A Phase I/II Clinical Trial of Nivolumab in Progressive/Relapsed Pediatric Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Enrollment
- 30
- Primary Endpoint
- Event free survival
Study Overview
Brief Summary
patients with progressive/relapsed solid tumors who failed first line therapy , will be treated biweekly with the anti PD1- Nivolumab. at least one month after treatment initiation low dose cyclophosphamide will be started .
patients on trial will submit tissue and blood tests for whole exome an immune genomic signature. patients will also undergo repeated immunophenotype as part of follow up.
Detailed Description
Programmed cell death 1 (PD-1) is an inhibitory receptor that prevents immune activation. PD-1 blockade can mediate reactivation of immune mediated tumor killing leading to tumor regression . Another mechanism of tumor associated immune inactivation is elevation of rates of T regulatory cells. This process may be prevented by treatment with low dose cyclophosphamide.
Objective:
This study will evaluate safety and tolerability of the anti PD1 antibody Nivolumab combined with other immunomodulating treatments, in pediatric patients with relapsed/progressive solid tumors
Method:
Patients will be treated with IV Nivolumab 3mg/kg over 60 minutes on day 1 and 15 of each cycle of 28 days.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to 21 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Ages Eligible for Study: 12 Months and older
- •Patients must have had histologic verification of malignancy at original diagnosis or relapse
- •Eligible pathologies:
- •neuroblastoma following lack of complete response to at least two lines of therapy
- •rhabdomyosarcoma following progression after first line therapy
- •Ewing sarcoma following progression after second line of therpy
- •Osteosarcoma following progression after first line of therapy all other pathologies will be discussed with PI
- •Patients must have measurable disease
- •Patient's current disease state must be one for which there is no known curative therapy
- •Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- •Patients must have fully recovered from the acute toxic effects of all prior anti-cancer treatment
- •At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
- •At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
- •at least 56 days must have elapsed after transplant or stem cell infusion; patients with prior allogeneic transplants are not eligible
- •Blood counts recovery including ANC >= 750/mm^3 and Platelet count >= 50,000/mm^3
- •Creatinine clearance ≤ 1.5 ULN
- •liver function:Total bilirubin ≤ 2 ULN, ALT or AST ≤ 2.5 ULN (or < 5 in case of liver impairment)
- •Life expectancy of at least 4 months
- •Negative pregnancy test in women of childbearing potential
- •Use of an effective contraceptive method during the whole treatment and
- •up to 3 months after the completion of treatment in males and females
- •prior informed consent signed
Exclusion Criteria
- •Patients requiring daily systemic corticosteroids are not eligible; patients must not have received systemic corticosteroids within 7 days of enrollment on study
- •Patients who are currently receiving another investigational drug are not eligible
- •Patients who are currently receiving other anti-cancer agents are not eligible
- •Patients with a history of any grade autoimmune disorder are not eligible; asymptomatic laboratory abnormalities (e.g. antinuclear antibody [ANA], rheumatoid factor, altered thyroid function studies) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder
- •Patients with >= grade 2 hypothyroidism due to history of autoimmunity are not eligible; note: hypothyroidism due to previous irradiation on thyroidectomy will not impact eligibility
- •Patients who have an uncontrolled infection are not eligible.
- •Patients with active autoimmune disease. (any autoimmune state requiring medical treatment-including chronic medications)all immune modifying drugs should be stopped at least 7 days prior to enrollment.
Arms & Interventions
progressive/relapsed solid tumors
patient with progressive/relapsed solid tumors who failed first line therapy
Intervention: Nivolumab,low dose cyclophosphamide (Drug)
Outcomes
Primary Outcomes
Event free survival
Time Frame: 6 months
Rate of patients with stable disease/tumor response at 6 months
Overall survival
Time Frame: 6 and 12 months
Rate of patients alive at 6 months and 12 months
Secondary Outcomes
- evaluation of predictors for response(12 months)