Pediatric High Risk GliomasPhase 2NCT01574092
Irinotecan in Combination With Cisplatin in Pediatric Patients With Unfavorable Prognosis Gliomas
A Phase 2 study testing Combination of two marketed drugs (irinotecan and cisplatin) in people with Pediatric High Risk Gliomas, run by Hospital Sant Joan de Deu at 1 site in Spain.
Trial summary
Tumours of the brain and of the central nervous system (CNS) are the most common solid tumours in children. Amongst these, gliomas are the most frequent, although this term covers different histological subtypes, the most frequent being astrocytoma. However, they are rare diseases of low prevalence. Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- Pediatric High Risk Gliomas
- What is being tested?
- Combination of two marketed drugs (irinotecan and cisplatin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteSpain
- Study dates
- Nov 2009to Mar 2015
- 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 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histological confirmation of neoplasia, except for intrinsic brain stem tumour and optic pathway glioma in one patient with neurofibromatosis type 1 (NF1).
- Pertaining to one of the diagnostic groups: Cohort 1: Recently diagnosed high grade glioma. Cohort 2: Recurrent high grade glioma. Cohort 3: Intrinsic brain stem tumour. Cohort 4: High risk low grade glioma.
- Measurable primary or metastatic tumours with at least one 10 mm diameter lesion in two MR dimensions.
- Absence of prior treatment with cisplatin or irinotecan.
- Aged between 6 months to 18 years.
- Lansky/Karnofsky performance status ≥ 70% (Appendix 6.1). Neurological deficits secondary to the tumour should be stable before entering the trial.
Show all 12Show fewer
- Patients receiving dexamethasone should be on a stable or decreasing regimen before inclusion.
- Life expectancy ≥ 3 months.
- Adequate organic function, including haematological, renal and hepatic function.
- Wash-out period of at least 3 weeks after chemotherapy and 6 weeks after nitrosoureas or radiotherapy. Recovery from all toxic effects of previous treatments.
- Subjects of fertile age should use an effective birth control method throughout the entire study. Women of child-bearing age will be included after a negative pregnancy test result.
- Informed consent of the parents or legal representative, and informed consent of the mature minor.
Who cannot join
- Concurrent administration of any other anti-cancer treatment.
- Pre-existing, non-controlled diarrhoea
- Pregnancy or lactation
- Treatment in another clinical trial.
- Serious concomitant disease that could compromise the completion of the trial. -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II, Single Arm, Open Label Clinical Trial With Irinotecan in Combination With Cisplatin in Pediatric Patients With Unfavorable Prognosis Gliomas
Tumours of the brain and of the central nervous system (CNS) are the most common solid tumours in children. Amongst these, gliomas are the most frequent, although this term covers different histological subtypes, the most frequent being astrocytoma. However, they are rare diseases of low prevalence.
The interest in the cisplatin/irinotecan combination in brain tumours motivated a previous pilot study at our hospital, with encouraging results. This experience, together with the need for new strategies for high-risk pediatric gliomas has motivated the conduct of this study.
Read the detailed description
Tumours of the brain and of the central nervous system (CNS) are the most common solid tumours in children. Amongst these, gliomas are the most frequent, although this term covers different histological subtypes, the most frequent being astrocytoma. However, they are rare diseases of low prevalence.
The mortality rate of pediatric CNS cancer has not decreased in the same proportion as other tumours in children. High grade gliomas have a unfavorable prognosis with few therapeutic options. The objective response rate (ORR) of these tumours to chemotherapy ranges from 11% to 27%, in the best of cases. Relapsed high-grade gliomas and intrinsic brain stem tumours have a uniformly fatal outcome despite all the treatments tested. The treatment of adults with de novo glioblastoma after surgical resection is local radiotherapy concomitant to temozolomide. This approach in children is still under clinical assessment. In the case of low-grade astrocytomas, the indication for adjuvant therapy is limited to patients with unresectable tumours that also cause a neurological lesion. Although they are slow growing tumours, they can cause severe morbidity and are life-threatening. Radiotherapy has known side effects on the nervous system in children. Chemotherapy is used to delay or avoid radiotherapy in these patients.
Most of the radiological studies that evaluate treatment response of gliomas focus on measuring the area of the lesion. However, nowadays new imaging strategies and functional tests such as PET can be applied. The uptake of the 11C methionine tracer in tumour tissue is more selective than that of glucose and provides good delineation for the evaluation of these tumours.
