Recurrent NeuroblastomaPhase 2METRO-NB2012NCT02641314
Metronomic Treatment in Children and Adolescents With Recurrent or Progressive High Risk Neuroblastoma
A Phase 2 study testing metronomic therapy in people with Recurrent Neuroblastoma, run by University of Cologne at 8 sites in Germany.
Trial summary
Neuroblastoma is the second most frequent cause for death from cancer in childhood. Already one year after diagnosis of recurrence from high risk neuroblastoma, 75% of the patients experience further progression. Read more about this study
- Who is it for?
- Ages 2 to 20 years
- Conditions the study is for
- Recurrent Neuroblastoma
- What is being tested?
- metronomic therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 8 sitesGermany
- Study dates
- 22 Dec 2016to 29 Jun 2023
- Phase
- Phase 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 2 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Newly diagnosed recurrence or progression of high risk neuroblastoma which progressed despite previous treatment (irrespective of the number of previous relapses/progressions).
- Refractory and/or residual high-risk neuroblastoma with measurable or evaluable disease irrespective of preceding treatment (no Progression during the minimal interval as defined below)
- Age: ≥ 2 years and < 21 years
- Measurable or evaluable disease defined as
- Presence of at least one measurable (recurrent or newly progressing) neuroblastoma lesion ≥ 10 mm by magnetic resonance imaging (MRI) or computed tomography (CT) or
- Newly detected unambiguous scintigraphic (MIBG) avid bone and/or medullary lesions
Show all 16Show fewer
- presence of unambiguous bone marrow metastasis
- Minimal interval between start of trial medication and preceding anti-cancer treatment is 4 weeks after chemotherapy, 6 weeks after radiotherapy, and 12 weeks after myeloablative therapy
- Life expectancy > 3 months
- Good to moderate general condition (performance scale ≥60)
- No serious infection
- Spontaneous recovering blood counts:
- White blood cell count ≥ 1000/µL
- Neutrophil count ≥ 500/µL
- Platelet count ≥ 25 000/µL (unsupported)
- Written informed consent of parents or legal guardian and/ or patient according to age and status of psycho-intellectual development.
Who cannot join
- Minimal residual disease status (only) without unambiguous measurable or evaluable disease
- Patients unable to swallow trial medication
- Any concomitant anti-cancer treatment (e.g. other cytostatic drugs, "small molecules", antibodies, radiotherapy, surgery of tumor or metastases)
- Treatment with medication that interact with study medication that cannot be discontinued at least one week prior to the start of trial medication and for the duration of the trial
- Intake of antihypertensive drugs, e.g. calcium channel blockers
- Established hypersensitivity to the active or one of the other constituents of the trial medication
Show all 17Show fewer
- Severe medical or psychosocial conditions preventing trial participate and/or any of the following
- Peripheral neuropathy or constipation CTCAE grade 3 or 4
- Cardiac arrhythmias (sinus bradycardia for age, sinus arrhythmia as 2.-3. grade atrioventricular block)
- Pre-existing recurrent symptomatic bronchial asthma
- Diabetes mellitus (propranolol covers symptoms of hypoglycemia)
- Conditions with low blood pressure below age-dependent normal ranges
- History of gastrointestinal ulcer or perforation
- Known active hepatitis B virus (HBV), hepatitis C (HBC) virus or human immunodeficiency virus (HIV) infection
- Concomitant participation in other clinical trials with investigational drugs or with competing interventions
- Pregnancy, lactation
- Sexually active patients not willing to use highly effective contraception
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Germany8 sites
Children's University Hospital
Bonn
Marc Hoemberg
Cologne, 50924
Children's University Hospital
Essen
Children's University Hospital
Frankfurt
Children's University Hospital
Freiburg im Breisgau
Children's Hospital, Medizinische Hochschule
Hanover
Children's University Hospital
Leipzig
Dr. von Haunersches Kinderspital
München
About this study
Official title: Phase 2 Trial of Metronomic Treatment in Children and Adolescents With Recurrent or Progressive Neuroblastoma (NB)
Neuroblastoma is the second most frequent cause for death from cancer in childhood. Already one year after diagnosis of recurrence from high risk neuroblastoma, 75% of the patients experience further progression.
