Clinical trial · Interventional

Metronomic Temozolamide in Patients With Recurrent Glioblastoma

PHASE I-II TRIAL OF METRONOMIC TEMOZOLAMIDE WITH INTERMITTENT INTENSIFICATION AND IRINOTECAN IN PATIENTS WITH RECURRENT GLIOBLASTOMA

NCT01308632CI-TRIAL-00004509unknownPhase 2 / Phase 3ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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 28-day cycles. 2. 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.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Glioblastoma	Glioblastoma	CURATED_BROADER	0.80

Interventions

Interventions (1)

Intervention	Type	Mapped drug	Match
Temozolamide, irinotecan	Drug	—	UNRESOLVED

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Temozolamide, irinotecan
description
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 .
interventionNames
1. Drug: Temozolamide, irinotecan

Primary outcomes (2)

measure
Efficacy of the treatment (Phase I)
timeFrame
every patient should receive at least one cycle ( 28 days)
description
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
measure

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

Inclusion Criteria:

1. Patients \> 18 years old
2. 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.
3. Karnofsky performance status ≥ 70.
4. 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.
5. Stable or descending corticosteroid dose ≥ 72 hours before baseline MRI and study treatment.
6. Life expectancy greater than 3 months
7. Written informed consent.

Exclusion Criteria:

1. Pregnancy or breastfeeding.
2. Neurological impairment that precludes comprehension or treatment administration
3. Vomiting or other condition that interfere with oral administration of TMZ
4. Previous or concurrent malignancy, excluding basal cell carcinomas or in situ cervical cancer.
5. Concurrent disease that could interfere with treatment
6. 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.

References

Publications (0)

Data not yet available

No reference posted for this study.