There are few studies on the molecular and genetic characteristics of gliomas in children. In adults, it has been reported that microsatellite instability is a predictive factor of the tumour response to irinotecan, because the defect in the DNA repair proteins results in a greater sensitivity to the drug. Furthermore, in adults, 30-40% of the high grade astrocytomas show MGMT promotor methylation and as a consequence the methylated tumours are more sensitive to the effect of alkylating drugs. Due to the lack of pediatric studies on MGMT promoter methylation and on microsatellites the question as to whether their determination has the same importance as in high grade glioma in adults cannot be answered.
Irinotecan is a prodrug of the camptothecin family. Phase I and Phase II clinical trials using irinotecan in pediatric patients with different neoplasias demonstrate that irinotecan is well tolerated. The weekly administration of irinotecan and cisplatin in Phase I trials showed that treatment is well tolerated and the dose reached was 65 mg/m2 of irinotecan weekly together with cisplatin 30 mg/m2 weekly.
The interest in the cisplatin/irinotecan combination in brain tumours motivated a previous pilot study at our hospital, with encouraging results. This experience, together with the need for new strategies for high-risk pediatric gliomas has motivated the conduct of this study.
The impact of this study, if treatment proves to be effective, will be highly significant, given the poor response of gliomas to the adjuvant treatment used so far. Pediatric gliomas are of low incidence and may be considered as "orphan" diseases, and therefore as low priority as regards funding. However, because of their unfavorable prognosis these diseases have high clinical and social repercussions, especially high grade gliomas and high risk low grade gliomas, with less mortality but a high incidence of sequelae.
Other information relevant to the study
Phase II, single arm, open label trial, conducted at one institution, on the combination of two marketed drugs (irinotecan and cisplatin) in a new therapeutic indication.
Patients will receive weekly a 30 mg/m2 dose of cisplatin and a 65 mg/m2 dose of irinotecan (one cycle), up to a total of 16 cycles.
After 8 treatment cycles, Cohort 1 (recently diagnosed high-grade glioma) and Cohort 3 (intrinsic brain stem tumour) patients will be evaluated for treatment response and if there is disease progression they will be withdrawn from the trial and will receive conventional treatment with radiotherapy together with temozolomide (Stupp 2005). Patients with disease progression at any time during the trial will also be withdrawn. Patients who respond will continue until completing the 16 cycles of irinotecan and cisplatin at the end of which they will continue with conventional therapy. Cohort 2 (recurrent high-grade glioma) and Cohort 4 (high risk low-grade glioma) patients will also be evaluated after 8 cycles and if there is disease progression they will be withdrawn from the trial, if not they will complete the full 16 cycles.
- Conditions
- Pediatric High Risk Gliomas
- Being tested
- Combination of two marketed drugs (irinotecan and cisplatin)
- Keywords
- Pediatric, Pediatrics, Gliomas, Glioma, Brain tumor, Brain cancer, Cisplatin, Cisplatino, Irinotecan, Brain stem tumor, Brainstem gliomas, Intrinsic brain stem tumor, PAEDIATRIC HIGH GRADE GLIOMA, Childhood brain stem glioma
- Medical subject headings
- Glioma, Brain Neoplasms, Brain Stem Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination of two marketed drugs (irinotecan and cisplatin)Drug
Also called Irinotecan Hospira (20mg/ml), Cisplating Ferrer Farma(10mg or 50mg presentations)
Irinotecan and Cisplatin will be administered weekly ambulatory, intravenous (iv), until to reach a total of 16 cycles. Cisplatin is administered first and then Irinotecan. Cisplatin 30 mg/m2/d (iv) in one hour,followed by Irinotecan 65 mg/m2/d iv in one hour. There is a one-week rest period every 4 cycles. The total treatment length including 16 cycles + rest weeks is 19 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Irinotecan plus Cisplatin combination | Experimental | This is a open-label study with only one treatment experimental arm. The patients will be treated, in a weekly basis, with 30 mg/m2 of cisplatino plus 65 mg/m2 of irinotecán (one cycle), until a total of 16 cycles. Receives: Drug: Combination of two marketed drugs (irinotecan and cisplatin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of this study is to determine the safety and objective response rate (ORR).
The primary objective is to determine the safety and objective response rate (ORR), defined according to the criteria given in the CPMP/EWP/205/95/Rev.3/Corr.2, of irinotecan + cisplatin in pediatric patients with gliomas, through clinical signs and MR. The primary variable is the ORR.