Metronomic therapy is targeting not only the tumor cell, but also the tumor supplying vasculature and the interactions between Tumor and immune cells. The toxicity is expected to be low due to the low (but continuous) dosing of drugs.
The study investigates the tolerance and the efficacy of a new combination of five drugs consisting of propranolol (antiangiogenetic, anti-neuroblastic), Celecoxib (modulating immune response, ant-neuroblastic), cyclophosphamide (antiangiogenetic, anti-neuroblastic), etoposide (antiangiogenetic, anti-neuroblastic), and vinblastin (antiangiogenetic, anti-neuroblastic). Vinblastin is scheduled every 14 days intravenously, all other drugs are applied daily throughout 365 days (except etoposide for 4x3 weeks). The efficacies of each of the drugs have been demonstrated in vitro and in vivo in animal studies. All drugs have been used in children for other conditions. From those experiences low toxicities and a favorable Quality of life are expected.
Read the detailed description
Neuroblastoma relapses during or after intensive therapy most likely result from the presence of primary or acquired drug resistance. Therefore, new therapeutic modalities for salvage therapies are urgently needed.
The historical Kaplan-Meier curves of 218 unselected high risk patients after the first recurrence (from CR) or after the first progression (from PR/SD) demonstrate a 1 year event free survival rate of 25.2 ± 2.9% and a 1 year overall survival rate of 42.7 ± 3.3%.
Today cancer is widely considered as a multicomponent disease. One novel strategy likely to target the complexity of tumor cells and tumor environment is metronomic scheduling of anticancer treatment or "metronomic treatment" (MT). Low doses of chemotherapeutic drugs are continuously administered to cancer patients. The higher frequency and lower dose targets distinct aspects of cancer's functionality. Effects on tumor-angiogenesis, anti-cancer immunity and tumor stroma have been shown. Additionally low-dose metronomic treatment is often combined with modern antiinflammatory or antiangiogenic drugs, which specifically interact e.g. in tumor growth or angiogenesis pathways.
The rationale of this trial is the efficacy of metronomic therapy in heavily pre-treated refractory neuroblastoma patients.This trial protocol proposes a metronomic schedule of low dose chemotherapy with cyclophosphamide, etoposide and vinblastine, in combination with propranolol, a non-selective blocker of β adrenergic receptors and celecoxib, a selective cyclooxygenase type 2 (COX-2) inhibitor.
Patients enrolled in this study may benefit for two reasons. In the palliative situation, metronomic treatment may result in disease stabilization (SD) and a significant improvement of the quality of life (QOL) of patients e.g. by the decrease of pain through the treatment. For this reason, QOL including pain module is assessed as a separate secondary objective/ outcome measure. In the case of tumor response (PR, CR), the patients may qualify for a subsequent treatment approach aiming at further disease stabilization or even a long-term benefit.
- Conditions
- Recurrent Neuroblastoma
- Being tested
- metronomic therapy
- Keywords
- Recurrent Neuroblastoma
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metronomic therapyDrug
Also called Dociton, Celebrex, Endoxan, Lastet
- Propranolol 0.5 mg/kgxd p.o. day 1,
- mg/kgxd p.o. day 2,
- mg/kgxd p.o. day 3-365 (maximum total daily dose: 120 mg) divided in 2 doses per day
- Celecoxib 400 mg/m2xd p.o.; day 1-365 (maximum total daily dose: 800 mg) divided in 2 doses per day
- Cyclophosphamide cycle 1, day1: loading dose: 500 mg/m2 intravenous 1-h-infusion, single dose day 2-365 25 mg/m2xd p.o (maximum total daily dose: 50 mg) as single daily dose
- Vinblastine 3 mg/m2xd i.v. (maximum total daily dose: 6 mg) administered day 1 and 15 (every two weeks) as single daily dose
- Etoposide 25 mg/m2xd p.o.; day 1-21 weeks 1-3, 9-11, 17-19, 25-27 (maximum total daily dose: 50 mg) as single daily dose
| Study group | Role | What they receive |
|---|---|---|
| metronomic therapy | Experimental | Treatment consists of eight alternating 28-day-cycles of propranolol, celecoxib, cyclophosphamide, vinblastine, etoposide (PCCVE) and of propranolol, celecoxib, cyclophosphamide, vinblastine (PCCV) followed by five cycles PCCV resulting in a total of 13 cycles (364 days of treatment) Receives: Drug: metronomic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
non-inferiority of EFS compared to historical control group
The primary trial objective is to demonstrate the non-inferiority of event free survival (EFS) in comparison to a historical control group. Event free survival (EFS) defined as time from start of treatment up to Progression (emerged from residual tumor, PD) or recurrence (developing from CR achieved by metronomic treatment), permanent discontinuation of treatment for unacceptable toxicity, secondary malignant neoplasm or death of any reason.
