Clinical trial NCT02803151: A Clinical Trial of Stereotactic Ablative Radiotherapy for Metastatic Lymphadenopathy
Official title: A Prospective Phase II Clinical Trial of Stereotactic Ablative Radiotherapy for Metastatic Lymphadenopathy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Metastasis of Malignant Neoplasm to Lymph Node
Keywords: Stereotactic ablative radiotherapy
Lymph node metastasis
T cell immunity
cell-free DNA
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2016-06-16
Enrollment: 59
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Lymph node metastasis is one of the most common sites to develop disease recurrence or progression after initial local treatment for primary solid malignancies or systemic treatment for advanced metastases. No specific treatment modality has been established as the standard therapy. Systemic therapy is usually considered since lymphadenopathy is considered as a sign of disease dissemination though aggressive local treatment, including surgical lymphoadenectomy or radical radiotherapy might result in long-term survival in selected patients. The concept of stereotactic ablative radiotherapy (SABR), a high dose of radiation targeted to a pathological entity and delivered in a few fractions, has proven so successful at treating both benign and malignant lesions that it changed the paradigm for radiation therapy. The radiobiology of SABR has been shown to be very favorable for tumor control. Clinical experiences suggested that SABR might offer excellent in-field tumor control with low toxicity profile in selected patients, although the majority of reports are retrospective and include small patients series with heterogeneous tumor sites and dose-fractionation schedules.

At present, there is lack of validated prognostic factors to identify the patients who might benefit most from ablative local therapy for metastatic lymph node(s). The mechanism of effect of SABR on the cancer lesions is not yet clear. Apart from its direct effect on clonogenic cancer cells, an immune-mediated process was also hypothesized. Therefore, the present study is aimed to provide a better understanding about utilization of SABR for metastatic lymph node(s). The associated translational researches will also advance our knowledge in the immune system reactions to SABR.

Detailed description: This is a single institutional, single-arm, phase II trial to assess the local control rate of oligo-metastatic or oligo-progressive lymph node treated by stereotactic ablative radiotherapy at 1 year.

Patients with pathologically proven non-hematopoietic malignancy patients with radiographic evidence of evaluable regional recurrent, oligo-metastatic or oligo-progressive lymph nodes are eligible for enrolment.

Stereotactic Ablative Radiotherapy:

The lymph node planning target volume (PTV) will receive the prescribed dose according to the assigned treatment group. The dose is prescribed such as 90-95% of PTV is covered by the prescription dose. If the critical structures exceed the defined dose limitation, a dose reduction method is applied as protocol defined. Dose inhomogeneity can exist within the clinical target volume (CTV).

Treatment will be delivered in six fractions to the target volume and given once per day, 2-3 fractions per week with no more than 2 daily consecutive fractions, over 2 to 2.5 weeks.

Target Radiation Dose: SABR with 45 Gy in six fractions to the defined target volume with met organ-at-risk constraint criteria using intensity modulated radiotherapy or volumetric modulated arc therapy (VMAT or RapidArc).

Radiation Dose Reduction:

Reduced Dose 10%: SABR with 40.05 Gy in six fractions to the defined target volume with met organ-at-risk constraint criteria

Reduced Dose 20%: SABR with 36 Gy in six fractions to the defined target volume with met organ-at-risk constraint criteria

Eligibility criteria: Inclusion criteria

1. Patients with a histologic diagnosis of non-hematopoietic malignancy
2. Radiographic evidence of measurable enlarged metastatic lymph node(s) with short-axis ≥ 1 cm
3. Patients do not have prior radiotherapy to the index node(s)
4. Age ≥ 20 years
5. Karnofsky performance status (KPS) ≥ 60%.
6. Life expectancy of ≥ 4 month
7. Patients must have adequate renal function with serum creatinine ≤ 2.0 mg/dL measured within 90 days prior to registration
8. Women of childbearing potential and male participants must practice adequate contraception
9. Patients must be able to comply with the study protocol and follow-up schedules and provide study-specific informed consent

Exclusion criteria

1. Prior radiotherapy to the index metastatic lymph node(s)
2. Sum of the greatest dimensions of index lymph note(s) exceed 6 cm
3. Inability to achieve the minimal required radiation dose (36Gy)
4. Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:

   1. Uncontrolled active infection requiring intravenous antibiotics at the time of registration
   2. Transmural myocardial infarction ≤ 6 months prior to registration
   3. Unstable angina or congestive heart failure requiring hospitalization ≤ 6 months prior to registration
   4. Life-threatening uncontrolled clinically significant cardiac arrhythmias
   5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
   6. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
   7. Uncontrolled psychiatric disorder
5. Will receive any other investigational agent or chemotherapy and/or target therapies during treatment
6. Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic

Primary outcomes:
measure: Local control (Response Evaluation Criteria In Solid Tumors version 1.1)
timeFrame: 12 months
Secondary outcomes:
measure: Patient reported outcome (Quality of Life questionnaire)
timeFrame: at 1, 3 months after radiotherapy, and every 3 month thereafter until unequivocal progression, hospice care, or death, assessed up to 12 months
measure: Acute toxicity (Common Toxicity Criteria for Adverse Events version 4)
timeFrame: From date of radiotherapy until 90 days after radiotherapy starts
measure: Late toxicity (Common Toxicity Criteria for Adverse Events version 4)
timeFrame: From 90 days after radiotherapy starts until the date of death from any cause, up to 60 months
measure: Metastatic nodal progression
timeFrame: From date of enrolment until the date of first documented metastatic nodal progression or date of death from any cause, whichever came first, assessed up to 60 months
measure: Overall survival
timeFrame: From date of enrollment until the date of death from any cause, assessed up to 60 months
Other outcomes:
measure: Changes of peripheral blood lymphocyte subpopulations
timeFrame: at baseline, 2 weeks, 1, 2, 3, 6, and 12 months after radiotherapy
Locations:
city: Tapei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Feng-Ming Hsu, MD
role: PRINCIPAL_INVESTIGATOR
References: