Supplementation of L-arginine in Patients With Non-resectable Brain Metastases
- Conditions
- Unresectable Multiple Brain Metastases
- Interventions
- Dietary Supplement: L-arginine hydrochloride solutionOther: Placebo
- Registration Number
- NCT02844387
- Lead Sponsor
- Instituto de Oncología Ángel H. Roffo
- Brief Summary
This study evaluates the nutritional supplement arginine as supportive measure for patients with unresectable metastatic brain tumors that receive radiation therapy with palliative intent
- Detailed Description
Brain metastasis, the most common intracranial tumor, is associated with neurological disability and short survival time. For selected patients this outcome can be improved by achieving greater local control. Virtually all cancer patients with brain metastases receive radiotherapy; a majority as part of their primary treatment while others in connection with surgery or palliation. Agents that increase the sensitivity of cancer cells to radiation may improve the control of the disease. Previous data indicates that arginine supplementation can modify the metabolism of cancer and immune cells making tumors more susceptible to standard treatments liked radiation. In this phase 1/2 comparative study the investigators will investigate whether 10 mg of arginine oral supplementation (compared to placebo administration) administered twice a day prior to the radiation therapy can modify tumor metabolism, immune response and effect of radiation. The primary end-points are safety and toxicity of arginine, quality-of-life and clinical response. The secondary end-points are imaging response and neurological progression-free survival. Additional exploratory end-points include intensity of radiation administered, effects on tumor metabolism by magnetic resonance spectroscopy, immune response by cytokine pattern in serum, body composition and nutritional parameters , overall survival and progression free survival
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 70
- Unresectable criteria by neurosurgeon
- Recursive partitioning analysis (RPA) -Radiation Therapy Oncology Group (RTOG) class II (Karnofsky's performance score ≥ 70 and extracranial metastases and/or non-controlled primary tumor)
- Measurable brain lesion/s by contrast-enhanced CT or MRI
- Absolute granulocyte count more or equal than 2000/mm3
- Hemoglobin more or equal than 9 g/L (patients with lower levels were transfused before the randomization)
- Normal renal laboratory (serum creatinine <1.5 mg/dL and 24-h creatinine clearance >60 mL/min)
- Normal hepatic function (aspartate aminotransferase and alanine aminotransferase <2.5 times the upper limit of normal)
- Stable body weight and composition for at least one month prior enrollment
- Prior treatment for brain metastases and/or brain tumor.
- Primary brain tumor
- Hematologic malignancies
- Solid tumors of germinal origin
- Contraindication for external radiation therapy.
- Allergy to L-arginine.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arginine L-arginine hydrochloride solution In the Arginine arm patients will receive 10 mg of L-arginine hydrochloride solution oral supplementation (in 200 ml of flavoured drinking water solution) administered twice a day prior to the radiation therapy fraction Placebo Placebo In the Placebo arm patients will receive 200 ml of flavoured drinking water oral solution administered twice a day prior to the radiation therapy fraction
- Primary Outcome Measures
Name Time Method Change from baseline of the scoring form NCI CTCAE v3 for detecting and quantifying potential adverse events Baseline and thereafter every 7 days starting from day 1 of L-arginine or placebo administration and through study completion, an average of 1 year NCI CTCAE v3 form will be completed baseline and every 7 days starting from day 1 of L-arginine or placebo administration thereafter. This form will detect adverse events including clinical laboratory alterations associated with the administration of of L-arginine or placebo including those that may exacerbate the adverse events expected from the radiation therapy
Change from baseline in signs and symptoms of neurological disease Baseline and at 4 weeks counted from the last day of treatment Signs and symptoms of neurological disease will be evaluated by caregiver and investigator according to response criteria evaluation guidelines. Clinical response will be considered as the changes in signs and symptoms that occur between baseline state and 30 days counted from the last day of treatment
Change from baseline of quality of life questionnaire Baseline and thereafter every 7 days starting from day 1 of L-arginine or placebo administration and through study completion, an average of 1 year Quality of life questionnaire with assessment of the Karnofsky's index will be completed baseline and every 7 days starting from day 1 of L-arginine or placebo administration thereafter
- Secondary Outcome Measures
Name Time Method Neurological progression-free survival Time with no radiological or symptomatic progression counted from the first of radiation therapy until the day of first documented neurological progression or date of death from any cause, whichever came first, assessed up to 50 months The investigators will follow the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines for imaging (CT and MRI) response evaluation based on measurable disease, assessed up to 50 months
Imaging response One month after the last day of radiation and one month after the first response assessment The investigators will follow the R.E.C.I.S.T. criteria for imaging and overall response evaluation