Measured: up to 12 months
Secondary outcomes (6)
disease control rate at 6 months
Disease control rate at 6 months of metronomic treatment defined as number of patients achieving overall complete response (CR), partial response (PR) or stable disease (SD) related to all treated patients.
Measured: 6 months after start of treatment
Overall survival
Overall survival defined as time from start of treatment until death of any reason or date of last information
Measured: up to 12 months
hospitalization days
Any patient stay in hospital that includes at least one night from day 1 of metronomic treatment until 30 days after the end of treatment. Overall treatment time is 12 months.
Measured: up to 395 days
number of transfusion days
The number of days with transfusion of platelets or packed red blood cells. Overall treatment time is 12 months.
Measured: up to 365 days
drop-out rate
The number and rate of patients stopping metronomic treatment during treatment period due to patients and/or parents wish. Overall treatment time is 12 months.
Measured: up to 12 months
disease control rate at 12 months
Disease control rate at 12 months of metronomic treatment defined as number of patients achieving overall complete response (CR), partial response (PR) or stable disease (SD) related to all treated patients.
Measured: 12 months after start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2015 (estimated)
- Study start22 Dec 2016
- Primary completion29 Jun 2023
- Study completion29 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Recurrent NeuroblastomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cologne
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Marc Hömberg, University of Cologne
- Investigators
- Marc Hoemberg, Dr., Principal investigator, University of Cologne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02641314
- Sponsor's protocol ID
- Uni-Koeln-1495
- Other IDs
- 2011-004593-29
- Acronym
- METRO-NB2012
- Status last verified
- May 2024
- First submitted
- 15 Dec 2015
- Last updated
- 10 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Simon T, Berthold F, Borkhardt A, Kremens B, De Carolis B, Hero B. Treatment and outcomes of patients with relapsed, high-risk neuroblastoma: results of German trials. Pediatr Blood Cancer. 2011 Apr;56(4):578-83. doi: 10.1002/pbc.22693. Epub 2010 Dec 9.
PubMed 21298742Klement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ, Bohlen P, Kerbel RS. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest. 2000 Apr;105(8):R15-24. doi: 10.1172/JCI8829.
PubMed 10772661Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother. 2007 May;56(5):641-8. doi: 10.1007/s00262-006-0225-8. Epub 2006 Sep 8.
PubMed 16960692Wang YC, He F, Feng F, Liu XW, Dong GY, Qin HY, Hu XB, Zheng MH, Liang L, Feng L, Liang YM, Han H. Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor immune responses. Cancer Res. 2010 Jun 15;70(12):4840-9. doi: 10.1158/0008-5472.CAN-10-0269. Epub 2010 May 25.
PubMed 20501839Ponthan F, Wickstrom M, Gleissman H, Fuskevag OM, Segerstrom L, Sveinbjornsson B, Redfern CP, Eksborg S, Kogner P, Johnsen JI. Celecoxib prevents neuroblastoma tumor development and potentiates the effect of chemotherapeutic drugs in vitro and in vivo. Clin Cancer Res. 2007 Feb 1;13(3):1036-44. doi: 10.1158/1078-0432.CCR-06-1908.
PubMed 17289900Nakanishi Y, Nakatsuji M, Seno H, Ishizu S, Akitake-Kawano R, Kanda K, Ueo T, Komekado H, Kawada M, Minami M, Chiba T. COX-2 inhibition alters the phenotype of tumor-associated macrophages from M2 to M1 in ApcMin/+ mouse polyps. Carcinogenesis. 2011 Sep;32(9):1333-9. doi: 10.1093/carcin/bgr128. Epub 2011 Jul 5.
