male and female participants throughout the study and for at least thirty days after the last dose of toripalimab, if there is a risk of conception. Participants must inform the investigator immediately if pregnancy occurs or is suspected. Compliance Willingness and ability to comply with study treatment, scheduled follow up visits, and required assessments. Informed Consent Ability to understand and willingness to provide written informed consent.
Exclusion criteria
Exclusion criteria: Active brain metastases or leptomeningeal disease. Current use of immunosuppressive therapy, except: Intranasal, inhaled, topical, or local steroid injections Physiologic systemic corticosteroids at doses up to ten milligrams per day of prednisone or equivalent Steroids used as premedication for hypersensitivity reactions Steroids used for disease related raised intracranial pressure Steroids used for prevention or treatment of emesis Active autoimmune disease likely to worsen with therapy. Patients with Type One diabetes, vitiligo, psoriasis, or controlled hypo or hyperthyroidism not requiring immunosuppression are eligible. History of organ transplantation, including allogeneic stem cell transplantation. Active infection requiring systemic treatment. Active hepatitis B or hepatitis C infection at screening. Patients receiving appropriate antiviral therapy for at least four weeks may be considered on a case by case basis. Receipt of any vaccination within four weeks prior to the first dose or during the study, except inactivated vaccines. Prior severe hypersensitivity to the study drug or its components, including Grade three or higher reactions to immune checkpoint inhibitors as per NCI CTCAE version four point zero three. Uncontrolled significant comorbidities, such as severe congestive heart failure or coronary artery disease. Persistent toxicity from prior anticancer therapy of more than Grade one as per NCI CTCAE version four point zero three, except alopecia, Grade two or lower sensory neuropathy, or other Grade two or lower toxicities deemed acceptable by the Investigator. Other severe acute or uncontrolled chronic medical or psychiatric conditions, including immune mediated colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis, or recent or active suicidal ideation, or clinically significant laboratory abnormalities that may increase risk or interfere with study outcomes. Pregnancy. Women of reproductive potential must use effective contraception during treatment and for at least one month after the last dose. Lactation. Breastfeeding is prohibited during treatment and for at least one month after the last dose. Colorectal cancer patients at TMH Mumbai during the initial study phase due to a competing nivolumab trial. Other centers may recruit such patients, and TMH may do so after completion of the competing study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective would be achievement of a 2-year PFS of at least 40% in all enrolled patientsTimepoint: To evaluate 2-year progression-free survival (PFS), defined as the proportion of patients who are alive and progression-free 24 months from study entry (randomization/enrollment). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall Survival 2. Incidence of adverse events, including IRAE 3. Quality of life Timepoint: Overall Survival (OS): To assess overall survival, defined as the time from diagnosis of advanced disease until death from any cause, with patients who are alive censored at the date they were last known to be alive. Adverse Events (AEs): To evaluate the safety of Toripalimab by assessing treatment-emergent adverse events occurring from the first dose of study drug until 30 days after the last dose, graded according to NCI-CTCAE version 5.0. Quality of Life (QOL): To assess quality of life using the EORTC QLQ-C30 questionnaire, measured at baseline and at 6-monthly intervals for up to 24 months while on study, with assessments discontinued after disease progression. | — |
Countries
India
Contacts
Public ContactDr Anuradha Mehta
Tata Memorial Hospital
Outcome results
None listed