Health Condition 1: C140- Malignant neoplasm of pharynx, unspecified
Conditions
Interventions
Intervention1: Capecitabine: Oral fluoropyrimidine prodrug of 5-FU
it is Converted in vivo to 5-fluorouracil (5-FU), which inhibits DNA synthesis by blocking thymidylate synthase, leading to tumor cell death. Administered orally in metronomic dosing as part of combin
it is Converted in the liver to active metabolites that alkylate DNA, causing cross-linking of DNA strands and inhibition of cell replication, leading to tumor cell death.Administered in metronomic do
it Inhibits dihydrofolate reductase (DHFR), leading to reduced tetrahydrofolate levels and inhibition of DNA, RNA, and protein synthesis, resulting in tumor cell death. Administered orally or intraven
it is Incorporated into DNA during replication, leading to chain termination
also inhibits ribonucleotide reductase, resulting in inhibition of DNA synthesis and tumor cell death. Aministered intravenously as per standard of care. Dose modifications allowed based on toxicity.
it Binds to EGFR on tumor cells, blocking ligand binding and receptor
Sponsors
Tata Memorial Centre
Eligibility
Inclusion criteria
Inclusion criteria: Subjects must have histologically or cytologically confirmed squamous cell carcinoma of the head and neck (except nasopharynx). Patients must have recurrent or metastatic disease, and must not be amenable to curative intent therapy. Male, female, or transgender subjects aged 18 years and over. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2. Subjects must have normal organ and marrow function as defined below: Hematologic: Absolute neutrophil count (ANC) greater than or equal to 1.0 into 10 power 9 per liter, platelet count greater than or equal to 100 into 10 power 9 per liter, and haemoglobin greater than or equal to 8 grams per deciliter. Hepatic: Total bilirubin level less than or equal to 1.5 times the upper limit of normal (ULN) range and AST and ALT levels less than or equal to 2.5 times ULN. Renal: Estimated creatinine clearance greater than or equal to 30 milliliters per minute. Patients with HIV are potentially eligible, as long as they have a CD4 count greater than 200, are on concurrent HAART (highly active antiretroviral therapy), and absence of active AIDS defining conditions. Women of childbearing potential must have a negative pregnancy test prior to randomization and agree to use highly effective contraception during treatment and for 6 months after last dose. Men must agree to use contraception and not father a child during treatment and for 6 months after last dose. Patients must have at least one measurable disease as per RECIST version 1.1. Ability to take oral medications. Ability to understand and the willingness to sign a written informed consent document. Willing to comply with all study requirements and procedures. For subjects of Cohort A: Documented prior exposure to a PD-1 or PD-L1 inhibitor in the palliative or metastatic setting, or relapse or progression within 3 months after completion of immunotherapy administered in the curative (definitive) setting (for example, concurrent or adjuvant). For subjects of Cohort B: No prior exposure to PD-1 or PD-L1 inhibitors in the palliative or metastatic setting, or relapse or progression greater than 3 months after completion of immunotherapy administered in the curative setting. Patients must have received at least one prior line of systemic therapy for recurrent or metastatic disease (chemotherapy, targeted therapy, or cetuximab).
Exclusion criteria
Exclusion criteria: Subjects who are receiving any other concurrent investigational agents. Prior progression on, or discontinuation due to intolerance of capecitabine and or cyclophosphamide when given in a comparable schedule. Symptomatic, uncontrolled central nervous system metastases. Patients with treated, stable central nervous system metastasis may be eligible if off steroids and neurologically stable for greater than or equal to 4 weeks. Infections: Active infection requiring systemic therapy. Hepatitis: Hepatitis B virus or hepatitis C virus infection at screening. This includes positive hepatitis B surface antigen with raised hepatitis B virus DNA or positive anti hepatitis C virus antibody with raised hepatitis C virus RNA. Mere presence of hepatitis B virus or hepatitis C virus at screening test will not rule the patient out. Hypersensitivity to study drug: Known prior severe hypersensitivity to investigational product or any component in its formulations. Cardiovascular disease: Clinically significant, that is active, cardiovascular disease, unstable angina, congestive heart failure greater than or equal to New York Heart Association Classification Class II or more, or serious uncontrolled cardiac arrhythmia. Other severe acute or chronic medical conditions including inflammatory bowel disease, pneumonitis, chronic kidney disease, known peripheral neuropathy greater than grade 1 as per CTCAE version 5.0, chronic liver disease, pulmonary fibrosis, or psychiatric conditions including recent within the past one year or active suicidal ideation or behaviour. Prior malignancy active within the last 3 years except non melanoma skin cancer or in situ cervical carcinoma unless disease is considered cured and relapse is unlikely. Active, known autoimmune disease requiring systemic immunosuppressive treatment greater than or equal to 10 milligrams prednisone equivalent daily or other immunosuppressant within 14 days prior to randomization. Replacement therapy for hypothyroidism and similar conditions is allowed. Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase II: Compare PFS between OMCT and physician s choice therapy in each cohort. Phase III: Compare OS between the two arms in each cohort.Timepoint: At patients every visit | — |
Secondary
| Measure | Time frame |
|---|---|
| To compare the overall response rate (ORR) and Disease Control Rate (DCR) according to the Response Evaluation Criteria in Solid Tumours(RECIST) version 1.1Timepoint: Assessed from date of randomization up to 24 months of follow up.;To compare the quality of life (QOL)Timepoint: Assessed at baseline and at regular intervals during treatment and follow up up to 24 months.;To assess and compare the safety and tolerabilityTimepoint: Assessed from initiation of treatment until 30 days after last dose and throughout follow up up to 24 months.;To evaluate patterns of treatment failureTimepoint: Assessed from date of randomization up to 24 months of follow up.;To assess cost-effectivenessTimepoint: NIL | — |
Countries
India
Contacts
Public ContactDr Minit Shah
Tata Memorial Hospital
Outcome results
None listed