Unresectable Multiple Brain Metastases Clinical Trial
Official title:
Oral L-arginine Supplementation in Patients With Non-resectable Brain Metastases Treated With Radiation Therapy With Palliative Intent
This study evaluates the nutritional supplement arginine as supportive measure for patients with unresectable metastatic brain tumors that receive radiation therapy with palliative intent
| Status | Completed |
| Enrollment | 70 |
| Est. completion date | December 2008 |
| Est. primary completion date | November 2007 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Patients with pathology-confirmed diagnostic of solid cancer and measurable brain
metastases by CT scan and/or MRI Inclusion Criteria: - 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 Exclusion Criteria: - 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. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Supportive Care
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Instituto de Oncología Ángel H. Roffo |
Bode-Böger SM, Böger RH, Galland A, Tsikas D, Frölich JC. L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol. 1998 Nov;46(5):489-97. — View Citation
Castillo L, Beaumier L, Ajami AM, Young VR. Whole body nitric oxide synthesis in healthy men determined from [15N] arginine-to-[15N]citrulline labeling. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11460-5. — View Citation
Cerchietti LC, Bonomi MR, Navigante AH, Castro MA, Cabalar ME, Roth BM. Phase I/II study of selective cyclooxygenase-2 inhibitor celecoxib as a radiation sensitizer in patients with unresectable brain metastases. J Neurooncol. 2005 Jan;71(1):73-81. — View Citation
Cho-Chung YS, Clair T, Bodwin JS, Berghoffer B. Growth arrest and morphological change of human breast cancer cells by dibutyryl cyclic AMP and L-arginine. Science. 1981 Oct 2;214(4516):77-9. — View Citation
Kang K, Shu XL, Zhong JX, Yu TT. Effect of L-arginine on immune function: a meta-analysis. Asia Pac J Clin Nutr. 2014;23(3):351-9. doi: 10.6133/apjcn.2014.23.3.09. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Intensity of radiation administered | Actual daily and total dose of radiation administered as fractional product of the planned (proposed) daily and total dose of radiation | From the first of radiation therapy through study completion, an average of 1 year | No |
| Other | effects on tumor metabolism by magnetic resonance spectroscopy | Before and one hour after the first dose of L-arginine (or placebo) administration without radiation therapy | Before and one hour after the first dose of L-arginine (or placebo) administration without radiation therapy | No |
| Other | Change from baseline in cytokine pattern in serum | The investigators will determine levels of circulating (serum) cytokines in a sub-group of patients from both arms to determine immune effects of L-arginine. Comments [5] : |
Before treatment (baseline), at 4 weeks after the last of treatment and at 8 weeks after the last of treatment | No |
| Other | Change from baseline in body weight | Body weight (kg) will be determined baseline and every 7 days starting from day 1 of L-arginine or placebo administration thereafter. The reported value will be number of patients with change of 10% or higher in any value at any time point from baseline | 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 | No |
| Other | Progression free survival | 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 | Time with no radiological or symptomatic progression in any site of disease counted from the first of radiation therapy until the day of first documented disease progression or date of death from any cause, whichever came first, assessed up to 50 months | No |
| Other | Overall survival | Survival time counted from the day 1 of radiation therapy to death or lost of follow-up, assessed up to 50 months | Survival time counted from the first of radiation therapy until the date of death from any cause or lost of follow-up, assessed up to 50 months | No |
| Primary | Change from baseline of the scoring form NCI CTCAE v3 for detecting and quantifying potential adverse events | 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 | 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 | Yes |
| Primary | Change from baseline of quality of life questionnaire | 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 | 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 | No |
| Primary | Change from baseline in signs and symptoms of neurological disease | 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 | Baseline and at 4 weeks counted from the last day of treatment | No |
| Secondary | Imaging response | The investigators will follow the R.E.C.I.S.T. criteria for imaging and overall response evaluation | One month after the last day of radiation and one month after the first response assessment | No |
| Secondary | Neurological progression-free survival | 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 | 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 | No |