Measured: Clinical signs, AEs, SAEs, ARs, SARs, Imaging and Audiometry changes: from baseline to FUP month 12.
Secondary outcomes (5)
Duration of the response.
The secondary variable has the aim to assess the duration of response by measuring the time to progression (TP), the time to treatment failure (TF) and overall survival (OS).
Measured: Clinical signs: baseline and every week (w1to21)+FUP month 3,6,9,12. Imaging (RM Baseline+w10&20+FUP month 3,6,9,12/PET: Baseline+w20).
Safety of the combined Irinotecan+Cisplatin therapy
The secondary variable aims to assess the safety of combined Irinotecan+Cisplatin therapy in study population (children and teens. Treatment safety will be assessed according to the Common Terminology Criteria for Adverse Events v3.0, (CTCAE).
Measured: Clinical signs, AEs, SAEs, ARs, SARs: baseline and every week (w1to21)+FUP month 3,6,9,12.Blood (hemo/chem):baseline&every week (w 1 to 21, except w10). Audiometry: baseline+w20+m6+m12.
Possible associations of gene MGMT promoter and microsatellites instability with reference to response to study treatment
The secondary variable aims to search if there could be any possible association between silent MGMT and the inestability of microsatellites with refernce to the response reached with the combined Irinotecan plus Cisplatin therapy in paediatrics glioma.
Measured: Clinical signs: baseline and every week (w1to21)+FUP month 3,6,9,12. Imaging (RM Baseline+w10&20+FUP month 3,6,9,12/PET: Baseline+w20). Genomic study: baseline (week-14 to-9)
To assess the applicability and efficacy of volumetric measurements as a treatment tumor-response indicator.
The aim of this secondary outcome measure is to assess the applicability and efficacy of the volumetric study measurement during the radiology assessment with reference to the tumour response to the study treatment.
Measured: Clinical signs: baseline (day-14to-9) and every week (w1to21)+FUP month 3,6,9,12. Imaging (RM Baseline day-14to -9 +w10&20+FUP month 3,6,9,12.
To assess the applicability and efficacy of metabolic study by PET-methionine
The aim of this secondary outcome measure is to assess the applicability and efficacy of the metabolic study by PET-methionine
Measured: Clinical signs: baseline (day-14to-9) and every week (w1to21)+FUP month 3,6,9,12. PET: Baseline day-14to -9 + w20).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2012 (estimated)
- Study startNov 2009
- Primary completionJun 2014
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Pediatric High Risk GliomasStudies 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
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Sant Joan de Deu
- Sponsor type
- University, hospital or other
- Collaborators
- Fundació Sant Joan de Déu, Spanish National Health System
- Responsible party
- Sponsor
- Investigators
- OFELIA CRUZ, MD, PhD, Principal investigator, HOSPITAL DE SANT JOAN DE DÈU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01574092
- Sponsor's protocol ID
- HSJD-GLIOMAS-IC
- Status last verified
- Aug 2015
- First submitted
- 29 Mar 2012
- Last updated
- 24 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Alonso M, Hamelin R, Kim M, Porwancher K, Sung T, Parhar P, Miller DC, Newcomb EW. Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors. Cancer Res. 2001 Mar 1;61(5):2124-8.
PubMed 11280776Blaney S, Berg SL, Pratt C, Weitman S, Sullivan J, Luchtman-Jones L, Bernstein M. A phase I study of irinotecan in pediatric patients: a pediatric oncology group study. Clin Cancer Res. 2001 Jan;7(1):32-7.
PubMed 11205914Bomgaars L, Berg SL, Blaney SM. The development of camptothecin analogs in childhood cancers. Oncologist. 2001;6(6):506-16. doi: 10.1634/theoncologist.6-6-506.
PubMed 11743213Bomgaars L, Kerr J, Berg S, Kuttesch J, Klenke R, Blaney SM. A phase I study of irinotecan administered on a weekly schedule in pediatric patients. Pediatr Blood Cancer. 2006 Jan;46(1):50-5. doi: 10.1002/pbc.20355.
PubMed 15768380Bomgaars LR, Bernstein M, Krailo M, Kadota R, Das S, Chen Z, Adamson PC, Blaney SM. Phase II trial of irinotecan in children with refractory solid tumors: a Children's Oncology Group Study. J Clin Oncol. 2007 Oct 10;25(29):4622-7. doi: 10.1200/JCO.2007.11.6103.
