Clinical trial NCT01735747: Temozolomide, Nedaplatin, Vincristine, and Radiotherapy as First-line Treatment in Newly Diagnosed Primary CNS Lymphoma
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Central Nervous System Tumors
Keywords: Lymphoma
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
First posted: 2012-11-28
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of complete radiologic response (CR)
timeFrame: 3 years
Secondary outcomes:
measure: Failure-free survival
timeFrame: 3 years
measure: Toxicity
timeFrame: 3 years
measure: Overall response rate
timeFrame: 3 years
Other outcomes:
Locations:
city: Jinan
country: China
facility: Neurosurgery, Shandong Cancer Hospital and Institute
state: Shandong
Study officials:
affiliation: Shandong Cancer Hospital and Institute
name: Yu-fang Zhu, M.D.
role: STUDY_DIRECTOR
affiliation: Shandong Cancer Hospital and Institute
name: Yong Wang, M.M.
role: STUDY_DIRECTOR
References:
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. doi: 10.1038/sj.bjc.6603660. Epub 2007 Feb 27.
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.
citation: 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. doi: 10.1200/JCO.2002.11.013.