Metronomic Temozolamide in Patients With Recurrent Glioblastoma

• Status: Unknown status
• Trial end date: 2012-06-01
• Target enrollment: 0
• Participant gender: All

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 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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Grupo Español de Investigación en Neurooncología
• Treatments: Camptothecin; Irinotecan

Criteria

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.