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

Instituto de Oncología Ángel H. Roffo

Status and phase: Completed; Phase 2; Phase 1

Conditions: Unresectable Multiple Brain Metastases

Treatments: Other: Placebo; Dietary Supplement: L-arginine hydrochloride solution

Study type: Interventional

Funder types: Other

Identifiers

NCT02844387

LABM-1

Details and patient eligibility

About

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

Full description

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

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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70 participants in 2 patient groups, including a placebo group

Arginine

Experimental group

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

Treatment:

Dietary Supplement: L-arginine hydrochloride solution

Placebo

Placebo Comparator group

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

Treatment:

Other: Placebo