FMISO-PET in Brain Tumors and SCS Effect

NCT01868906 | Terminated Phase 2

• 3 other identifiers: TC-FMISO-PET-06-14132009-015852-11PI 06/1413, PI 12/02940
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of this study is to assess, with 18F-FMISO PET, hypoxia in high grade gliomas and changes by spinal cord stimulation in a subset of patients. Additionally, the potential correlation with pathological, imaging and clinical parameters will be analyzed.

Conditions

Malignant Glioma

Keywords

Anaplastic Astrocytoma; Brain Tumors; Cancer Imaging; Fluoromisonidazole; FMISO PET; Glioblastoma; High Grade Glioma; Hypoxia Modification; Positron Emission Tomography; Radiation-Sensitizing Agents; Spinal Cord Stimulation; Tumor Hypoxia Measurement

Outcome Measures

Primary Outcomes (2)

• Tumor hypoxia measurement using 18F-FMISO-PET (hypoxic volume and tumor/muscle ratio). Baseline measurement.

  Tumor hypoxia will be measured in 20 patients with HGG using 18F-FMISO-PET: after biopsy or surgery and before the commencement of radio-chemotherapy. It will be assessed the prevalence and extent of significant hypoxia in HGG.

  18F-FMISO-PET between 1 and 3 weeks before the commencement of radio-chemotherapy

• Change from baseline tumor hypoxia using 18F-FMISO-PET (hypoxic volume and tumor/muscle ratio) during SCS.

  A subset of 10 patients will undergo a second 18F-FMISO-PET study during spinal cord stimulation to evaluate changes by SCS between 1 and 7 days after the first 18F-FMISO-PET study (and before the commencement of radio-chemotherapy).

  2nd 18F-FMISO-PET between 1 and 7 days after the 1st 18F-FMISO-PET

Secondary Outcomes (7)

• Correlation between 18F-FMISO-PET values and pathological tumor parameters

  Week 0 (at the commencement of radio-chemotherapy).

• Correlation with Karnofsky scale.

  At 0, 2 and 9 months after the commencement of the radio-chemotherapy.

• Correlation with the ECOG (Eastern Cooperative Oncology Group) performance status scale

  At 0, 2 and 9 months after the commencement of the radio-chemotherapy

• Correlation with the Quality of Life Questionnaire QLQ-C30 (EORTC)

  At 0, 2 and 9 months after the commencement of the radio-chemotherapy.

• Overall survival.

  At 9 months after the commencement of the radio-chemotherapy.

Other Outcomes (2)

• Blood flow in carotid and middle cerebral arteries

  Between 1 and 3 weeks before the commencement of radio-chemotherapy

• Facial and supraciliar infrared emission

  Between 1 and 3 weeks before the commencement of radio-chemotherapy

Study Arms (2)

Arm-A: 18F-FMISO-PET without SCS

OTHER

One 18F-FMISO-PET study for assessment of tumor hypoxia before radiotherapy and Temozolomide, without spinal cord stimulation.

Drug: 18F-FMISO; Procedure: PET without SCS; Radiation: Radiotherapy; Drug: Temozolomide

Arm-B: 18F-FMISO-PET without/with SCS

OTHER

Two 18F-FMISO-PET studies for assessment of tumor hypoxia before radiotherapy and Temozolomide: one "without" and one "with" spinal cord stimulation

Drug: 18F-FMISO; Procedure: PET without SCS; Device: SCS; Procedure: PET without/with SCS; Radiation: Radiotherapy; Drug: Temozolomide

Interventions

18F-FMISO DRUG

18F-FMISO-PET scanning, for tumor hypoxia assessment before radio-chemotherapy.

Also known as: Fluoromisonidazole, FMISO

Arm-A: 18F-FMISO-PET without SCS; Arm-B: 18F-FMISO-PET without/with SCS

PET without SCS PROCEDURE

PET-scanning using 18F-fluoromisonidazole without SCS

Also known as: Positron emission tomography scanning

Arm-A: 18F-FMISO-PET without SCS; Arm-B: 18F-FMISO-PET without/with SCS

SCS DEVICE

Electrical stimulation of spinal cord, minimally invasive neurosurgical technique used to treat refractory pain and ischemic syndromes.