PubMed 21730361Asgharzadeh S, Salo JA, Ji L, Oberthuer A, Fischer M, Berthold F, Hadjidaniel M, Liu CW, Metelitsa LS, Pique-Regi R, Wakamatsu P, Villablanca JG, Kreissman SG, Matthay KK, Shimada H, London WB, Sposto R, Seeger RC. Clinical significance of tumor-associated inflammatory cells in metastatic neuroblastoma. J Clin Oncol. 2012 Oct 1;30(28):3525-32. doi: 10.1200/JCO.2011.40.9169. Epub 2012 Aug 27.
PubMed 22927533Pasquier E, Street J, Pouchy C, Carre M, Gifford AJ, Murray J, Norris MD, Trahair T, Andre N, Kavallaris M. beta-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma. Br J Cancer. 2013 Jun 25;108(12):2485-94. doi: 10.1038/bjc.2013.205. Epub 2013 May 21.
PubMed 23695022Andre N, Carre M, Pasquier E. Metronomics: towards personalized chemotherapy? Nat Rev Clin Oncol. 2014 Jul;11(7):413-31. doi: 10.1038/nrclinonc.2014.89. Epub 2014 Jun 10.
PubMed 24913374Berthold F, Homberg M, Proleskovskaya I, Mazanek P, Belogurova M, Ernst A, Sterba J. Metronomic therapy has low toxicity and is as effective as current standard treatment for recurrent high-risk neuroblastoma. Pediatr Hematol Oncol. 2017 Aug;34(5):308-319. doi: 10.1080/08880018.2017.1373314. Epub 2017 Nov 17.
PubMed 29148865
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of Metronomic Treatment in Children and Adolescents With Recurrent or Progressive Neuroblastoma (NB)
- ClinicalTrials.gov ID
- NCT02641314
- Acronym / sponsor ID
- METRO-NB2012 / Uni-Koeln-1495
- Conditions
- Recurrent Neuroblastoma
- Keywords
- Recurrent Neuroblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of CologneUniversity, hospital or other
- Study start
- 22 Dec 2016 (actual)
- Primary completion
- 29 Jun 2023 (actual)
- Study completion
- 29 Jun 2023 (actual)
- First posted
- 29 Dec 2015 (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.
Neuroblastoma is the second most frequent cause for death from cancer in childhood. Already one year after diagnosis of recurrence from high risk neuroblastoma, 75% of the patients experience further progression.
Metronomic therapy is targeting not only the tumor cell, but also the tumor supplying vasculature and the interactions between Tumor and immune cells. The toxicity is expected to be low due to the low (but continuous) dosing of drugs.
The study investigates the tolerance and the efficacy of a new combination of five drugs consisting of propranolol (antiangiogenetic, anti-neuroblastic), Celecoxib (modulating immune response, ant-neuroblastic), cyclophosphamide (antiangiogenetic, anti-neuroblastic), etoposide (antiangiogenetic, anti-neuroblastic), and vinblastin (antiangiogenetic, anti-neuroblastic). Vinblastin is scheduled every 14 days intravenously, all other drugs are applied daily throughout 365 days (except etoposide for 4x3 weeks). The efficacies of each of the drugs have been demonstrated in vitro and in vivo in animal studies. All drugs have been used in children for other conditions. From those experiences low toxicities and a favorable Quality of life are expected.
Detailed description
Neuroblastoma relapses during or after intensive therapy most likely result from the presence of primary or acquired drug resistance. Therefore, new therapeutic modalities for salvage therapies are urgently needed.
The historical Kaplan-Meier curves of 218 unselected high risk patients after the first recurrence (from CR) or after the first progression (from PR/SD) demonstrate a 1 year event free survival rate of 25.2 ± 2.9% and a 1 year overall survival rate of 42.7 ± 3.3%.
Today cancer is widely considered as a multicomponent disease. One novel strategy likely to target the complexity of tumor cells and tumor environment is metronomic scheduling of anticancer treatment or "metronomic treatment" (MT). Low doses of chemotherapeutic drugs are continuously administered to cancer patients. The higher frequency and lower dose targets distinct aspects of cancer's functionality. Effects on tumor-angiogenesis, anti-cancer immunity and tumor stroma have been shown. Additionally low-dose metronomic treatment is often combined with modern antiinflammatory or antiangiogenic drugs, which specifically interact e.g. in tumor growth or angiogenesis pathways.