PubMed 17925558Bouffet E, Mottolese C, Jouvet A, Philip I, Frappaz D, Carrie C, Brunat-Mentigny M. Etoposide and thiotepa followed by ABMT (autologous bone marrow transplantation) in children and young adults with high-grade gliomas. Eur J Cancer. 1997 Jan;33(1):91-5. doi: 10.1016/s0959-8049(96)00369-3.
PubMed 9071906Brat DJ, Shehata BM, Castellano-Sanchez AA, Hawkins C, Yost RB, Greco C, Mazewski C, Janss A, Ohgaki H, Perry A. Congenital glioblastoma: a clinicopathologic and genetic analysis. Brain Pathol. 2007 Jul;17(3):276-81. doi: 10.1111/j.1750-3639.2007.00071.x. Epub 2007 Apr 23.
PubMed 17465990Broniscer A, Chintagumpala M, Fouladi M, Krasin MJ, Kocak M, Bowers DC, Iacono LC, Merchant TE, Stewart CF, Houghton PJ, Kun LE, Ledet D, Gajjar A. Temozolomide after radiotherapy for newly diagnosed high-grade glioma and unfavorable low-grade glioma in children. J Neurooncol. 2006 Feb;76(3):313-9. doi: 10.1007/s11060-005-7409-5.
PubMed 16200343Coggins CA, Elion GB, Houghton PJ, Hare CB, Keir S, Colvin OM, Bigner DD, Friedman HS. Enhancement of irinotecan (CPT-11) activity against central nervous system tumor xenografts by alkylating agents. Cancer Chemother Pharmacol. 1998;41(6):485-90. doi: 10.1007/s002800050771.
PubMed 9554593Cosetti M, Wexler LH, Calleja E, Trippett T, LaQuaglia M, Huvos AG, Gerald W, Healey JH, Meyers PA, Gorlick R. Irinotecan for pediatric solid tumors: the Memorial Sloan-Kettering experience. J Pediatr Hematol Oncol. 2002 Feb;24(2):101-5. doi: 10.1097/00043426-200202000-00009.
PubMed 11990694Crews KR, Stewart CF, Jones-Wallace D, Thompson SJ, Houghton PJ, Heideman RL, Fouladi M, Bowers DC, Chintagumpala MM, Gajjar A. Altered irinotecan pharmacokinetics in pediatric high-grade glioma patients receiving enzyme-inducing anticonvulsant therapy. Clin Cancer Res. 2002 Jul;8(7):2202-9.
PubMed 12114421Donson AM, Addo-Yobo SO, Handler MH, Gore L, Foreman NK. MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma. Pediatr Blood Cancer. 2007 Apr;48(4):403-7. doi: 10.1002/pbc.20803.
PubMed 16609952Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000 Nov 9;343(19):1350-4. doi: 10.1056/NEJM200011093431901.
PubMed 11070098Fallik D, Borrini F, Boige V, Viguier J, Jacob S, Miquel C, Sabourin JC, Ducreux M, Praz F. Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res. 2003 Sep 15;63(18):5738-44.
PubMed 14522894Finlay JL, Geyer JR, Turski PA, Yates AJ, Boyett JM, Allen JC, Packer RJ. Pre-irradiation chemotherapy in children with high-grade astrocytoma: tumor response to two cycles of the '8-drugs-in-1-day' regimen. A Childrens Cancer Group study, CCG-945. J Neurooncol. 1994;21(3):255-65. doi: 10.1007/BF01063775.
PubMed 7699420
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II, Single Arm, Open Label Clinical Trial With Irinotecan in Combination With Cisplatin in Pediatric Patients With Unfavorable Prognosis Gliomas
- ClinicalTrials.gov ID
- NCT01574092
- Acronym / sponsor ID
- HSJD-GLIOMAS-IC
- Conditions
- Pediatric High Risk Gliomas
- Keywords
- Pediatric, Pediatrics, Gliomas, Glioma, Brain tumor, Brain cancer, Cisplatin, Cisplatino
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Hospital Sant Joan de DeuUniversity, hospital or other
- Collaborators
- Fundació Sant Joan de Déu, Spanish National Health System
- Study start
- Nov 2009
- Primary completion
- Jun 2014 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 10 Apr 2012 (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.
