Clinical trial · Interventional

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

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

NCT02844387CI-TRIAL-00023283completedPhase 1 / Phase 2ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Unresectable Multiple Brain Metastases	—	UNRESOLVED	—

Interventions

Interventions (2)

Intervention	Type	Mapped drug	Match
L-arginine hydrochloride solution	Dietary Supplement	—	UNRESOLVED
Placebo	Other	—	UNRESOLVED

Design

Arms and outcomes

Arms (2)

type
EXPERIMENTAL
label
Arginine
description
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
interventionNames
1. Dietary Supplement: L-arginine hydrochloride solution
type
PLACEBO_COMPARATOR
label
Placebo
description
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
interventionNames
1. Other: Placebo

Primary outcomes (3)

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

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

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.

References

Publications (5)

BACKGROUNDCastillo 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. doi: 10.1073/pnas.93.21.11460. PMID 8876157
BACKGROUNDCho-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. doi: 10.1126/science.6269181. PMID 6269181
BACKGROUNDBode-Boger SM, Boger RH, Galland A, Tsikas D, Frolich JC. L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol. 1998 Nov;46(5):489-97. doi: 10.1046/j.1365-2125.1998.00803.x. PMID 9833603
BACKGROUNDKang 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. PMID 25164444
BACKGROUNDCerchietti 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. doi: 10.1007/s11060-004-9179-x. PMID 15719279