PineoblastomaPhase 2NCT02596828
Prospective Pilot Trial to Assess a Multimodal Molecular Targeted Therapy in Children, Adolescent and Young Adults With Relapsed or Refractory High-grade Pineoblastoma
A Phase 2 study testing Temozolomide, Irinotecan and Dasatinib in people with Pineoblastoma, run by University of Regensburg at 1 site in Germany.
Trial summary
Children, adolescents and young adults with relapsed or treatment refractory pineoblastoma (rPB) represent a group of patients with dismal prognosis for whom a recommended standard salvage therapy is currently not available. Read more about this study
- Who is it for?
- Ages 0 to 25 years
- Conditions the study is for
- Pineoblastoma
- What is being tested?
- Temozolomide, Irinotecan and Dasatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2016to Apr 2021
- 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 0 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with relapsed and refractory high-grade pineoblastome (=rPB) and all of the following criteria will be considered for admission to the clinical trial:
- Children, adolescents and young adults 0 months to 25 years
- Signed written informed consent (patient or his/her parents/legal guardian)
- Females of childbearing age must have a negative urine pregnancy test prior to starting the study drug. The first pregnancy test must be performed within 10-14 days prior to the start of the study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug. The subject may not receive the study drug until the investigator has verified that the results of these pregnancy tests are negative.
- Females of childbearing age must comply with the institutional standards of birth control with a pearl index <1%. Contraception must be started at least four weeks before the start of the investigational therapy.
- Females of childbearing age must be willing to abstain from breastfeeding for the duration of the clinical trial and for at least 30 days after discontinuation of the clinical trial.
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- Males must agree not to father a child and must use latex condom during any sexual contact with women of childbearing age during and for 6 months after therapy ends or is stopped, even if they have undergone successful vasectomy.
- Willing and able to complete the clinical trial procedures, as described in the protocol
- Non-smoker for at least the previous 3 months. Smoking is not allowed during the entire study period
- Abstain from alcohol within the last 24 hours before screening and before admission to the clinical trial center as well as during the entire clinical trial. The regular daily ethanol intake has to be less than 20g/day for at least the previous three months.
- Patients are required to have an absolute neutrophil count (ANC) ≥500/µL, hemoglobin ≥8g/dL (transfusion permitted), and an unsupported platelet count ≥30,000/µL unless:
- patient is refractory or relapsed early after primary therapy
Who cannot join
- Patients presenting with any of the following criteria will not be included in this clinical trial:
- Pregnancy, nursing
- Patients who suffered from a thrombotic event and need anticoagulation (i.e. coumadine derivatives or low molecular weight heparin derivatives, LMWH)
- Patients with cardiac arrhythmias especially prolonged QT
- Patients with chronic inflammatory bowel diseases and/or bowel obstruction
- Patients with bilirubin serum levels 1,5 fold above the upper normal limit
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- Vaccination with a live virus vaccine during the clinical trial
- Impaired liver function and/or impaired renal function (hepatic and renal index parameter two times above normal range; see below)
- Potentially unreliable subjects, probably non compliant subjects and those judged by the investigator to be unsuitable for the study
- Doubts about the patient's cooperation
- Any contraindications or known hypersensitivity to the IMPs or to any of the other components: (see SPC "Fachinformation")
- Known allergic reactions to the treatment medication
- Patients who were treated with radiation and/or chemotherapy for any other oncological condition
- Participation in any other interventional phase I to III trial
- Sexually active patients who refuse to use contraception according to the institutional requirements
- Patients with extremely poor general condition (Karnofsky or Lansky score <50%)
- Neutrophil count (ANC) <500/µL, hemoglobin <8g/dL (transfusion permitted), and an unsupported platelet count <30 000/µL
- 12-lead ECG with QTc>500 msec / QTc>60 msec baseline
- Patients with hepatitis B reactivation
Trial locations and contacts
1 site in 1 country.
About this study
Children, adolescents and young adults with relapsed or treatment refractory pineoblastoma (rPB) represent a group of patients with dismal prognosis for whom a recommended standard salvage therapy is currently not available.