Also known as: Electrical Neurostimulation, Spinal Cord Stimulation

Arm-B: 18F-FMISO-PET without/with SCS

PET without/with SCS PROCEDURE

Second PET-scanning using 18F-fluoromisonidazole: without/with SCS

Also known as: Positron emission tomography scanning

Arm-B: 18F-FMISO-PET without/with SCS

Radiotherapy RADIATION

Standard radiation therapy

Also known as: Radiation therapy

Arm-A: 18F-FMISO-PET without SCS; Arm-B: 18F-FMISO-PET without/with SCS

Temozolomide DRUG

Standard treatment with concurrent and adjuvant Temozolomide.

Also known as: Temodar, Temodal, Temcad

Arm-A: 18F-FMISO-PET without SCS; Arm-B: 18F-FMISO-PET without/with SCS

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with pathologically confirmed (first presentation or relapsed) high grade glioma (Grade III or Grade IV according WHO criteria) proposed for radical treatment with 3D radiotherapy and temozolomide.
• Patients 18-75 years old.
• Karnofsky \>= 60% and ECOG =\< 2.
• Signed informed consent.

You may not qualify if:

• Clinical or psychological contraindications to fly (if 18F-FMISO-PET is realized in Madrid) or to SCS-placement (only for this subset).
• Pregnant or breastfeeding women and women of fertile age who are not using a safe contraceptive method or do not intend to use one during the trial. Safe contraceptive methods are oral or parenteral contraceptive treatments or barrier methods: masculine or feminine condom, diaphragm and/or intrauterine device (IUD) or withdrawal over the course of the study.
• Serious co-existing or concurrent illness, including any of the following: uncontrolled or severe infection, heart, liver or kidney disease
• Lung thromboembolism.
• Another malignancy in the last 5 years other than basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• Patients with life expectancy \<3 months.
• Patients with any of the following: creatinine \> 2 mg/dl, neutrophils \<1.5 \* 10\^9/L, platelets \<100 \* 10\^9/L or hemoglobin \<8.5 g/dL.
• Contraindications to receive radiotherapy or chemotherapy Clinical or psychological contraindications for placement of spinal cord stimulation devices (only for that specific subset of patients).
• Patients who are unable or unwilling to meet the protocol study.

Sponsors & Collaborators

• Bernardino Clavo, MD, PhD: lead
• Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid: collaborator
• Instituto de Salud Carlos III: collaborator
• Grupo de Investigación Clínica en Oncología Radioterapia: collaborator
• Instituto Canario de Investigación del Cáncer: collaborator
• RSbiomed: collaborator
• Fundación DISA, Canary Islands, Spain: collaborator

Study Sites (2)

Dr. Negrin University Hospital

Las Palmas, 35010, Spain

Location

Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid

Madrid, 28.033, Spain

Location

Related Publications (12)

• Clavo B, Robaina F, Morera J, Ruiz-Egea E, Perez JL, Macias D, Carames MA, Catala L, Hernandez MA, Gunderoth M. Increase of brain tumor oxygenation during cervical spinal cord stimulation. Report of three cases. J Neurosurg. 2002 Jan;96(1 Suppl):94-100. doi: 10.3171/spi.2002.96.1.0094.

  PMID: 11795721 BACKGROUND

• Clavo B, Robaina F, Catala L, Valcarcel B, Morera J, Carames MA, Ruiz-Egea E, Panero F, Lloret M, Hernandez MA. Increased locoregional blood flow in brain tumors after cervical spinal cord stimulation. J Neurosurg. 2003 Jun;98(6):1263-70. doi: 10.3171/jns.2003.98.6.1263.

  PMID: 12816274 BACKGROUND

• Clavo B, Robaina F, Catala L, Perez JL, Lloret M, Carames MA, Morera J, Lopez L, Suarez G, Macias D, Rivero J, Hernandez MA. Effect of cervical spinal cord stimulation on regional blood flow and oxygenation in advanced head and neck tumours. Ann Oncol. 2004 May;15(5):802-7. doi: 10.1093/annonc/mdh189.

  PMID: 15111351 BACKGROUND

• Clavo B, Robaina F, Montz R, Domper M, Carames MA, Morera J, Pinar B, Hernandez MA, Santullano V, Carreras JL. Modification of glucose metabolism in brain tumors by using cervical spinal cord stimulation. J Neurosurg. 2006 Apr;104(4):537-41. doi: 10.3171/jns.2006.104.4.537.

