GlioblastomaPhase 2/3NCT01308632
Metronomic Temozolamide in Patients With Recurrent Glioblastoma
A Phase 2/3 study testing Temozolamide, irinotecan in people with Glioblastoma, run by Grupo Español de Investigación en Neurooncología.
Trial summary
Indication: Subjects with glioblastoma at first relapse after surgery, radiotherapy and first-line temozolomide (TMZ). Objectives: 1. Phase I endpoint: To determine the maximum tolerated dose (MTD) of CPT-11 administered on days 8 and 22 in combination with a fixed, continuous, and metronomic regimen of TMZ, given in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Temozolamide, irinotecan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Nov 2007to Jun 2012
- Phase
- Phase 2/3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients > 18 years old
- Histological confirmed GB at first relapse, assessed by MRI scan, after surgical resection or biopsy, radiotherapy, and first-line chemotherapy with TMZ. A TMZ treatment duration of at least 3 months is required. Previous chemotherapy with CPT-11 is not allowed.
- Karnofsky performance status ≥ 70.
- ANC ≥ 1500/ μl, platelet count ≥ 100000/ μl, haemoglobin > 10 g/dl, serum creatinine and total bilirubin < 1.5 times the upper limit of laboratory normal, transaminases < 3.0 times the upper limit of laboratory normal.
- Stable or descending corticosteroid dose ≥ 72 hours before baseline MRI and study treatment.
- Life expectancy greater than 3 months
- Written informed consent.
Who cannot join
- Pregnancy or breastfeeding.
- Neurological impairment that precludes comprehension or treatment administration
- Vomiting or other condition that interfere with oral administration of TMZ
- Previous or concurrent malignancy, excluding basal cell carcinomas or in situ cervical cancer.
- Concurrent disease that could interfere with treatment
- Concurrent treatment with enzyme-inducing drugs. Patients under enzyme-inducing anticonvulsants should discontinue treatment at least one week before study treatment and begin a new anti-epileptic treatment with non enzyme-inducing drugs if indicated.
About this study
Official title: PHASE I-II TRIAL OF METRONOMIC TEMOZOLAMIDE WITH INTERMITTENT INTENSIFICATION AND IRINOTECAN IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Indication:
Subjects with glioblastoma at first relapse after surgery, radiotherapy and first-line temozolomide (TMZ).
Read more
Objectives:
- Phase I endpoint:
- To determine the maximum tolerated dose (MTD) of CPT-11 administered on days 8 and 22 in combination with a fixed, continuous, and metronomic regimen of TMZ, given in 28-day cycles.
- Phase II endpoints:
Primary endpoint: Progression-free survival at 6 months. Secondary endpoints: Response rate, toxicity profile, overall survival.
Complementary studies:
To assess the effect of treatment on plasma concentration of thrombospondin-1 (TSP1), soluble VEGF receptor 1 (sVEGF-1) and VEGF-A, and their correlation with clinical outcome.
- To assess the correlation between immunohistochemical expression of PTEN and MGMT proteins, and clinical outcomes.
Read the detailed description
Study Design: Open label, phase I - II trial. Phase I trial: TMZ will be administered in a fixed schedule as follows:
TMZ
- 50 mg/m2/day divided in three daily doses (approx. 17 mg/m2/8 hours) on days 1-7, 9-21, and 23-28.
- 100 mg/m2 in a morning single dose on days 8 and 22
CPT-11 starting dose:
.100 mg/m2 on days 8 and 22, administered 3 to 6 hours after TMZ.(Level 1).One cycle = 28 days. CPT-11 will be escalated in successive cohorts of 3 patients as follows: 115, 130, 145, 160 mg/m2 .
Three patients will be treated at dose level 1. If there is no DLT, 3 new patients will be treated at dose level 2, and so on. If 1 or 2 of the 3 patients initially recruited at each treatment level experience DLT, 3 additional patients will be included at the same level. If DLT is registered in less than 3 of the 6 patients treated at this level, 3 new patients will be included in the next dose level. If 3 or more of the 6 patients experience DLT, the phase I trial will be closed and the previous treatment level will be chosen for the phase II trial. If all 3 initial patients at one level experience DLT, the previous dose level will be used in the phase II trial.
