Clinical trial NCT02229682: Mild-dose IMRT for Early-staged Extranodal Nasal-type NK/T-cell Lymphoma With CR Tumor After GELOX Chemotherapy
Official title: Mild-dose Intensity-modulated Radiation Treatment for Stage IE/IIE Extranodal Nasal-type NK/T-cell Lymphoma With Complete Remission Tumor After Combination of Gemcitabine, Oxaliplatin, and Asparaginase (GELOX) Chemotherapy:a Phase II Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lymphoma,
Non-Hodgkin Lymphoma,
Extranodal NK/T-cell Lymphoma,Nasal-type,
Keywords: extranodal NK/T-cell lymphoma,nasal-type,
radiotherapy,
intensity-modulated radiation treatment,
asparaginase-based chemotherapy,
loco-regional control,
survival
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2014-09-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is to make sure whether reduced-dose radiation treatment is sufficient to control the disease in patients with early-staged extranodal nasal-type NK/T-cell lymphoma, who have got complete remission tumor after chemotherapy in a new and more effective asparaginase-based GELOX regimen

Detailed description: Definitive radiotherapy(RT) is mainstay in combined-modality treatment for patients with early-staged extranodal nasal-type NK/T-cell lymphoma(ENKTL),it can be used upfront or after short courses of chemotherapy. The typical dose of RT is recommended as 50-56Gy in conventional fractionations with 3 dimensional conformal RT or intensity-modulated radiation treatment(IMRT). Asparaginase-based chemotherapy regimens are being investigated, and primary results showed superior to previous anthracycline-based (eg. CHOP) chemotherapy. GELOX is a new asparaginase-based chemotherapy regimen designed and published in our institute, and the rate of complete remission(CR) is well improved. We hypothesis the reduced-dose radiation treatment(IMRT in 46Gy) is sufficient to control the disease in patients with early-staged ENKTL, who have got CR after GELOX chemotherapy, and to validate in this phase II study.

1. Patients:

   * All patients should sign a written informed consent form before enrollment, and the study should be approved by the Sun Yat-sen University Cancer Center Ethics Board.
   * Baseline of patients: Computed tomography (CT) scans of the chest, abdomen, and pelvis, magnetic resonance imaging studies of the head and neck, and bilateral bone marrow aspiration or biopsy. Positron emission tomography-CT scans (optional). Epstein-Barr virus (EBV) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA).
   * Recheck before and after GELOX chemotherapy and IMRT: Epstein-Barr virus (EBV) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA), computed tomography (CT) scans of the chest, abdomen, and pelvis, magnetic resonance imaging studies of the head and neck, positron emission tomography-CT scans (optional).
2. Treatment Protocol:

   1. The GELOX regimen consist of the following drugs: gemcitabine：1250 mg/ m2 on days 1,iv drip; oxaliplatin：85 mg/m2 on day 1, iv drip; pegaspargase: 2500 IU/m 2 daily on day 1,intramuscular. The treatment cycle is repeated every 14 days.
   2. IMRT is delivered using 6-8MeV linear accelerator using extended involved-field intensity-modulated radiation treatment planning. The RT dose is 46.2 grays (Gy) in 22 fractions, and a simultaneous-boost method is used.

      * We assign gross tumor volume (GTV) to 46.2Gy/22F, which is delineated according to the initial gross tumor volume identified with imaging and physical examination, including the primary tumor and involved regional lymph nodes.
      * The high-risk clinical target volume (CTV1) is assigned to 41.8Gy/22F, which is delineated including the first batch of adjacent structures around GTV, and lymph node group apt for involvement according to clinical feature of individual tumors.
      * The low-risk clinical target volume (CTV2) is assigned to 36.3Gy/22F, which is delineated including the extrapolated structures outside of CTV1 sites, and LN groups adjacent to CTV1 LN groups.

Eligibility criteria: Inclusion Criteria:

* newly diagnosed ENKTL
* age:18-75years
* Ann Arbor stage IE,or stage IIE with cervical lymph node involvement
* at lease one measurable lesion
* received GELOX chemotherapy and got CR before radiotherapy
* Eastern CooperativeOncology Group performance status of 0 to 2
* Adequate hematologic function (eg, white blood cell ≥ 3×10e9/l,neutrophils count ≥1.5×10e9/L, and platelet count≥ 100×10e9/L),renal function (eg, serum creatinine≤1.5 mg/dL and creatinine clearance ≥50 mL minute), and hepatic function (e.g, total bilirubin≤ 2 times the upper limit of normal and aspartate and alanine transaminase levels ≤ 3 times the upper limit of normal)

Exclusion Criteria:

* mismatch the inclusion criteria,
* got non-CR after GELOX chemotherapy before IMRT,
* systematic central nervous system involvement, previous or concomitant malignancies and any coexisting medical problems that could cause poor compliance with the study protocol,
* primary lesion not from the upper aerodigestive tract

Primary outcomes:
measure: loco-regional tumor control
timeFrame: every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years.
Secondary outcomes:
measure: progression-free survival(PFS)
timeFrame: every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years
measure: overall survival(OS)
timeFrame: every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Dept. Radiation Oncology, Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Yujing Zhang, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang L, Wang ZH, Chen XQ, Li YJ, Wang KF, Xia YF, Xia ZJ. First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/T-cell lymphoma. Cancer. 2013 Jan 15;119(2):348-55. doi: 10.1002/cncr.27752. Epub 2012 Jul 18.
citation: Gregoire V, Ang K, Budach W, Grau C, Hamoir M, Langendijk JA, Lee A, Le QT, Maingon P, Nutting C, O'Sullivan B, Porceddu SV, Lengele B. Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines. Radiother Oncol. 2014 Jan;110(1):172-81. doi: 10.1016/j.radonc.2013.10.010. Epub 2013 Oct 31.