Read the detailed description
The multimodal metronomic approach combining molecular targeted drugs (rapamycin and dasatinib) with conventional chemotherapy (irinotecan and temozolomide) will be investigated in a randomized fashion as new treatment strategy for patients with rPB. The intention is to assess the therapeutic benefit of molecular targeted drugs for the treatment of rPB.
The combination of irinotecan and temozolomide showed activity in the treatment of several solid organ tumors, brain tumors and neuroblastoma. In one study relapsed neuroblastoma (rNB) patients received a median of 5 courses of 5 days irinotecan and temozolomide every 3 to 4 weeks with a cumulative dose of 35% lower than in the RIST design. 33% had disease regression with 8% CR or PR. A phase II study in rNB also using irinotecan and temozolomide with a substantially lower intensity showed a response rate of 15%.
The combination of a mTOR inhibitor with a multi-kinase inhibitor demonstrated in preclinical studies a synergistic effect on cell cycle arrest, apoptosis and sensitization for radio- and chemotherapy. It is assumed that this combination of molecular targeted drugs with a tolerable conventional chemotherapy consisting of irinotecan and temozolomide can substantially improve the outcome of this patient population. A group of 20 rNB patients treated with the RIST therapy approach in a compassionate use setting showed an overall survival of 55% at a median of 80 weeks with a tolerable adverse event profile.
- Conditions
- Pineoblastoma
- Being tested
- Temozolomide, Irinotecan, Dasatinib, Rapamycin
- Keywords
- molecular targeted therapy, protein kinase inhibitor, mTOR Inhibitor, cytostatic topoisomerase-I-inhibitor, temozolomide, irinotecan, dasatinib, rapamycin
- Medical subject headings
- Pinealoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called Temomedac
Pharmacotherapeutic Group: Antineoplastic agents - Other alkylating agents, ATC-Code: L01A X03 Excipients: Capsule content: Anhydrous lactose, Sodium starch glycolate Type A, Colloida anhydrous silica, Tartaric acid, Stearic acid. Capsule shell: Gelatine, Titanium dioxide (E171).
Printing ink: Shellac Propylene glycol, Titanium dioxide (E171), Sunset yellow FCF Aluminium Lake (E110) Formulation: capsule, hard Route of Administration: orally; Temomedac hard capsules should be administered in the fasting state. The capsules must be swallowed whole with a glass of water and must not be opened or chewed
IrinotecanDrug
Also called Irinomedac
Pharmacotherapeutic Group: cytostatic topoisomerase-I-inhibitor ATC-Code: L01XX19 Excipients: Sorbitol (E420), lactic acid, sodium hydroxid (to adjust the pH to 3.5), water for injection Formulation: concentrate for solution for infusion Route of Administration: intravenously
DasatinibDrug
Also called Sprycel
Pharmacotherapeutic Group: protein kinase inhibitor ATC-Code: L01XE06 Excipients: Tablet core: Lactose monohydrate, Cellulose, microcrystalline, Croscarmellose sodium, Hydroxypropyl cellulose, Magnesium stearate. Film-coating: Hypromellose, Titanium dioxide, Macrogol 400 Formulation: film coated tablet Route of Administration: orally. Patients should be instructed to swallow the tablets as a whole and not to split, chew, or crush them.