If DLT is found at dose level 1, phase I trial will be re-started at level -2 (70 mg/m2 ) and -1 (85 mg/m2).
Definition of DLT:
- Absolute neutrophil count (ANC) < 500/ μl > 7 days
- Platelet count < 25000/ μl
- A delay in starting a new cycle by > 7 days to allow recovery from toxicity (ANC ≥ 1500/ μl and platelet count ≥ 100000/ μl
- Febrile Neutropenia
- Non-haematological toxicity grade 3-4, except alopecia and nausea/vomiting or diarrhea without adequate prophylaxis or treatment.
Phase II trial: Patients will receive the treatment schedule at the dose level stated in the phase I study. Treatment will be maintained until progression or excessive toxicity.
Patient evaluation: A physical examination, blood count, and basic biochemistry assessment will be performed within 3 weeks before treatment and at each study visit. Tumor recurrence or progression has to be demonstrated by MRI scan performed within 3 weeks before the first treatment course and after every second course of chemotherapy. The assessment of tumor response will be based on criteria defined by Macdonald et al. Study visits will be performed on days 1, 8, 15 and 22 of first and second treatment course, and on days 8 and 22 thereafter, if no significant toxicity has been observed.
Complementary studies: The immunohistochemical expression of PTEN and MGMT will be assessed in paraffin sections of tumor tissue of all patients.
Blood samples for enzyme immunoassay of TSP1, sVEGFR-1 and VEGF-A will be collected within 3 weeks before treatment, after course 1 and every 3 treatment courses thereafter.
- Conditions
- Glioblastoma
- Being tested
- Temozolamide, irinotecan
- Keywords
- glioblastoma, temozolamide, radiotherapy, TMZ, irinotecan
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temozolamide, irinotecanDrug
Also called CPT-11, Campto, Irinotecan, Temozolamide
Phase I trial:
TMZ will be administered in a fixed schedule as follows:
TMZ 50 mg/m2/day divided in three daily doses (approx. 17 mg/m2/8 hours) on days 1-7, 9-21, and 23-28.
100 mg/m2 in a morning single dose on days 8 and 22
CPT-11 starting dose:
100 mg/m2 on days 8 and 22, administered 3 to 6 hours after TMZ. (Level 1)
One cycle = 28 days
CPT-11 will be escalated in successive cohorts of 3 patients as follows: 115, 130, 145, 160 mg/m2 .
| Study group | Role | What they receive |
|---|---|---|
| Temozolamide, irinotecan | Experimental | Phase I trial:
TMZ will be administered in a fixed schedule as follows:
TMZ 50 mg/m2/day divided in three daily doses (approx. 17 mg/m2/8 hours) on days 1-7, 9-21, and 23-28.
100 mg/m2 in a morning single dose on days 8 and 22
CPT-11 starting dose:
100 mg/m2 on days 8 and 22, administered 3 to 6 hours after TMZ. (Level 1)
One cycle = 28 days
CPT-11 will be escalated in successive cohorts of 3 patients as follows: 115, 130, 145, 160 mg/m2 . Receives: Drug: Temozolamide, irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of the treatment (Phase I)
To determine the maximum tolerated dose (MTD) of CPT-11 administered on days 8 and 22 in combination with a fixed, continuous and metronomic regimen of TMZ, given in 28-days cycles to use the Recommended Dose in phase II
Measured: every patient should receive at least one cycle ( 28 days)
Progression-free survival (Phase II)
The time the patient is not in progression, since the beginning of the treatment
Measured: Since the initial of the treatment until the patient progression
Secondary outcomes (3)
Assess the toxicity of the treatment
Toxicity Profile (in phase II)
Measured: the patients will be followed until disease progression
Progression-free survival at 6 months
Progression-free survival at 6 months (Phase I)
Measured: 6 months since the pacient is included in the trial
overall survival
Measured: the patients will be followed until death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2011 (estimated)
- Study startNov 2007
- Primary completionJun 2012 (estimated)
- Study completionJun 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Español de Investigación en Neurooncología
- Sponsor type
- University, hospital or other
- Investigators
- Reynés Gaspar, Dr, Principal investigator, Hospital Universitario La Fe de Valencia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01308632
- Sponsor's protocol ID
- GENOM-007
- Status last verified
- Mar 2011
- First submitted
- 24 Jan 2011
- Last updated
- 4 Mar 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PHASE I-II TRIAL OF METRONOMIC TEMOZOLAMIDE WITH INTERMITTENT INTENSIFICATION AND IRINOTECAN IN PATIENTS WITH RECURRENT GLIOBLASTOMA
- ClinicalTrials.gov ID
- NCT01308632
- Acronym / sponsor ID
- GENOM-007
- Conditions
- Glioblastoma
- Keywords
- glioblastoma, temozolamide, radiotherapy, TMZ, irinotecan
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Grupo Español de Investigación en NeurooncologíaUniversity, hospital or other
- Study start
- Nov 2007
- Primary completion
- Jun 2012 (estimated)
- Study completion
- Jun 2012 (estimated)
- First posted
- 4 Mar 2011 (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.
