A Phase 1/2 interventional study of L-arginine hydrochloride solution and Placebo in Unresectable Multiple Brain Metastases, sponsored by Instituto de Oncología Ángel H. Roffo. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-07-28.
Sponsored by Instituto de Oncología Ángel H. Roffo · Phase 1/2, Interventional, and Supportive care
This study evaluates the nutritional supplement arginine as supportive measure for patients with unresectable metastatic brain tumors that receive radiation therapy with palliative intent
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
9,617 studies on the registry are indexed under Neoplasms; 2,508 are open to participants now.
This study's enrollment of 70 is above the median of 50 across 7,432 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →Instituto de Oncología Ángel H. Roffo is the lead sponsor of 2 studies on the registry; 1 is open to participants now.
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Patients with pathology-confirmed diagnostic of solid cancer and measurable brain metastases by CT scan and/or MRI
Inclusion Criteria:
Exclusion Criteria:
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
Dietary Supplement: L-arginine hydrochloride solution
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
Other: Placebo
Patients with unresectable brain metastases from solid tumors that are candidates from twice-daily fractionated radiation therapy will be randomized to receive either oral arginine supplementation one-hour prior to each fraction of radiation. Radiation therapy consist in whole-brain treated by two lateral fields to a total dose of 32 Gy in 20 fractions of 1.6 Gy each two times a day with a 6 hours interval between treatments (10 days), followed by a 22.4 Gy boost over the evident lesions with the same fractionation schedule (7 days). The spinal cord dose will be limited to 40 Gy
Also known as: L-arginine, Arginine, L-arginine monohydrochloride
Patients with unresectable brain metastases from solid tumors that are candidates from twice-daily fractionated radiation therapy will be randomized to receive oral placebo one-hour prior to each fraction of radiation. Radiation therapy consist in whole-brain treated by two lateral fields to a total dose of 32 Gy in 20 fractions of 1.6 Gy each two times a day with a 6 hours interval between treatments (10 days), followed by a 22.4 Gy boost over the evident lesions with the same fractionation schedule (7 days). The spinal cord dose will be limited to 40 Gy
Also known as: flavoured drinking water solution
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
Time frame: 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
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
Time frame: 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
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
Time frame: Baseline and at 4 weeks counted from the last day of treatment
Imaging response
The investigators will follow the R.E.C.I.S.T. criteria for imaging and overall response evaluation
Time frame: One month after the last day of radiation and one month after the first response assessment
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 frame: 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
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
Time frame: From the first of radiation therapy through study completion, an average of 1 year
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
Time frame: Before and one hour after the first dose of L-arginine (or placebo) administration without radiation therapy
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 \[5\] :
Time frame: Before treatment (baseline), at 4 weeks after the last of treatment and at 8 weeks after the last of treatment
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
Time frame: 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
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 frame: 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
Overall survival
Survival time counted from the day 1 of radiation therapy to death or lost of follow-up, assessed up to 50 months
Time frame: 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
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Plan to share: Yes
The record gives a start of May 2004, a primary completion of Nov 2007 and a completion of Dec 2008. It does not say whether these dates are actual or estimated.
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This study is completed, as verified in Jul 2016. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Arginine
Instituto de Oncología Ángel H. Roffo