Temozolomide, Nedaplatin, Vincristine, and Radiotherapy as First-line Treatment in Newly Diagnosed Primary CNS Lymphoma

Phase 2

• Conditions: Central Nervous System Tumors
• Interventions: Radiation: Radiotherapy; Drug: nedaplatin; Drug: vincristine; Drug: Temozolomide

• Registration Number: NCT01735747
• Lead Sponsor: Rongjie Tao

Brief Summary

In this trial, we will treat newly diagnosed PCNSL with temozolomide, nedaplatin, vincristine (TNV) as the replacement of high-dose methotrexate to combine with concurrent chemoradiotherapy. Our objective was to assess our treatment strategies' availability based on response rates, progression-free survival (PFS), median PFS, and toxicity.

Detailed Description

The best reported outcomes of PCNSL treatment are high-dose methotrexate-based chemotherapy combined with whole-brain radiation therapy (WBRT). Despite aggressive therapy, however, nearly 50% of patients will relapse within 24 months of diagnosis. Furthermore, the application of high-dose methotrexate-based regimen is complex, needing be hydrated, alkalified and detoxified, and treatment-related toxicity mortality is severe\[3,4\]. In an attempt to improve upon these poor results and reduce treatment-related side effects, we will treat about 15-20 PCNSL patients with temozolomide concurrent chemoradiotherapy at the outset and then adjuvant chemotherapy for 6 cycles with temozolomide, nedaplatin, vincristine, as part of front-line therapy. Our objective is to assess our treatment strategies' availability based on response rates, progression-free survival (PFS), median PFS, and toxicity.

Study Timeline

• Study Start: 2008-06
• Study First Submitted: 2012-11-23
• Study First Submitted QC: 2012-11-27
• Study First Posted: 2012-11-28
• Status Verified: 2013-03
• Last Update Submitted: 2013-03-11
• Last Update Posted: 2013-03-12
• Primary Completion: 2013-11
• Study Completion: 2013-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Histologically confirmed primary CNS lymphoma.
• Newly diagnosed.
• ECOG (Eastern Cooperative Oncology Group) Performance status of 0-1.
• Relevant hospital examination including laboratory examination and physical examination (Chest X-ray, electrocardiogram, abdomen B ultrasonography, magnetic resonance imaging (MRI) of head and neck) must to be done, in order to exclude other system fatal diseases.
• Must have adequate organ function as defined by the protocol: Adequate renal function: serum creatinine ≤ 1.5 mg/dl and/or calculated creatinine clearance ≥ 60 ml/min; Adequate hepatic function: bilirubin level ≤ 1.5 x ULN, ASAT & ALST ≤ 1.5 x ULN.Adequate bone marrow reserves: neutrophil (ANC) count ≥ 1500 /mm^3, platelet count ≥ 100,000 /mm^3, hemoglobin ≥ 9 g/dl.
• Age >/= 18 and </= 75 years
• Signed written informed consent prior to study entry.

Exclusion Criteria

• Patients with human immunodeficiency virus seropositivity and systemic lymphoma manifestation.
• Serious uncontrolled concurrent illness.
• Previous brain radiotherapy, systemic chemotherapy.
• Concurrent chronic systemic immune therapy, targeted therapy not indicated in this study protocol.
• Any evidence of prior exposure to Hepatitis B virus.
• Unable to comprehend the study requirements or who are not likely to comply with the study parameters.
• Pregnant (confirmed by serum or urine β-HCG) or lactating.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Temozolomide, Nedaplatin, Vincristine, Radiotherapy	Radiotherapy	The newly diagnosed PCNSL patients will be given concurrent temozolomide (75mg/m2, orally) daily during WBRT. Then, the TNV regimen will be given after four weeks. TNV regimen consisted of temozolomide (200mg/m2 orally, days 1-5), nedaplatin (80mg/m2 i.v., day 1), vincristine (1.4mg/m2 i.v., day 1). Each cycle was 4 weeks and a maximum of six cycles were applied.
Temozolomide, Nedaplatin, Vincristine, Radiotherapy	Temozolomide	The newly diagnosed PCNSL patients will be given concurrent temozolomide (75mg/m2, orally) daily during WBRT. Then, the TNV regimen will be given after four weeks. TNV regimen consisted of temozolomide (200mg/m2 orally, days 1-5), nedaplatin (80mg/m2 i.v., day 1), vincristine (1.4mg/m2 i.v., day 1). Each cycle was 4 weeks and a maximum of six cycles were applied.
Temozolomide, Nedaplatin, Vincristine, Radiotherapy	nedaplatin	The newly diagnosed PCNSL patients will be given concurrent temozolomide (75mg/m2, orally) daily during WBRT. Then, the TNV regimen will be given after four weeks. TNV regimen consisted of temozolomide (200mg/m2 orally, days 1-5), nedaplatin (80mg/m2 i.v., day 1), vincristine (1.4mg/m2 i.v., day 1). Each cycle was 4 weeks and a maximum of six cycles were applied.
Temozolomide, Nedaplatin, Vincristine, Radiotherapy	vincristine	The newly diagnosed PCNSL patients will be given concurrent temozolomide (75mg/m2, orally) daily during WBRT. Then, the TNV regimen will be given after four weeks. TNV regimen consisted of temozolomide (200mg/m2 orally, days 1-5), nedaplatin (80mg/m2 i.v., day 1), vincristine (1.4mg/m2 i.v., day 1). Each cycle was 4 weeks and a maximum of six cycles were applied.

Primary Outcome Measures

Name	Time	Method
Rate of complete radiologic response (CR)	3 years	final data collection date for primary outcome measure

Secondary Outcome Measures

Name	Time	Method
Failure-free survival	3 years
Toxicity	3 years
Overall response rate	3 years

Trial Locations

Locations (1)

Neurosurgery, Shandong Cancer Hospital and Institute; 🇨🇳 Jinan, Shandong, China