Indication:
Subjects with glioblastoma at first relapse after surgery, radiotherapy and first-line temozolomide (TMZ).
Objectives:
- Phase I endpoint:
- To determine the maximum tolerated dose (MTD) of CPT-11 administered on days 8 and 22 in combination with a fixed, continuous, and metronomic regimen of TMZ, given in 28-day cycles.
- Phase II endpoints:
Primary endpoint: Progression-free survival at 6 months. Secondary endpoints: Response rate, toxicity profile, overall survival.
Complementary studies:
To assess the effect of treatment on plasma concentration of thrombospondin-1 (TSP1), soluble VEGF receptor 1 (sVEGF-1) and VEGF-A, and their correlation with clinical outcome.
- To assess the correlation between immunohistochemical expression of PTEN and MGMT proteins, and clinical outcomes.
Detailed description
Study Design: Open label, phase I - II trial. Phase I trial: TMZ will be administered in a fixed schedule as follows:
TMZ
- 50 mg/m2/day divided in three daily doses (approx. 17 mg/m2/8 hours) on days 1-7, 9-21, and 23-28.
- 100 mg/m2 in a morning single dose on days 8 and 22
CPT-11 starting dose:
.100 mg/m2 on days 8 and 22, administered 3 to 6 hours after TMZ.(Level 1).One cycle = 28 days. CPT-11 will be escalated in successive cohorts of 3 patients as follows: 115, 130, 145, 160 mg/m2 .
Three patients will be treated at dose level 1. If there is no DLT, 3 new patients will be treated at dose level 2, and so on. If 1 or 2 of the 3 patients initially recruited at each treatment level experience DLT, 3 additional patients will be included at the same level. If DLT is registered in less than 3 of the 6 patients treated at this level, 3 new patients will be included in the next dose level. If 3 or more of the 6 patients experience DLT, the phase I trial will be closed and the previous treatment level will be chosen for the phase II trial. If all 3 initial patients at one level experience DLT, the previous dose level will be used in the phase II trial.
If DLT is found at dose level 1, phase I trial will be re-started at level -2 (70 mg/m2 ) and -1 (85 mg/m2).
Definition of DLT:
- Absolute neutrophil count (ANC) < 500/ μl > 7 days
- Platelet count < 25000/ μl
- A delay in starting a new cycle by > 7 days to allow recovery from toxicity (ANC ≥ 1500/ μl and platelet count ≥ 100000/ μl
- Febrile Neutropenia
- Non-haematological toxicity grade 3-4, except alopecia and nausea/vomiting or diarrhea without adequate prophylaxis or treatment.
Phase II trial: Patients will receive the treatment schedule at the dose level stated in the phase I study. Treatment will be maintained until progression or excessive toxicity.
Patient evaluation: A physical examination, blood count, and basic biochemistry assessment will be performed within 3 weeks before treatment and at each study visit. Tumor recurrence or progression has to be demonstrated by MRI scan performed within 3 weeks before the first treatment course and after every second course of chemotherapy. The assessment of tumor response will be based on criteria defined by Macdonald et al. Study visits will be performed on days 1, 8, 15 and 22 of first and second treatment course, and on days 8 and 22 thereafter, if no significant toxicity has been observed.