Tumours of the brain and of the central nervous system (CNS) are the most common solid tumours in children. Amongst these, gliomas are the most frequent, although this term covers different histological subtypes, the most frequent being astrocytoma. However, they are rare diseases of low prevalence.
The interest in the cisplatin/irinotecan combination in brain tumours motivated a previous pilot study at our hospital, with encouraging results. This experience, together with the need for new strategies for high-risk pediatric gliomas has motivated the conduct of this study.
Detailed description
Tumours of the brain and of the central nervous system (CNS) are the most common solid tumours in children. Amongst these, gliomas are the most frequent, although this term covers different histological subtypes, the most frequent being astrocytoma. However, they are rare diseases of low prevalence.
The mortality rate of pediatric CNS cancer has not decreased in the same proportion as other tumours in children. High grade gliomas have a unfavorable prognosis with few therapeutic options. The objective response rate (ORR) of these tumours to chemotherapy ranges from 11% to 27%, in the best of cases. Relapsed high-grade gliomas and intrinsic brain stem tumours have a uniformly fatal outcome despite all the treatments tested. The treatment of adults with de novo glioblastoma after surgical resection is local radiotherapy concomitant to temozolomide. This approach in children is still under clinical assessment. In the case of low-grade astrocytomas, the indication for adjuvant therapy is limited to patients with unresectable tumours that also cause a neurological lesion. Although they are slow growing tumours, they can cause severe morbidity and are life-threatening. Radiotherapy has known side effects on the nervous system in children. Chemotherapy is used to delay or avoid radiotherapy in these patients.
Most of the radiological studies that evaluate treatment response of gliomas focus on measuring the area of the lesion. However, nowadays new imaging strategies and functional tests such as PET can be applied. The uptake of the 11C methionine tracer in tumour tissue is more selective than that of glucose and provides good delineation for the evaluation of these tumours.
There are few studies on the molecular and genetic characteristics of gliomas in children. In adults, it has been reported that microsatellite instability is a predictive factor of the tumour response to irinotecan, because the defect in the DNA repair proteins results in a greater sensitivity to the drug. Furthermore, in adults, 30-40% of the high grade astrocytomas show MGMT promotor methylation and as a consequence the methylated tumours are more sensitive to the effect of alkylating drugs. Due to the lack of pediatric studies on MGMT promoter methylation and on microsatellites the question as to whether their determination has the same importance as in high grade glioma in adults cannot be answered.
Irinotecan is a prodrug of the camptothecin family. Phase I and Phase II clinical trials using irinotecan in pediatric patients with different neoplasias demonstrate that irinotecan is well tolerated. The weekly administration of irinotecan and cisplatin in Phase I trials showed that treatment is well tolerated and the dose reached was 65 mg/m2 of irinotecan weekly together with cisplatin 30 mg/m2 weekly.
The interest in the cisplatin/irinotecan combination in brain tumours motivated a previous pilot study at our hospital, with encouraging results. This experience, together with the need for new strategies for high-risk pediatric gliomas has motivated the conduct of this study.
The impact of this study, if treatment proves to be effective, will be highly significant, given the poor response of gliomas to the adjuvant treatment used so far. Pediatric gliomas are of low incidence and may be considered as "orphan" diseases, and therefore as low priority as regards funding. However, because of their unfavorable prognosis these diseases have high clinical and social repercussions, especially high grade gliomas and high risk low grade gliomas, with less mortality but a high incidence of sequelae.
Other information relevant to the study
Phase II, single arm, open label trial, conducted at one institution, on the combination of two marketed drugs (irinotecan and cisplatin) in a new therapeutic indication.
Patients will receive weekly a 30 mg/m2 dose of cisplatin and a 65 mg/m2 dose of irinotecan (one cycle), up to a total of 16 cycles.
After 8 treatment cycles, Cohort 1 (recently diagnosed high-grade glioma) and Cohort 3 (intrinsic brain stem tumour) patients will be evaluated for treatment response and if there is disease progression they will be withdrawn from the trial and will receive conventional treatment with radiotherapy together with temozolomide (Stupp 2005). Patients with disease progression at any time during the trial will also be withdrawn. Patients who respond will continue until completing the 16 cycles of irinotecan and cisplatin at the end of which they will continue with conventional therapy. Cohort 2 (recurrent high-grade glioma) and Cohort 4 (high risk low-grade glioma) patients will also be evaluated after 8 cycles and if there is disease progression they will be withdrawn from the trial, if not they will complete the full 16 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Irinotecan plus Cisplatin combination | Experimental | Drug: Combination of two marketed drugs (irinotecan and cisplatin)This is a open-label study with only one treatment experimental arm. The patients will be treated, in a weekly basis, with 30 mg/m2 of cisplatino plus 65 mg/m2 of irinotecán (one cycle), until a total of 16 cycles. |
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Histological confirmation of neoplasia, except for intrinsic brain stem tumour and optic pathway glioma in one patient with neurofibromatosis type 1 (NF1).