The rationale of this trial is the efficacy of metronomic therapy in heavily pre-treated refractory neuroblastoma patients.This trial protocol proposes a metronomic schedule of low dose chemotherapy with cyclophosphamide, etoposide and vinblastine, in combination with propranolol, a non-selective blocker of β adrenergic receptors and celecoxib, a selective cyclooxygenase type 2 (COX-2) inhibitor.
Patients enrolled in this study may benefit for two reasons. In the palliative situation, metronomic treatment may result in disease stabilization (SD) and a significant improvement of the quality of life (QOL) of patients e.g. by the decrease of pain through the treatment. For this reason, QOL including pain module is assessed as a separate secondary objective/ outcome measure. In the case of tumor response (PR, CR), the patients may qualify for a subsequent treatment approach aiming at further disease stabilization or even a long-term benefit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| metronomic therapy | Experimental | Drug: metronomic therapyTreatment consists of eight alternating 28-day-cycles of propranolol, celecoxib, cyclophosphamide, vinblastine, etoposide (PCCVE) and of propranolol, celecoxib, cyclophosphamide, vinblastine (PCCV) followed by five cycles PCCV resulting in a total of 13 cycles (364 days of treatment) |
Who may qualify
- Ages
- 2 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- Newly diagnosed recurrence or progression of high risk neuroblastoma which progressed despite previous treatment (irrespective of the number of previous relapses/progressions).
- Refractory and/or residual high-risk neuroblastoma with measurable or evaluable disease irrespective of preceding treatment (no Progression during the minimal interval as defined below)
- Age: ≥ 2 years and < 21 years
- Measurable or evaluable disease defined as
- Minimal interval between start of trial medication and preceding anti-cancer treatment is 4 weeks after chemotherapy, 6 weeks after radiotherapy, and 12 weeks after myeloablative therapy
Key exclusion criteria (17 listed)
- Minimal residual disease status (only) without unambiguous measurable or evaluable disease
- Patients unable to swallow trial medication
- Any concomitant anti-cancer treatment (e.g. other cytostatic drugs, "small molecules", antibodies, radiotherapy, surgery of tumor or metastases)
- Treatment with medication that interact with study medication that cannot be discontinued at least one week prior to the start of trial medication and for the duration of the trial
- Intake of antihypertensive drugs, e.g. calcium channel blockers
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 |
|---|---|---|
| metronomic therapyAlso: Dociton, Celebrex, Endoxan, Lastet* Propranolol 0.5 mg/kgxd p.o. day 1, 1. mg/kgxd p.o. day 2, 2. mg/kgxd p.o. day 3-365 (maximum total daily dose: 120 mg) divided in 2 doses per day * Celecoxib 400 mg/m2xd p.o.; day 1-365 (maximum total daily dose: 800 mg) divided in 2 doses per day * Cyclophosphamide cycle 1, day1: loading dose: 500 mg/m2 intravenous 1-h-infusion, single dose day 2-365 25 mg/m2xd p.o (maximum total daily dose: 50 mg) as single daily dose * Vinblastine 3 mg/m2xd i.v. (maximum total daily dose: 6 mg) administered day 1 and 15 (every two weeks) as single daily dose * Etoposide 25 mg/m2xd p.o.; day 1-21 weeks 1-3, 9-11, 17-19, 25-27 (maximum total daily dose: 50 mg) as single daily dose | Drug | metronomic therapy |
Primary outcome
non-inferiority of EFS compared to historical control group
Time frame: up to 12 months
The primary trial objective is to demonstrate the non-inferiority of event free survival (EFS) in comparison to a historical control group. Event free survival (EFS) defined as time from start of treatment up to Progression (emerged from residual tumor, PD) or recurrence (developing from CR achieved by metronomic treatment), permanent discontinuation of treatment for unacceptable toxicity, secondary malignant neoplasm or death of any reason.
6 secondary outcomes
disease control rate at 6 months
Time frame: 6 months after start of treatment
Overall survival
Time frame: up to 12 months
hospitalization days
Time frame: up to 395 days
number of transfusion days
Time frame: up to 365 days
drop-out rate
Time frame: up to 12 months
disease control rate at 12 months
Time frame: 12 months after start of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2024.