  PMID: 16619657 BACKGROUND

• Robaina F, Clavo B, Catala L, Carames MA, Morera J. Blood flow increase by cervical spinal cord stimulation in middle cerebral and common carotid arteries. Neuromodulation. 2004 Jan;7(1):26-31. doi: 10.1111/j.1525-1403.2004.04003.x.

  PMID: 22151123 BACKGROUND

• Clavo B, Robaina F, Montz R, Carames MA, Otermin E, Carreras JL. Effect of cervical spinal cord stimulation on cerebral glucose metabolism. Neurol Res. 2008 Jul;30(6):652-4. doi: 10.1179/174313208X305373. Epub 2008 May 29.

  PMID: 18513465 BACKGROUND

• Clavo B, Robaina F, Montz R, Carames MA, Lloret M, Ponce P, Hernandez MA, Carreras JL. Modification of glucose metabolism in radiation-induced brain injury areas using cervical spinal cord stimulation. Acta Neurochir (Wien). 2009 Nov;151(11):1419-25. doi: 10.1007/s00701-009-0400-8. Epub 2009 Jun 5.

  PMID: 19499176 BACKGROUND

• Clavo B, Robaina F, Valcarcel B, Catala L, Perez JL, Cabezon A, Jorge IJ, Fiuza D, Hernandez MA, Jover R, Carreras JL. Modification of loco-regional microenvironment in brain tumors by spinal cord stimulation. Implications for radio-chemotherapy. J Neurooncol. 2012 Jan;106(1):177-84. doi: 10.1007/s11060-011-0660-z. Epub 2011 Jul 12.

  PMID: 21748490 BACKGROUND

• Overgaard J. Hypoxic radiosensitization: adored and ignored. J Clin Oncol. 2007 Sep 10;25(26):4066-74. doi: 10.1200/JCO.2007.12.7878.

  PMID: 17827455 BACKGROUND

• Spence AM, Muzi M, Swanson KR, O'Sullivan F, Rockhill JK, Rajendran JG, Adamsen TC, Link JM, Swanson PE, Yagle KJ, Rostomily RC, Silbergeld DL, Krohn KA. Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival. Clin Cancer Res. 2008 May 1;14(9):2623-30. doi: 10.1158/1078-0432.CCR-07-4995.

  PMID: 18451225 BACKGROUND

• Clavo B, Robaina F, Jorge IJ, Cabrera R, Ruiz-Egea E, Szolna A, Otermin E, Llontop P, Carames MA, Santana-Rodriguez N, Sminia P. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation treatment of recurrent high-grade gliomas. Integr Cancer Ther. 2014 Nov;13(6):513-9. doi: 10.1177/1534735414550037. Epub 2014 Sep 15.

  PMID: 25228535 BACKGROUND

• Clavo B, Robaina F, Fiuza D, Ruiz A, Lloret M, Rey-Baltar D, Llontop P, Riveros A, Rivero J, Castaneda F, Quintero S, Santana-Rodriguez N. Predictive value of hypoxia in advanced head and neck cancer after treatment with hyperfractionated radio-chemotherapy and hypoxia modification. Clin Transl Oncol. 2017 Apr;19(4):419-424. doi: 10.1007/s12094-016-1541-x. Epub 2016 Aug 15.

  PMID: 27527617 BACKGROUND

MeSH Terms

Conditions

Glioma; Astrocytoma; Brain Neoplasms; Glioblastoma

Interventions

fluoromisonidazole; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole; Spinal Cord Stimulation; Radiotherapy; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Bernardino Clavo, MD, PhD

  Dr. Negrin University Hospital, Las Palmas

  STUDY CHAIR

• Bernardino Clavo, MD, PhD

  Dr. Negrin University Hospital, Las Palmas

  PRINCIPAL INVESTIGATOR

• Francisco Robaina, MD, PhD

  Dr. Negrin University Hospital, Las Palmas

  PRINCIPAL INVESTIGATOR

• Juan C Alonso, MD, PhD

  Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Radiation Oncologist, MD, PhD

Study Record Dates

• First Submitted: May 24, 2010
• First Posted: June 5, 2013
• Study Start: June 1, 2013
• Primary Completion: September 17, 2017
• Study Completion: September 17, 2017
• Last Updated: August 24, 2018

Record last verified: 2018-08

Locations

ES (2)