Health Condition 1: C19- Malignant neoplasm of rectosigmoidjunction
Conditions
Interventions
Intervention1: Low dose Nivolumab (40mg): 40 mg IV in 100 ml NS over 1hr (IV line with low-protein binding 0.2 or 0.22-micron in-line filter) every 3 weekly for 6 months and then 6 weekly for next 6 m
Sponsors
Tata Memorial Centre
Eligibility
Inclusion criteria
Inclusion criteria: 1. Subjects must have metastatic colorectal cancer with an MSI High or dMMR status confirmed by IHC or PCR or NGS 2. Post adjuvant treatment, metachronous metastatic patients who would be eligible but have not received 1st line treatment in the metastatic setting, will be included in the study. 3. Patients could have received previous adjuvant chemotherapy for colorectal cancer if the earlier treatment had been completed at least 6 months before randomization 4. Male or female subjects aged more than 18 years. 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1. 6. Subjects must have normal organ and marrow function and adequate hematological, hepatic, and renal function parameters 6. Presence of at least one measurable lesion as defined by RECIST version 1.1. 7..Patients with HIV are potentially eligible, as long as they have a CD4 count greater than 200, are on concurrent HAART (highly active anti-retroviral therapy), and have an absence of active AIDS defining conditions. 8. Negative serum or urine pregnancy test at screening for women of childbearing potential. 9. Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after the last Nivolumab treatment administration if the risk of conception exists. The effects of Nivolumab on the developing human fetus are teratogenic. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. 10. Both men and women of all races and ethnic groups are eligible for this study. 11. Willing and able to comply with all study requirements, including treatment, and able to be followed up at regular intervals and or nature of required assessments. 12. Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
Exclusion criteria: 1. Patients with active brain metastases or leptomeningeal metastases 2. Previously treated patients for the metastatic CRC will not be included in the study. 3. Subjects who are receiving any other investigational agents. 4. Within 3 weeks of administration of a chemotherapeutic agent. 5. Current use of immunosuppressive medication, EXCEPT for the following a.intranasal,inhaled,topical steroids or local steroid injection(e.g.intra articular injection) b.Systemic corticosteroids at physiologic doses less than or equal to 10 mg per day of prednisone or equivalent c.Steroids as premedication for hypersensitivity reactions(e.g. CT scan premedication) d.Steroids for raised intracranial pressure due to the disease itself a steroid use for avoidance or treatment of emesis. 6. Active autoimmune disease that might deteriorate when receiving a chemotherapeutic agent. Patients with diabetes type I,vitiligo,psoriasis, or hypo or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. 7. Prior organ transplantation including allogeneic stem cell transplantation. 8. Active infection requiring systemic therapy. 9. Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening 10. Vaccination within 4 weeks of the first dose of Nivolumab and while on study is prohibited except for the administration of inactivated vaccines. 11. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade greater than or equal to 3). 12. Clinically significant (i.e. active) cardiovascular disease cerebrovascular accident or stroke (less than 6 months prior to enrollment), myocardial infarction (less than 6 months prior to enrollment), unstable angina, congestive heart failure (greater than or equal to New York Heart Association Classification Class II)or serious cardiac arrhythmia requiring medication. 13. Persisting toxicity related to prior therapy (NCI CTCAE v4.03 Grade greater than 1) however, alopecia, sensory neuropathy Grade less than or equal to 2, or other Grade less than or equal to 2 not constituting a safety risk based on Investigators judgment is acceptable. 14. Other severe acute or chronic medical conditions including immune colitis, 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. 15. Pregnant women are excluded from this study. Based on its mechanism of action. Nivolumab can cause fetal harm when administered to a pregnant woman.Therefore,potential risks of administering Nivolumab during pregnancy include increased rates of abortion or stillbirth. Advise females of reproductive potential to use effective contraception during treatment and for at least one month after the last dose of Nivolumab. 16. Lactating females There is no information regarding the presence of Nivolumab in human milk, the effects on the breastfed infant, or th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survivalTimepoint: 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| -Clinical Benefit Rate -median progression free survival -Overall survival -EORTC QLQ-C30 -Cost-effective analysisTimepoint: 4 year | — |
Countries
India
Contacts
Public ContactDr Vikas Sureshchand Ostwal
Tata Memorial Hospital
Outcome results
None listed