- Pertaining to one of the diagnostic groups: Cohort 1: Recently diagnosed high grade glioma. Cohort 2: Recurrent high grade glioma. Cohort 3: Intrinsic brain stem tumour. Cohort 4: High risk low grade glioma.
- Measurable primary or metastatic tumours with at least one 10 mm diameter lesion in two MR dimensions.
- Absence of prior treatment with cisplatin or irinotecan.
- Aged between 6 months to 18 years.
Key exclusion criteria (5 listed)
- Concurrent administration of any other anti-cancer treatment.
- Pre-existing, non-controlled diarrhoea
- Pregnancy or lactation
- Treatment in another clinical trial.
- Serious concomitant disease that could compromise the completion of the trial. -
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 |
|---|---|---|
| Combination of two marketed drugs (irinotecan and cisplatin)Also: Irinotecan Hospira (20mg/ml), Cisplating Ferrer Farma(10mg or 50mg presentations)Irinotecan and Cisplatin will be administered weekly ambulatory, intravenous (iv), until to reach a total of 16 cycles. Cisplatin is administered first and then Irinotecan. Cisplatin 30 mg/m2/d (iv) in one hour,followed by Irinotecan 65 mg/m2/d iv in one hour. There is a one-week rest period every 4 cycles. The total treatment length including 16 cycles + rest weeks is 19 weeks. | Drug | Irinotecan plus Cisplatin combination |
Primary outcome
The primary objective of this study is to determine the safety and objective response rate (ORR).
Time frame: Clinical signs, AEs, SAEs, ARs, SARs, Imaging and Audiometry changes: from baseline to FUP month 12.
The primary objective is to determine the safety and objective response rate (ORR), defined according to the criteria given in the CPMP/EWP/205/95/Rev.3/Corr.2, of irinotecan + cisplatin in pediatric patients with gliomas, through clinical signs and MR. The primary variable is the ORR.
5 secondary outcomes
Duration of the response.
Time frame: Clinical signs: baseline and every week (w1to21)+FUP month 3,6,9,12. Imaging (RM Baseline+w10&20+FUP month 3,6,9,12/PET: Baseline+w20).
Safety of the combined Irinotecan+Cisplatin therapy
Time frame: Clinical signs, AEs, SAEs, ARs, SARs: baseline and every week (w1to21)+FUP month 3,6,9,12.Blood (hemo/chem):baseline&every week (w 1 to 21, except w10). Audiometry: baseline+w20+m6+m12.
Possible associations of gene MGMT promoter and microsatellites instability with reference to response to study treatment
Time frame: Clinical signs: baseline and every week (w1to21)+FUP month 3,6,9,12. Imaging (RM Baseline+w10&20+FUP month 3,6,9,12/PET: Baseline+w20). Genomic study: baseline (week-14 to-9)
To assess the applicability and efficacy of volumetric measurements as a treatment tumor-response indicator.
Time frame: Clinical signs: baseline (day-14to-9) and every week (w1to21)+FUP month 3,6,9,12. Imaging (RM Baseline day-14to -9 +w10&20+FUP month 3,6,9,12.
To assess the applicability and efficacy of metabolic study by PET-methionine
Time frame: Clinical signs: baseline (day-14to-9) and every week (w1to21)+FUP month 3,6,9,12. PET: Baseline day-14to -9 + w20).
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 24 Aug 2015.
- Background: PubMed 11280776Alonso M, Hamelin R, Kim M, Porwancher K, Sung T, Parhar P, Miller DC, Newcomb EW. Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors. Cancer Res. 2001 Mar 1;61(5):2124-8.
- Background: PubMed 11205914Blaney S, Berg SL, Pratt C, Weitman S, Sullivan J, Luchtman-Jones L, Bernstein M. A phase I study of irinotecan in pediatric patients: a pediatric oncology group study. Clin Cancer Res. 2001 Jan;7(1):32-7.
