Antibodies, NeoplasmPhase 1/2NCT02901145
Nivolumab in Relapsed Pediatric Solid Tumors
A Phase 1/2 study testing Nivolumab,low dose cyclophosphamide in people with Antibodies, Neoplasm, run by Hadassah Medical Organization.
Trial 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 . Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Antibodies, Neoplasm
- What is being tested?
- Nivolumab,low dose cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Nov 2016to Mar 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 23Show fewer
- 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
- Pregnancy:
- 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
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Phase I/II Clinical Trial of Nivolumab in Progressive/Relapsed Pediatric Solid Tumors
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.
Read the 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.
- Dose finding phase:
- Six patients will be accrued for the first cohort and treated for 1 month
- If an adverse event >grade 2 will occur in>2 patients, study medication dose will be reduced by 25% and another cohort of 6 patients will be accrued on the reduced dose.
- Dose finding cohorts will be accrued until determination of a dose with allowed DLT
- Expansion phase
- Following dose determination patients will be accrued, to the final number of 30 patients
- Cyclophosphamide at the dose of 50 mg/dayx7days every 14 days (one week on one week off ) will be started . immunophenotype will be done every 28 days and dose of cyclophosphamide will be elevated by 25mg /day every month until highest ratio of CD8/CD25FOXP3 cells will be reached for every child
- All patients will be treated for 1 year or until imaging proven disease progression.
- Required follow up
- All patients will undergo tumor bed imaging (CT/MRI-based on tumor location) with metastatic evaluation (according to standar follow up) every 4 months
- Tumor response will be measured based on RECIST criteria
- Toxicity assessment will be done according to the CTCAE v. 4.03
- Collateral studies:
- Immunohistochemical analysis for PD1 and PDL1 will be done on pretreatment paraffin embedded tissue to estimate it's ability to predict response.
- Immune profile of peripheral blood lymphocytes including CD3+, CD4+, CD8+ FOX P3+ cells and it's correlation to objective response to therapy.
- Exome sequencing of the tumor and peripheral blood will be done for every patient.
Exome will be evaluated for driver mutations and immunologic genomic signature.
- Conditions
- Antibodies, Neoplasm
- Being tested
- Nivolumab,low dose cyclophosphamide
- Keywords
- immunotherapy,solid tumor,pediatric
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab,low dose cyclophosphamideDrug
treatment with IV Nivolumab 3mg/kg every 2 weeks . after a month-addition of low dose cyclophosphamide at a starting dose of 50 mg/kg/day x7 days every 14 days with dose adaptation based on level of Tregulatory cells on follow up immunophenotype.
| Study group | Role | What they receive |
|---|---|---|
| progressive/relapsed solid tumors | Experimental | patient with progressive/relapsed solid tumors who failed first line therapy Receives: Drug: Nivolumab,low dose cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event free survival
Rate of patients with stable disease/tumor response at 6 months
Measured: 6 months
Overall survival
Rate of patients alive at 6 months and 12 months
Measured: 6 and 12 months
Secondary outcomes (1)
evaluation of predictors for response
correlation between levels of PD1 receptor expression in the tumor and genomic signature with response
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2016 (estimated)
- Study startNov 2016
- Primary completionNov 2019 (estimated)
- Study completionMar 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Antibodies, NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02901145
- Sponsor's protocol ID
- 0506-15-HMO
- Status last verified
- Sep 2016
- First submitted
- 11 Sep 2016
- Last updated
- 15 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Clinical Trial of Nivolumab in Progressive/Relapsed Pediatric Solid Tumors
- ClinicalTrials.gov ID
- NCT02901145
- Acronym / sponsor ID
- 0506-15-HMO
- Conditions
- Antibodies, Neoplasm
- Keywords
- immunotherapy,solid tumor,pediatric
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- Nov 2016
- Primary completion
- Nov 2019 (estimated)
- Study completion
- Mar 2020 (estimated)
- First posted
- 15 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- Dose finding phase:
- Six patients will be accrued for the first cohort and treated for 1 month
- If an adverse event >grade 2 will occur in>2 patients, study medication dose will be reduced by 25% and another cohort of 6 patients will be accrued on the reduced dose.
- Dose finding cohorts will be accrued until determination of a dose with allowed DLT
- Expansion phase
- Following dose determination patients will be accrued, to the final number of 30 patients
- Cyclophosphamide at the dose of 50 mg/dayx7days every 14 days (one week on one week off ) will be started . immunophenotype will be done every 28 days and dose of cyclophosphamide will be elevated by 25mg /day every month until highest ratio of CD8/CD25FOXP3 cells will be reached for every child
- All patients will be treated for 1 year or until imaging proven disease progression.
- Required follow up
- All patients will undergo tumor bed imaging (CT/MRI-based on tumor location) with metastatic evaluation (according to standar follow up) every 4 months
- Tumor response will be measured based on RECIST criteria
- Toxicity assessment will be done according to the CTCAE v. 4.03
- Collateral studies:
- Immunohistochemical analysis for PD1 and PDL1 will be done on pretreatment paraffin embedded tissue to estimate it's ability to predict response.
- Immune profile of peripheral blood lymphocytes including CD3+, CD4+, CD8+ FOX P3+ cells and it's correlation to objective response to therapy.
- Exome sequencing of the tumor and peripheral blood will be done for every patient.
Exome will be evaluated for driver mutations and immunologic genomic signature.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| progressive/relapsed solid tumors | Experimental | Drug: Nivolumab,low dose cyclophosphamidepatient with progressive/relapsed solid tumors who failed first line therapy |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (23 listed)
- Ages Eligible for Study: 12 Months and older
- Patients must have had histologic verification of malignancy at original diagnosis or relapse
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab,low dose cyclophosphamidetreatment with IV Nivolumab 3mg/kg every 2 weeks . after a month-addition of low dose cyclophosphamide at a starting dose of 50 mg/kg/day x7 days every 14 days with dose adaptation based on level of Tregulatory cells on follow up immunophenotype. | Drug | progressive/relapsed solid tumors |
Primary outcome
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
1 secondary outcome
evaluation of predictors for response
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2016.
- Individual participant dataSharing planned: No
Related trials for Antibodies, Neoplasm
RecruitingPhase 1/2
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma
Lymphoma, Non-Hodgkin Lymphoma
Not yet recruiting
Micro Assays for HemATology Malignancies Antibody Treatment
Hematological Malignancy
RecruitingObservational study
Collection of Human Samples to Study Hairy Cell and Other Leukemias, and to Develop Recombinant Immunotoxins for Cancer Treatment
Hairy Cell Leukemia (HCL), Chronic Lymphocytic Leukemia (CLL)
RecruitingPhase 2
Detecting Tumor DNA in the Blood of HR+/HER2-low Metastatic Breast Cancer Patients to Find Candidates for T-DXd Therapy
Breast Cancer Metastatic, Breast Cancer Stage IV
RecruitingPhase 2
Non-covalent BTK Inhibitor Nemtabrutinib in Combination With the CD20 Monoclonal Antibody Rituximab for the Treatment of Marginal Zone Lymphoma
Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma, Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nivolumab,low dose cyclophosphamide in people with Antibodies, Neoplasm, run by Hadassah Medical Organization.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Iris Fried, MD (508573151, ishonet@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event free survival (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2016.