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

Central Nervous System Tumors Clinical Trial

Official title:

Phase Ⅱ Trial of Temozolomide Plus Concurrent Whole-Brain Radiation Followed by TNV Regimen as Adjuvant Therapy for Patients With Newly Diagnosed Primary Central Nervous System (CNS) Lymphoma (PCNSL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01735747
• Other study ID #: ShandongCHI 002
• Status: Active, not recruiting
• Phase: Phase 2
• First received: November 23, 2012
• Last updated: March 11, 2013
• Start date: June 2008
• Est. completion date: November 2013

Study information

• Verified date: March 2013
• Source: Shandong Cancer Hospital and Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 16
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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 ß-HCG) or lactating.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Central Nervous System Neoplasms
• Central Nervous System Tumors
• Nervous System Neoplasms

Intervention

Radiation:
• Radiotherapy
WBRT was given five times a week at 2 gray (Gy)/d until the whole brain radiotherapy dose reached 40 gray. The patients were given concurrent temozolomide (75mg/m2, orally) daily during radiotherapy until the end of radiotherapy.

Drug:
• nedaplatin
nedaplatin (80mg/m2 i.v., day 1), 28 day schedule, performed four weeks after radiotherapy.A maximum of six cycles were applied.
• vincristine
vincristine (1.4mg/m2 i.v., day 1)28 day schedule,performed four weeks after radiotherapy.A maximum of six cycles were applied.
• Temozolomide
Temozolomide (200mg/m2 orally, days 1-5, Each cycle was 4 weeks ), performed four weeks after radiotherapy. A maximum of six cycles were applied.

Locations

Country	Name	City	State
China	Neurosurgery, Shandong Cancer Hospital and Institute	Jinan	Shandong

Sponsors (2)

Lead Sponsor	Collaborator
Rongjie Tao	National Natural Science Foundation of China

Country where clinical trial is conducted

China, 

References & Publications (3)

DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol. 2002 Dec 15;20(24):4643-8. — View Citation

Kurzwelly D, Glas M, Roth P, Weimann E, Lohner H, Waha A, Schabet M, Reifenberger G, Weller M, Herrlinger U. Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status. J Neurooncol. 2010 May;97(3):389-92. doi: 10.1007/s11060-009-0032-0. Epub 2009 Oct 20. — View Citation

Reni M, Zaja F, Mason W, Perry J, Mazza E, Spina M, Bordonaro R, Ilariucci F, Faedi M, Corazzelli G, Manno P, Franceschi E, Pace A, Candela M, Abbadessa A, Stelitano C, Latte G, Ferreri AJ. Temozolomide as salvage treatment in primary brain lymphomas. Br J Cancer. 2007 Mar 26;96(6):864-7. Epub 2007 Feb 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of complete radiologic response (CR)	final data collection date for primary outcome measure	3 years	No
Secondary	Failure-free survival		3 years	No
Secondary	Toxicity		3 years	Yes
Secondary	Overall response rate		3 years	No