- Background: PubMed 11743213Bomgaars L, Berg SL, Blaney SM. The development of camptothecin analogs in childhood cancers. Oncologist. 2001;6(6):506-16. doi: 10.1634/theoncologist.6-6-506.
- Background: PubMed 15768380Bomgaars L, Kerr J, Berg S, Kuttesch J, Klenke R, Blaney SM. A phase I study of irinotecan administered on a weekly schedule in pediatric patients. Pediatr Blood Cancer. 2006 Jan;46(1):50-5. doi: 10.1002/pbc.20355.
- Background: PubMed 17925558Bomgaars LR, Bernstein M, Krailo M, Kadota R, Das S, Chen Z, Adamson PC, Blaney SM. Phase II trial of irinotecan in children with refractory solid tumors: a Children's Oncology Group Study. J Clin Oncol. 2007 Oct 10;25(29):4622-7. doi: 10.1200/JCO.2007.11.6103.
- Background: PubMed 9071906Bouffet E, Mottolese C, Jouvet A, Philip I, Frappaz D, Carrie C, Brunat-Mentigny M. Etoposide and thiotepa followed by ABMT (autologous bone marrow transplantation) in children and young adults with high-grade gliomas. Eur J Cancer. 1997 Jan;33(1):91-5. doi: 10.1016/s0959-8049(96)00369-3.
- Background: PubMed 17465990Brat DJ, Shehata BM, Castellano-Sanchez AA, Hawkins C, Yost RB, Greco C, Mazewski C, Janss A, Ohgaki H, Perry A. Congenital glioblastoma: a clinicopathologic and genetic analysis. Brain Pathol. 2007 Jul;17(3):276-81. doi: 10.1111/j.1750-3639.2007.00071.x. Epub 2007 Apr 23.
- Background: PubMed 16200343Broniscer A, Chintagumpala M, Fouladi M, Krasin MJ, Kocak M, Bowers DC, Iacono LC, Merchant TE, Stewart CF, Houghton PJ, Kun LE, Ledet D, Gajjar A. Temozolomide after radiotherapy for newly diagnosed high-grade glioma and unfavorable low-grade glioma in children. J Neurooncol. 2006 Feb;76(3):313-9. doi: 10.1007/s11060-005-7409-5.
- Background: PubMed 9554593Coggins CA, Elion GB, Houghton PJ, Hare CB, Keir S, Colvin OM, Bigner DD, Friedman HS. Enhancement of irinotecan (CPT-11) activity against central nervous system tumor xenografts by alkylating agents. Cancer Chemother Pharmacol. 1998;41(6):485-90. doi: 10.1007/s002800050771.
- Background: PubMed 11990694Cosetti M, Wexler LH, Calleja E, Trippett T, LaQuaglia M, Huvos AG, Gerald W, Healey JH, Meyers PA, Gorlick R. Irinotecan for pediatric solid tumors: the Memorial Sloan-Kettering experience. J Pediatr Hematol Oncol. 2002 Feb;24(2):101-5. doi: 10.1097/00043426-200202000-00009.
- Background: PubMed 12114421Crews KR, Stewart CF, Jones-Wallace D, Thompson SJ, Houghton PJ, Heideman RL, Fouladi M, Bowers DC, Chintagumpala MM, Gajjar A. Altered irinotecan pharmacokinetics in pediatric high-grade glioma patients receiving enzyme-inducing anticonvulsant therapy. Clin Cancer Res. 2002 Jul;8(7):2202-9.
- Background: PubMed 16609952Donson AM, Addo-Yobo SO, Handler MH, Gore L, Foreman NK. MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma. Pediatr Blood Cancer. 2007 Apr;48(4):403-7. doi: 10.1002/pbc.20803.
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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.
OFELIA CRUZ, MD, PhD principal investigator
HOSPITAL DE SANT JOAN DE DÈU
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Combination of two marketed drugs (irinotecan and cisplatin) in people with Pediatric High Risk Gliomas, run by Hospital Sant Joan de Deu at 1 site in Spain.
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 12 inclusion and 5 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 24 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. 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?
The primary objective of this study is to determine the safety and objective response rate (ORR). (time frame: Clinical signs, AEs, SAEs, ARs, SARs, Imaging and Audiometry changes: from baseline to FUP month 12.). 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 NCT01574092, which also lists 23 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 24 Aug 2015.