Health Condition 1: C148- Malignant neoplasm of overlappingsites of lip, oral cavity and pharynx
Conditions
Interventions
Intervention1: Triple metronomic chemotherapy with low dose nivolumab: Patients allotted to the intervention arm will receive triple metronomic chemotherapy with low dose nivolumab . TMC will consist
Sponsors
Tata Memorial Centre
Eligibility
Inclusion criteria
Inclusion criteria: 1 Subjects must have head and neck squamous cell carcinoma and must be planned for palliative systemic therapy in the first line. 2 Patients who have received prior platinum chemotherapy in the definitive setting will be eligible as long as the disease has relapsed 6 months or beyond the time that they had received platinum therapy. Age more than 18 years. Eastern Cooperative Oncology Group ECOG performance status PS 0 2 3 Subjects must have normal organ and marrow function 4 Patients with HIV are potentially eligible as long as they have a CD4 count more than and equal to 200 are on concurrent HAART highly active antiretroviral therapy, and absence of active AIDS defining conditions. 5 Pregnancy test Negative serum or urine pregnancy test at screening for women of childbearing potential. 6 Contraception Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last nivolumab treatment administration if the risk of conception exists. Nivolumab is teratogenic to the developing human fetus.Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician immediately. Willing and able to comply with all study requirements, including treatment, able to be followed up at regular intervals and or nature of required assessments. 7Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
Exclusion criteria: 1. Subjects who are receiving any other current investigational agents. 2. IMMUNOSUPPRESSANTS Current use of immunosuppressive medication EXCEPT for the following a. intranasal, inhaled, topical steroids, or local steroid injection b. Systemic corticosteroids at physiologic doses more than and equal to 10 mg per day of prednisone or equivalent c. Steroids as premedication for hypersensitivity reactions d. Steroids for raised intracranial pressure due to the disease itself e, Steroid use for avoidance or treatment of emesis. 3. AUTOIMMUNE DISEASE 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. 4. ORGAN TRANSPLANTATION Prior organ transplantation including allogeneic stem cell transplantation. 5. INFECTIONS Active uncontrolled infection requiring systemic therapy. 6. VACCINATION Vaccination with live viral vaccine within 4 weeks of the first dose of nivolumab and while on studyis prohibited except for administration of inactivated vaccines. 7. HYPERSENSITIVITY TO STUDY DRUG Known prior severe hypersensitivity to platinum, paclitaxel, oral metronomic chemotherapy, or nivolumab or any component in their formulations, including known severehypersensitivity reactions to monoclonal antibodies 8. CARDIOVASCULAR DISEASE: Clinically significant 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, or serious cardiac arrhythmia requiring medication. 9. OTHER PERSISTING TOXICITIES Persisting toxicity related to prior therapy; however, alopecia, sensory neuropathy Grade 2, or other Grade 2 not constituting a safety risk based on Investigator’s judgment is acceptable. 10. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent 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. 11. Pregnant women are excluded from this study. Based on its mechanism of action. nivolumab can cause foetal harm when administered to a pregnant woman. Therefore, potential risks of administering nivolumab during pregnancy include increased rates of abortion or stillbirth. Women of reproductive potential will be advised to use effective contraception during treatment and for at least one month after the last dose of nivolumab. 12. Lactating women There is no information regarding the presence of nivolumab in human milk, the effects on the breastfed infant, or the effects on milk production. Since many drugs are excreted in human milk, it is advised that a lactating woman should not breastfeed during treatment and for at least one month after the last dose of nivolumab due to the potential for serious adverse
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess if TMCI results in a non-inferior OS as compared to platinum-based combination chemotherapy in patients with advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative settingTimepoint: till 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary 1 To assess if TMCI leads to superior OS as compared to platinum-based combination chemotherapy in advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting 2 To compare the PFS from TMCI as compared to platinum- based combination chemotherapy in advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting 3 To compare the response rate of TMCI as compared to platinum- based combination chemotherapy in advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting 4 To compare the QOL of patients treated with TMCI as compared to platinum- based combination chemotherapy in advanced unresectable or metastatic HNSCC that is platinum-sensitive in the first line palliative setting Tertiary To evaluate molecular parameters Timepoint: 1 Till 5 years 2 Till 5 years 3 Every 2-3 months till progression 4 at baseline and at two monthly intervals for the first 6 months Tertiary Blood 10 ml will be collected at baseline, at the time of disease response evaluation& at the disease progression. | — |
Countries
India
Contacts
Public ContactDr Vanita Noronha
Tata Memorial centre
Outcome results
None listed