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Completed

NCT Number: NCT02844387

Supplementation of L-arginine in Patients With Non-resectable Brain Metastases

This study evaluates the nutritional supplement arginine as supportive measure for patients with unresectable metastatic brain tumors that receive radiation therapy with palliative intent

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Key information

Conditions

Unresectable Multiple Brain Metastases Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

L-arginine hydrochloride solution

Dietary Supplement

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

Other names: L-arginine, Arginine, L-arginine monohydrochloride

Placebo

Other

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

Other names: flavoured drinking water solution

Primary outcomes

  1. Change from baseline of the scoring form NCI CTCAE v3 for detecting and quantifying potential adverse events

    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

    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

  2. Change from baseline of quality of life questionnaire

    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

    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

  3. Change from baseline in signs and symptoms of neurological disease

    Time frame: 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

Secondary outcomes

  1. Imaging response

    Time frame: 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

  2. Neurological progression-free survival

    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

    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

Other outcomes

  1. Intensity of radiation administered

    Time frame: From the first of radiation therapy through study completion, an average of 1 year

    Actual daily and total dose of radiation administered as fractional product of the planned (proposed) daily and total dose of radiation

  2. effects on tumor metabolism by magnetic resonance spectroscopy

    Time frame: 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

  3. Change from baseline in cytokine pattern in serum

    Time frame: Before treatment (baseline), at 4 weeks after the last of treatment and at 8 weeks after the last of treatment

    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] :

  4. Change from baseline in body weight

    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

    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

  5. Progression free survival

    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

    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

  6. Overall survival

    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

    Survival time counted from the day 1 of radiation therapy to death or lost of follow-up, assessed up to 50 months

Sponsors and collaborators

Lead sponsor

Instituto de Oncología Ángel H. Roffo

Other

Registry information

Official study title

Oral L-arginine Supplementation in Patients With Non-resectable Brain Metastases Treated With Radiation Therapy With Palliative Intent

Important dates

Study start
2004
Primary completion
2007
Study completion
2008
First posted
Jul 26, 2016
Registry last updated
Jul 28, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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