FMISO-PET in Brain Tumors and SCS Effect

Malignant Glioma Clinical Trial

— FMISOPETSCS  

Official title:

Positron Emission Tomography With Fluoro-misonidazole (PET-FMISO) in High Grade Gliomas: Assessment of Tumor Hypoxia and Effect of Spinal Cord Stimulation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01868906
• Other study ID #: TC-FMISO-PET-06-1413
• Secondary ID: 2009-015852-11PI
• Status: Terminated
• Phase: Phase 2
• Start date: June 2013
• Est. completion date: September 17, 2017

Study information

• Verified date: August 2018
• Source: Dr. Negrin University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Tumour ischaemia-hypoxia decreases the efficacy of radio-chemotherapy. Polarographic probe (and some 18F-FMISO-PET) studies have demonstrated prognostic value. Additionally hypoxia modification may increase survival. However, in high grade gliomas (HGG) there are not well established methods to evaluate and modify tumor hypoxia. We have previously described how spinal cord stimulation (SCS) can modify oxygenation, blood flow and metabolism in malignant gliomas. The aim of this study is to assess with 18F-FMISO PET: hypoxia in HGG and changes by spinal cord stimulation in a subset of patients. Additionally, the potential correlation with pathological, imaging and clinical parameters will be analyzed.

18F-FMISO PET will be performed in 20 patients with diagnosis of HGG: after surgery/biopsy and before radical treatment with 3D radiotherapy and temozolomide. A subset of 10 patients undergo two studies with 18F- FMISO-PET (one with SCS "off" and one with SCS "on"). In these patients, SCS will be connected from 1 hour before to 1 hour after each radiotherapy session, and in the day-time during the days of adjuvant temozolomide.

18F-FMISO PET results will not be taking into account for patient management. Patients will be followed at least until the end of adjuvant temozolomide (6 months after the end of concurrent radiochemotherapy).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: September 17, 2017
• Est. primary completion date: September 17, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• Patients who do not meet all the inclusion criteria.

Related Conditions & MeSH terms

• Glioma
• Malignant Glioma

Intervention

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

Procedure:
• PET without SCS
PET-scanning using 18F-fluoromisonidazole without SCS

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

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

Radiation:
• Radiotherapy
Standard radiation therapy

Drug:
• Temozolomide
Standard treatment with concurrent and adjuvant Temozolomide.

Locations

Country	Name	City	State
Spain	Dr. Negrin University Hospital	Las Palmas
Spain	Instituto Tecnologico Servicios Sanitarios, in MD Anderson Cancer Center, Madrid	Madrid

Sponsors (7)

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

Country where clinical trial is conducted

Spain, 

References & Publications (12)

Clavo B, Robaina F, Catalá L, Pérez JL, Lloret M, Caramés MA, Morera J, López L, Suárez G, Macías D, Rivero J, Hernández 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. — View Citation

Clavo B, Robaina F, Catalá L, Valcárcel B, Morera J, Caramés MA, Ruiz-Egea E, Panero F, Lloret M, Hernández MA. Increased locoregional blood flow in brain tumors after cervical spinal cord stimulation. J Neurosurg. 2003 Jun;98(6):1263-70. — View Citation

Clavo B, Robaina F, Fiuza D, Ruiz A, Lloret M, Rey-Baltar D, Llontop P, Riveros A, Rivero J, Castañeda F, Quintero S, Santana-Rodríguez 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. — View Citation

Clavo B, Robaina F, Jorge IJ, Cabrera R, Ruiz-Egea E, Szolna A, Otermin E, Llontop P, Carames MA, Santana-Rodríguez 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Clavo B, Robaina F, Morera J, Ruiz-Egea E, Pérez JL, Macías D, Caramés MA, Catalá L, Hernández MA, Günderoth M. Increase of brain tumor oxygenation during cervical spinal cord stimulation. Report of three cases. J Neurosurg. 2002 Jan;96(1 Suppl):94-100. — View Citation

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. — View Citation

Overgaard J. Hypoxic radiosensitization: adored and ignored. J Clin Oncol. 2007 Sep 10;25(26):4066-74. Review. — View Citation

Robaina F, Clavo B, Catalá L, Caramés MÁ, 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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood flow in carotid and middle cerebral arteries	To analyze the correlation between 18F-FMISO-PET values and blood flow in carotid and middle cerebral arteries (assessed before the commencement of radio-chemotherapy) using Doppler measurements.	Between 1 and 3 weeks before the commencement of radio-chemotherapy
Other	Facial and supraciliar infrared emission	To analyze the correlation between 18F-FMISO-PET values and facial and supraciliar infrared emission (assessed by digital thermography)	Between 1 and 3 weeks before the commencement of radio-chemotherapy
Primary	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
Primary	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	Correlation between 18F-FMISO-PET values and pathological tumor parameters	To analyze the correlation of 18F-FMISO-PET with histological parameters and tumor expression of: CD31 (vascular density), VEGF (vascular endothelial growth factor) and VEGFR (angiogenesis), EGFR (epidermal growth factor receptor), Ki-67 (proliferation index) and hypoxic markers	Week 0 (at the commencement of radio-chemotherapy).
Secondary	Correlation with Karnofsky scale.	To analyze the correlation with performance status using the Karnofsky scale.	At 0, 2 and 9 months after the commencement of the radio-chemotherapy.
Secondary	Correlation with the ECOG (Eastern Cooperative Oncology Group) performance status scale	To analyze the correlation with performance status using the ECOG (WHO) scale.	At 0, 2 and 9 months after the commencement of the radio-chemotherapy
Secondary	Correlation with the Quality of Life Questionnaire QLQ-C30 (EORTC)	To analyze the correlation with quality of life using the QLQ-C30 (EORTC) questionnaire.	At 0, 2 and 9 months after the commencement of the radio-chemotherapy.
Secondary	Overall survival.	To analyze the correlation with overall survival.	At 9 months after the commencement of the radio-chemotherapy.
Secondary	Radiological response to treatment	To analyze the correlation between 18F-FMISO-PET values and radiological response to treatment	9 months after the commencement of radio-chemotherapy
Secondary	Radiological location of tumor relapse or progression	To analyze the correlation between 18F-FMISO-PET values and the radiological location of tumor relapse or progression	9 months after the commencement of radio-chemotherapy