RapamycinDrug
Also called Rapamune
Pharmacotherapeutic Group: Immunosuppressive agents - mTOR Inhibitors ATC-Code: L04A A10 Excipients: Polysorbat 80, Phosal 50 PG ((3-sn-Phosphatidyl)cholin from Soy beans, Propylenglycol, lipid acid mono- and -diglyzeride from Soy oil, Ethanol (1,5% bis 2,5%), Soy liid acid and Palmitoyl ascorbic acid) Formulation: Oral solution Route of Administration:orally
| Study group | Role | What they receive |
|---|---|---|
| RIST | Experimental | Not described Receives: Drug: Temozolomide; Drug: Irinotecan; Drug: Dasatinib; Drug: Rapamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is progression-free survival (PFS)
According to:
- Imaging criteria to
- MRI, CT or
- CSF evaluations or
- date of death of any cause
Measured: Time interval from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks
Secondary outcomes (6)
Overall survival (OS)
According to: questionnaire
Measured: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
Response to the investigational treatment after 4 and 8 courses of I/T and 1-year-follow-up in the RIST treatment arm
According to:
- Imaging criteria to
- MRI, CT or
- CSF evaluations
Measured: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
Duration until adequate response to this treatment regimen
According to:
- Imaging criteria to
- MRI, CT or
- CSF evaluations
Measured: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
Assessment of quality of life (Lansky and Karnofsky Scores)
According to:
Lansky and Karnofsky Scores
Measured: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
Toxicity of this combination of drugs in children, adolescents and young adults with rNB - Assessment according to the latest version of the CTC criteria
Assessment according to the latest version of the CTC criteria. In particular due to the expected AE Profile:
Myelosuppressive measures (RBC, PLT units) Infectious complications Gastrointestinal problems
Measured: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
Safety and tolerability of the investigational treatment - Assessment according to the latest version of the CTC criteria
Assessment according to the latest version of the CTC criteria. In particular due to the expected AE Profile:
Myelosuppressive measures (RBC, PLT units) Infectious complications Gastrointestinal problems
Measured: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2015 (estimated)
- Study startApr 2016
- Primary completionApr 2021
- Study completionApr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PineoblastomaStudies 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
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Regensburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Dr. med. Selim Corbacioglu, University of Regensburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02596828
- Sponsor's protocol ID
- RIST-rPB-2015-P
- Status last verified
- Jul 2021
- First submitted
- 28 Oct 2015
- Last updated
- 5 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Pilot Trial to Assess a Multimodal Molecular Targeted Therapy in Children, Adolescent and Young Adults With Relapsed or Refractory High-grade Pineoblastoma
- ClinicalTrials.gov ID
- NCT02596828
- Acronym / sponsor ID
- RIST-rPB-2015-P
- Conditions
- Pineoblastoma
- Keywords
- molecular targeted therapy, protein kinase inhibitor, mTOR Inhibitor, cytostatic topoisomerase-I-inhibitor, temozolomide, irinotecan, dasatinib, rapamycin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of RegensburgUniversity, hospital or other
- Study start
- Apr 2016
- Primary completion
- Apr 2021 (actual)
- Study completion
- Apr 2021 (actual)
- First posted
- 4 Nov 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.
Children, adolescents and young adults with relapsed or treatment refractory pineoblastoma (rPB) represent a group of patients with dismal prognosis for whom a recommended standard salvage therapy is currently not available.
Detailed description
The multimodal metronomic approach combining molecular targeted drugs (rapamycin and dasatinib) with conventional chemotherapy (irinotecan and temozolomide) will be investigated in a randomized fashion as new treatment strategy for patients with rPB. The intention is to assess the therapeutic benefit of molecular targeted drugs for the treatment of rPB.
The combination of irinotecan and temozolomide showed activity in the treatment of several solid organ tumors, brain tumors and neuroblastoma. In one study relapsed neuroblastoma (rNB) patients received a median of 5 courses of 5 days irinotecan and temozolomide every 3 to 4 weeks with a cumulative dose of 35% lower than in the RIST design. 33% had disease regression with 8% CR or PR. A phase II study in rNB also using irinotecan and temozolomide with a substantially lower intensity showed a response rate of 15%.
The combination of a mTOR inhibitor with a multi-kinase inhibitor demonstrated in preclinical studies a synergistic effect on cell cycle arrest, apoptosis and sensitization for radio- and chemotherapy. It is assumed that this combination of molecular targeted drugs with a tolerable conventional chemotherapy consisting of irinotecan and temozolomide can substantially improve the outcome of this patient population. A group of 20 rNB patients treated with the RIST therapy approach in a compassionate use setting showed an overall survival of 55% at a median of 80 weeks with a tolerable adverse event profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RIST | Experimental | Drug: Temozolomide, Drug: Irinotecan, Drug: Dasatinib, Drug: Rapamycin |
Who may qualify
- Ages
- 0 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Patients with relapsed and refractory high-grade pineoblastome (=rPB) and all of the following criteria will be considered for admission to the clinical trial:
- Children, adolescents and young adults 0 months to 25 years
- Signed written informed consent (patient or his/her parents/legal guardian)
- Females of childbearing age must have a negative urine pregnancy test prior to starting the study drug. The first pregnancy test must be performed within 10-14 days prior to the start of the study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug. The subject may not receive the study drug until the investigator has verified that the results of these pregnancy tests are negative.
