Tumour and HEalthy Tissues DOse-response and Radiosensitivity Assay

Sarcoma Clinical Trial

— THEODORA  

Official title:

Evaluation of Individual Radiosensitivity of Cancer Patients to be Treated by Radiotherapy or Radiochemotherapy Per-operative

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02797405
• Other study ID #: ET15-003
• Secondary ID: 2015-A00931-48
• Status: Terminated
• Phase: N/A
• Start date: October 2016
• Est. completion date: March 13, 2020

Study information

• Verified date: March 2020
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

THEODORA is a prospective pilot clinical trial aiming at first to evaluate and validate the predictive value of the A & MS bioassays on tumor control by radiotherapy.

Description:

For that purpose, this project is composed of 3 stages:

• A Calibration stage that will allow to evaluate the correlation between the clinical tumor response parameters (i.e. TV/AP features) and the radiobiological parameters issued from the A/MS bioassays in order to develop a mathematic model defining the UTCR parameter

• A Validation stage in order to assess the validity of A/MS bioassays towards clinical tumour response parameters (i.e. both TV/AP features and UTCR).

• A Precision stage will be performed either to improve the precision of the predictive performance of the A and MS bioassays or to establish a new mathematical model describing the correlation between clinical and radiobiological parameters. The objective of this precision stage will depend of the results of the calibration stage (see below).

This prospective clinical study will be conducted in a population of patients with different tumor types in order to explore a large range of tumor radiosensitivity including sarcomas, rectal carcinoma and esophagus tumor.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 97
• Est. completion date: March 13, 2020
• Est. primary completion date: August 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

I1. Patients (male or female) = 18 years of age. I2. Adult patients with a suspected, non-treated, non-metastatic retroperitoneal or limb soft tissue sarcoma, esophagus cancer or rectum cancer to be treated by pre-operative radiotherapy or radio-chemotherapy I3. At least one measurable lesion as per RECIST 1.1 I4. Documented negative serology tests (HVB, HIV, HVC) I5. PS ECOG 0 to 1 I6. Patient able and willing to provide informed consent. I7. Ability to understand and willingness for follow-up visits. I8. Covered by a medical insurance.

Exclusion Criteria:

E1. Contra-indication to radiotherapy E2. Contra-indication to skin biopsy

Related Conditions & MeSH terms

• Esophageal Neoplasms
• Esophagus Cancer
• Rectal Carcinoma
• Sarcoma

Intervention

Radiation:
• Standard treatment
Sarcoma patients will undergo radiotherapy followed by surgery Rectum cancer patients will undergo radio-chemotherapy followed by surgery Esophagus cancer patients will undergo radio-chemotherapy followed by surgery

Locations

Country	Name	City	State
France	Centre Francois Baclesse	Caen
France	Infirmerie Protestante	Caluire-et-Cuire
France	Centre Georges-François Leclerc	Dijon
France	Centre Léon Bérard	Lyon
France	Hôpital Privé Jean Mermoz	Lyon
France	ICL - Institut de Cancérologie de la Lorraine	Vandœuvre-lès-Nancy
France	Hopital Nord Ouest Villefranche Sur Saone	Villefranche-sur-Saône

Sponsors (1)

Lead Sponsor	Collaborator
Centre Leon Berard

Country where clinical trial is conducted

France, 

References & Publications (29)

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Bodgi L, Granzotto A, Devic C, Vogin G, Lesne A, Bottollier-Depois JF, Victor JM, Maalouf M, Fares G, Foray N. A single formula to describe radiation-induced protein relocalization: towards a mathematical definition of individual radiosensitivity. J Theor Biol. 2013 Sep 21;333:135-45. doi: 10.1016/j.jtbi.2013.05.020. Epub 2013 Jun 2. — View Citation

Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, Byhardt R, Russell AH, Beitler JJ, Spencer S, Asbell SO, Graham MV, Leichman LL. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999 May 5;281(17):1623-7. — View Citation

COPERNIC project investigators, Granzotto A, Benadjaoud MA, Vogin G, Devic C, Ferlazzo ML, Bodgi L, Pereira S, Sonzogni L, Forcheron F, Viau M, Etaix A, Malek K, Mengue-Bindjeme L, Escoffier C, Rouvet I, Zabot MT, Joubert A, Vincent A, Dalla Venezia N, Bourguignon M, Canat EP, d'Hombres A, Thébaud E, Orbach D, Stoppa-Lyonnet D, Radji A, Doré E, Pointreau Y, Bourgier C, Leblond P, Defachelles AS, Lervat C, Guey S, Feuvret L, Gilsoul F, Berger C, Moncharmont C, de Laroche G, Moreau-Claeys MV, Chavaudra N, Combemale P, Biston MC, Malet C, Martel-Lafay I, Laude C, Hau-Desbat NH, Ziouéche A, Tanguy R, Sunyach MP, Racadot S, Pommier P, Claude L, Baleydier F, Fleury B, de Crevoisier R, Simon JM, Verrelle P, Peiffert D, Belkacemi Y, Bourhis J, Lartigau E, Carrie C, De Vathaire F, Eschwege F, Puisieux A, Lagrange JL, Balosso J, Foray N. Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity. Int J Radiat Oncol Biol Phys. 2016 Mar 1;94(3):450-60. doi: 10.1016/j.ijrobp.2015.11.013. Epub 2015 Nov 14. — View Citation

