Procarbazine and Lomustine in Recurrent Glioblastoma

Study Overview
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Brief Summary
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The combination therapy of temozolomide and radiation has been established as the standard therapy for the initial treatment of glioblastoma. However, the prognosis for patients with recurrent/ refractory glioblastoma is dismal, with a median survival of 3 6 months. There is no efficient and standard care at the time of recurrence or progression following temozolomide administration. Recently, many clinicians have reassessed the efficacy of second-line chemotherapeutic agents such as nitrosoureas for the treatment of recurrent/refractory glioblastoma. It is very important that the effect of the agent is sustained and the adverse effect is reduced to preserve the quality of life in recurrent settings. We have realized that the clinical features of Korean patients are very different from those of foreign patients. Therefore, it is mandatory to develop the new strategy for the treatment of Korean patients. We modify the PCV chemotherapy in the dose and administration schedule of CCNU and procarbazine to reduce the side effect, especially hematologic problems. The dose of CCNU is reduced to 75mg/m2 and the interval between CCNU and procarbazine is increased. Moreover, vincristine is excluded because BBB permeability of vincristine is very poor and the risk of neurotoxicity is high. We introduce the modified PC chemotherapy regimen for the treatment of recurrent/refractory glioblastoma, which is the first multicenter trial for glioblastoma patients in Korea.

Official Title
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Phase 2 Clinical Trial of PC(Procarbazine-CCNU) Chemotherapy in Patients With Recurrent or Resistant Glioblastoma With Methylated MGMT

Conditions
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Recurrent Glioblastoma Multiforme

Intervention / Treatment
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* Drug: lomustine and procarbazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or radiologically confirmed progressive or recurrent glioblastoma with methylated MGMT promoter Within 6 months after or during Stupp regimen (TMZ-RT CCRT + adjuvant TMZ), or After re-treatment of cyclic TMZ, 6 months later after Stupp regimen KPS ≥ 60% Age ≥ 20 years At least two weeks apart from prior surgery and prior chemotherapy Adequate hematologic, liver, and renal functions Unstained slides for central pathology review Signed informed consent Exclusion Criteria: Prior malignancy within 5 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and carcinoma in situ of the cervix maternity or breastfeeding Evidence of active infection within 2 weeks prior to study Previous treatment with procarbazine and/or CCNU Evidence of leptomeningeal metastasis Unable to comply with the study protocol

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lomustine and procarbazine<br>1 cycle (4 weeks) includes CCNU 75mg/m2 (D1) and procarbazine 60mg/m2 (D11-D24)by mouth for up to 6 cycles | Drug: lomustine and procarbazine<br>* 1 cycle (4 weeks) includes CCNU 75mg/m2 (D1) and procarbazine 60mg/m2 (D11-D24)by mouth for up to 6 cycles<br>* Other names: Matulan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month progression free survival |  | March 31, 2014 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glioblastoma, recurrent, refractory, CCNU, procarbazine