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

NCT02844387 | Completed Phase 1

• 1 other identifier: LABM-1
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

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

Conditions

Unresectable Multiple Brain Metastases

Keywords

cancer; brain; arginine; radiation

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Secondary Outcomes (2)

• Imaging response

  One month after the last day of radiation and one month after the first response assessment

• 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

Other Outcomes (6)

• Intensity of radiation administered

  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

• Change from baseline in cytokine pattern in serum

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

Study Arms (2)

Arginine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

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

Also known as: L-arginine, Arginine, L-arginine monohydrochloride

Arginine

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

Also known as: flavoured drinking water solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto de Oncología Ángel H. Roffo: lead

Related Publications (5)

• 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. doi: 10.1073/pnas.93.21.11460.

  PMID: 8876157 BACKGROUND

• 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. doi: 10.1126/science.6269181.

  PMID: 6269181 BACKGROUND

• Bode-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 BACKGROUND

• 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.

  PMID: 25164444 BACKGROUND

• 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. doi: 10.1007/s11060-004-9179-x.

  PMID: 15719279 BACKGROUND

MeSH Terms

Conditions

Neoplasms

Interventions

Arginine; N(alpha)-lauroylarginine ethyl ester

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Alfredo H Navigante, MD, Phd

  Instituto de Oncología Ángel H. Roffo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2016
• First Posted: July 26, 2016
• Study Start: May 1, 2004
• Primary Completion: November 1, 2007
• Study Completion: December 1, 2008
• Last Updated: July 28, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will share