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Fleming FJ, Påhlman L, Monson JR. Neoadjuvant therapy in rectal cancer. Dis Colon Rectum. 2011 Jul;54(7):901-12. doi: 10.1007/DCR.0b013e31820eeb37. Review. — View Citation

Foray N, Colin C, Bourguignon M. 100 years of individual radiosensitivity: how we have forgotten the evidence. Radiology. 2012 Sep;264(3):627-31. doi: 10.1148/radiol.12112560. — View Citation

Gérard A, Buyse M, Nordlinger B, Loygue J, Pène F, Kempf P, Bosset JF, Gignoux M, Arnaud JP, Desaive C, et al. Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC). Ann Surg. 1988 Nov;208(5):606-14. — View Citation

Granzotto A, Joubert A, Viau M, Devic C, Maalouf M, Thomas C, Vogin G, Malek K, Colin C, Balosso J, Foray N. [Individual response to ionising radiation: What predictive assay(s) to choose?]. C R Biol. 2011 Feb;334(2):140-57. doi: 10.1016/j.crvi.2010.12.018. Review. French. — View Citation

Ishikura S, Nihei K, Ohtsu A, Boku N, Hironaka S, Mera K, Muto M, Ogino T, Yoshida S. Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol. 2003 Jul 15;21(14):2697-702. — View Citation

Joubert A, Zimmerman KM, Bencokova Z, Gastaldo J, Chavaudra N, Favaudon V, Arlett CF, Foray N. DNA double-strand break repair defects in syndromes associated with acute radiation response: at least two different assays to predict intrinsic radiosensitivity? Int J Radiat Biol. 2008 Feb;84(2):107-25. doi: 10.1080/09553000701797039. — View Citation

Koshy M, Rich SE, Mohiuddin MM. Improved survival with radiation therapy in high-grade soft tissue sarcomas of the extremities: a SEER analysis. Int J Radiat Oncol Biol Phys. 2010 May 1;77(1):203-9. doi: 10.1016/j.ijrobp.2009.04.051. Epub 2009 Aug 11. — View Citation

Lievens Y, Grau C. Health economics in radiation oncology: introducing the ESTRO HERO project. Radiother Oncol. 2012 Apr;103(1):109-12. doi: 10.1016/j.radonc.2011.12.026. Epub 2012 Feb 8. — View Citation

Morota M, Gomi K, Kozuka T, Chin K, Matsuura M, Oguchi M, Ito H, Yamashita T. Late toxicity after definitive concurrent chemoradiotherapy for thoracic esophageal carcinoma. Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):122-8. doi: 10.1016/j.ijrobp.2008.10.075. Epub 2009 Mar 26. — View Citation

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O'Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P, Wunder J, Kandel R, Goddard K, Sadura A, Pater J, Zee B. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet. 2002 Jun 29;359(9325):2235-41. — View Citation

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Stahl R, Wang T, Lindner LH, Abdel-Rahman S, Santl M, Reiser MF, Issels RD. Comparison of radiological and pathohistological response to neoadjuvant chemotherapy combined with regional hyperthermia (RHT) and study of response dependence on the applied thermal parameters in patients with soft tissue sarcomas (STS). Int J Hyperthermia. 2009 Jun;25(4):289-98. doi: 10.1080/02656730902873616. — View Citation

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* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Calibration of the correlation between the clinical tumor response and the results of A/MS bioassays using tumor samples	The calibration stage will be performed using data from the first 40 patients enrolled. All the potential correlations between the clinical and radiobiological parameters will be tested. The links between clinical tumor response parameters and radiobiological parameters derived from MS/A bioassays using tumor samples.	2.5 years (after 100 patients enrolled )
Primary	Validation of the correlation between the clinical tumor response and the results of A/MS bioassays using tumor samples	The validation stage will be performed using data from the remaining 60 patients enrolled. This stage will assess whether or not the prediction of tumor response derived from the A/MS bioassays fits with the observed tumor response after RT.	2.5 years (after 100 patients enrolled )
Secondary	Validation of the correlation between the healthy tissue response (i.e. AE reported as per CTCAE v4) and the results of MS/A bioassays using skin biopsies		2.5 years (after 100 patients enrolled )