- Background: PubMed 21298742Simon T, Berthold F, Borkhardt A, Kremens B, De Carolis B, Hero B. Treatment and outcomes of patients with relapsed, high-risk neuroblastoma: results of German trials. Pediatr Blood Cancer. 2011 Apr;56(4):578-83. doi: 10.1002/pbc.22693. Epub 2010 Dec 9.
- Background: PubMed 10772661Klement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ, Bohlen P, Kerbel RS. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest. 2000 Apr;105(8):R15-24. doi: 10.1172/JCI8829.
- Background: PubMed 16960692Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother. 2007 May;56(5):641-8. doi: 10.1007/s00262-006-0225-8. Epub 2006 Sep 8.
- Background: PubMed 20501839Wang YC, He F, Feng F, Liu XW, Dong GY, Qin HY, Hu XB, Zheng MH, Liang L, Feng L, Liang YM, Han H. Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor immune responses. Cancer Res. 2010 Jun 15;70(12):4840-9. doi: 10.1158/0008-5472.CAN-10-0269. Epub 2010 May 25.
- Background: PubMed 17289900Ponthan F, Wickstrom M, Gleissman H, Fuskevag OM, Segerstrom L, Sveinbjornsson B, Redfern CP, Eksborg S, Kogner P, Johnsen JI. Celecoxib prevents neuroblastoma tumor development and potentiates the effect of chemotherapeutic drugs in vitro and in vivo. Clin Cancer Res. 2007 Feb 1;13(3):1036-44. doi: 10.1158/1078-0432.CCR-06-1908.
- Background: PubMed 21730361Nakanishi Y, Nakatsuji M, Seno H, Ishizu S, Akitake-Kawano R, Kanda K, Ueo T, Komekado H, Kawada M, Minami M, Chiba T. COX-2 inhibition alters the phenotype of tumor-associated macrophages from M2 to M1 in ApcMin/+ mouse polyps. Carcinogenesis. 2011 Sep;32(9):1333-9. doi: 10.1093/carcin/bgr128. Epub 2011 Jul 5.
- Background: PubMed 22927533Asgharzadeh S, Salo JA, Ji L, Oberthuer A, Fischer M, Berthold F, Hadjidaniel M, Liu CW, Metelitsa LS, Pique-Regi R, Wakamatsu P, Villablanca JG, Kreissman SG, Matthay KK, Shimada H, London WB, Sposto R, Seeger RC. Clinical significance of tumor-associated inflammatory cells in metastatic neuroblastoma. J Clin Oncol. 2012 Oct 1;30(28):3525-32. doi: 10.1200/JCO.2011.40.9169. Epub 2012 Aug 27.
- Background: PubMed 23695022Pasquier E, Street J, Pouchy C, Carre M, Gifford AJ, Murray J, Norris MD, Trahair T, Andre N, Kavallaris M. beta-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma. Br J Cancer. 2013 Jun 25;108(12):2485-94. doi: 10.1038/bjc.2013.205. Epub 2013 May 21.
- Background: PubMed 24913374Andre N, Carre M, Pasquier E. Metronomics: towards personalized chemotherapy? Nat Rev Clin Oncol. 2014 Jul;11(7):413-31. doi: 10.1038/nrclinonc.2014.89. Epub 2014 Jun 10.
- Background: PubMed 29148865Berthold F, Homberg M, Proleskovskaya I, Mazanek P, Belogurova M, Ernst A, Sterba J. Metronomic therapy has low toxicity and is as effective as current standard treatment for recurrent high-risk neuroblastoma. Pediatr Hematol Oncol. 2017 Aug;34(5):308-319. doi: 10.1080/08880018.2017.1373314. Epub 2017 Nov 17.
- Individual participant dataSharing planned: No
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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.
Marc Hoemberg, Dr. principal investigator
University of Cologne
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing metronomic therapy in people with Recurrent Neuroblastoma, run by University of Cologne at 8 sites in Germany.
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 16 inclusion and 17 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: finished, as of the sponsor's last update on 10 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
non-inferiority of EFS compared to historical control group (time frame: up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02641314, which also lists 10 linked publications.
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 10 May 2024.