- Females of childbearing age must comply with the institutional standards of birth control with a pearl index <1%. Contraception must be started at least four weeks before the start of the investigational therapy.
Key exclusion criteria (19 listed)
- Patients presenting with any of the following criteria will not be included in this clinical trial:
- Pregnancy, nursing
- Patients who suffered from a thrombotic event and need anticoagulation (i.e. coumadine derivatives or low molecular weight heparin derivatives, LMWH)
- Patients with cardiac arrhythmias especially prolonged QT
- Patients with chronic inflammatory bowel diseases and/or bowel obstruction
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 |
|---|---|---|
| TemozolomideAlso: TemomedacPharmacotherapeutic Group: Antineoplastic agents - Other alkylating agents, ATC-Code: L01A X03 Excipients: Capsule content: Anhydrous lactose, Sodium starch glycolate Type A, Colloida anhydrous silica, Tartaric acid, Stearic acid. Capsule shell: Gelatine, Titanium dioxide (E171). Printing ink: Shellac Propylene glycol, Titanium dioxide (E171), Sunset yellow FCF Aluminium Lake (E110) Formulation: capsule, hard Route of Administration: orally; Temomedac hard capsules should be administered in the fasting state. The capsules must be swallowed whole with a glass of water and must not be opened or chewed | Drug | RIST |
| IrinotecanAlso: IrinomedacPharmacotherapeutic Group: cytostatic topoisomerase-I-inhibitor ATC-Code: L01XX19 Excipients: Sorbitol (E420), lactic acid, sodium hydroxid (to adjust the pH to 3.5), water for injection Formulation: concentrate for solution for infusion Route of Administration: intravenously | Drug | RIST |
| DasatinibAlso: SprycelPharmacotherapeutic Group: protein kinase inhibitor ATC-Code: L01XE06 Excipients: Tablet core: Lactose monohydrate, Cellulose, microcrystalline, Croscarmellose sodium, Hydroxypropyl cellulose, Magnesium stearate. Film-coating: Hypromellose, Titanium dioxide, Macrogol 400 Formulation: film coated tablet Route of Administration: orally. Patients should be instructed to swallow the tablets as a whole and not to split, chew, or crush them. | Drug | RIST |
| RapamycinAlso: RapamunePharmacotherapeutic Group: Immunosuppressive agents - mTOR Inhibitors ATC-Code: L04A A10 Excipients: Polysorbat 80, Phosal 50 PG ((3-sn-Phosphatidyl)cholin from Soy beans, Propylenglycol, lipid acid mono- and -diglyzeride from Soy oil, Ethanol (1,5% bis 2,5%), Soy liid acid and Palmitoyl ascorbic acid) Formulation: Oral solution Route of Administration:orally | Drug | RIST |
Primary outcome
The primary endpoint is progression-free survival (PFS)
Time frame: Time interval from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks
According to: * Imaging criteria to * MRI, CT or * CSF evaluations or * date of death of any cause
6 secondary outcomes
Overall survival (OS)
Time frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
Response to the investigational treatment after 4 and 8 courses of I/T and 1-year-follow-up in the RIST treatment arm
Time frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
Duration until adequate response to this treatment regimen
Time frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
Assessment of quality of life (Lansky and Karnofsky Scores)
Time frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
Toxicity of this combination of drugs in children, adolescents and young adults with rNB - Assessment according to the latest version of the CTC criteria
Time frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
Safety and tolerability of the investigational treatment - Assessment according to the latest version of the CTC criteria
Time frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks
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 5 Aug 2021.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Temozolomide, Irinotecan and Dasatinib in people with Pineoblastoma, run by University of Regensburg at 1 site 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 12 inclusion and 19 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 5 Aug 2021. 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 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?
The primary endpoint is progression-free survival (PFS) (time frame: Time interval from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks). 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 5 Aug 2021.