Complementary studies: The immunohistochemical expression of PTEN and MGMT will be assessed in paraffin sections of tumor tissue of all patients.
Blood samples for enzyme immunoassay of TSP1, sVEGFR-1 and VEGF-A will be collected within 3 weeks before treatment, after course 1 and every 3 treatment courses thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Temozolamide, irinotecan | Experimental | Drug: Temozolamide, irinotecanPhase I trial: TMZ will be administered in a fixed schedule as follows: TMZ 50 mg/m2/day divided in three daily doses (approx. 17 mg/m2/8 hours) on days 1-7, 9-21, and 23-28. 100 mg/m2 in a morning single dose on days 8 and 22 CPT-11 starting dose: 100 mg/m2 on days 8 and 22, administered 3 to 6 hours after TMZ. (Level 1) One cycle = 28 days CPT-11 will be escalated in successive cohorts of 3 patients as follows: 115, 130, 145, 160 mg/m2 . |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients > 18 years old
- Histological confirmed GB at first relapse, assessed by MRI scan, after surgical resection or biopsy, radiotherapy, and first-line chemotherapy with TMZ. A TMZ treatment duration of at least 3 months is required. Previous chemotherapy with CPT-11 is not allowed.
- Karnofsky performance status ≥ 70.
- ANC ≥ 1500/ μl, platelet count ≥ 100000/ μl, haemoglobin > 10 g/dl, serum creatinine and total bilirubin < 1.5 times the upper limit of laboratory normal, transaminases < 3.0 times the upper limit of laboratory normal.
- Stable or descending corticosteroid dose ≥ 72 hours before baseline MRI and study treatment.
Key exclusion criteria (6 listed)
- Pregnancy or breastfeeding.
- Neurological impairment that precludes comprehension or treatment administration
- Vomiting or other condition that interfere with oral administration of TMZ
- Previous or concurrent malignancy, excluding basal cell carcinomas or in situ cervical cancer.
- Concurrent disease that could interfere with treatment
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 |
|---|---|---|
| Temozolamide, irinotecanAlso: CPT-11, Campto, Irinotecan, TemozolamidePhase I trial: TMZ will be administered in a fixed schedule as follows: TMZ 50 mg/m2/day divided in three daily doses (approx. 17 mg/m2/8 hours) on days 1-7, 9-21, and 23-28. 100 mg/m2 in a morning single dose on days 8 and 22 CPT-11 starting dose: 100 mg/m2 on days 8 and 22, administered 3 to 6 hours after TMZ. (Level 1) One cycle = 28 days CPT-11 will be escalated in successive cohorts of 3 patients as follows: 115, 130, 145, 160 mg/m2 . | Drug | Temozolamide, irinotecan |
Primary outcome
Efficacy of the treatment (Phase I)
Time frame: every patient should receive at least one cycle ( 28 days)
To determine the maximum tolerated dose (MTD) of CPT-11 administered on days 8 and 22 in combination with a fixed, continuous and metronomic regimen of TMZ, given in 28-days cycles to use the Recommended Dose in phase II
Progression-free survival (Phase II)
Time frame: Since the initial of the treatment until the patient progression
The time the patient is not in progression, since the beginning of the treatment
3 secondary outcomes
Assess the toxicity of the treatment
Time frame: the patients will be followed until disease progression
Progression-free survival at 6 months
Time frame: 6 months since the pacient is included in the trial
overall survival
Time frame: the patients will be followed until death
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2011.
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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.
Reynés Gaspar, Dr principal investigator
Hospital Universitario La Fe de Valencia
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Temozolamide, irinotecan in people with Glioblastoma, run by Grupo Español de Investigación en Neurooncología.
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 7 inclusion and 6 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 4 Mar 2011. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
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?
Efficacy of the treatment (Phase I) (time frame: every patient should receive at least one cycle ( 28 days)). 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 4 Mar 2011.