The proposed theory is based on combination of radiation therapy with usual targeted therapies capable of ADCC (Antibody-Dependant Cell Cytotoxicity). This association could enhance in a additive/synergistic way the benefic impact of immune system activation on tumor control. Stereotactic Body Radio-Therapy (SBRT) will be combined with the first line chemotherapy for metastatic breast, colorectal or VADS (upper aerodigestive tract) cancers. The IRAM study objective is to highlight a possible abscopal effect of this combination for metastatic cancer patients.
Nowadays, metastatic cancer treatment is evolving with systemic treatments (target therapies and immunotherapies). Combinations and new therapeutic schemes have recently boosted the interest for an effect called "abscopal". This effect is based on the immune-stimulating effect of high doses ionizing radiations, but also on synergistic association with systemic treatment with immunologic mechanisms. This effect could enhance the tumor local control, but also its distant control. Numerous preclinical evidences as well as some clinical case reports described the abscopal effect. Ongoing clinical studies are investigating with radiotherapy abscopal effect alone, or associated with immunotherapies (anti-CTLA-4, PD-1 or PDL-1). The present study proposes a new association, based on an original biological rational. The proposed theory is based on combination of radiation therapy with usual targeted therapies capable of ADCC (Antibody-Dependant Cell Cytotoxicity). This association could enhance in an additive/synergistic way the benefic impact of immune system activation on tumor control. In the present study, Stereotactic Body Radio-Therapy (SBRT) will be combined to the standard systemic treatment for first line treatment of metastatic breast, colorectal and VADS (upper aerodigestive tract) cancers. Indeed, these treatments have in common the use of target therapies capable of ADCC. The IRAM study objective is to highlight a possible abscopal effect of this combination for metastatic cancer patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
According to the usual practice, patients will receive their systemic treatment, composed of : * Taxane + trastuzumab +pertuzumab for metastatic breast cancers; * FOLFOX or FOLFIRI + cetuximab for metastatic colorectal cancers; * 5FU-Platine + cetuximab for metastatic head and neck cancers; for six cycles and a maintenance of the targeted therapy until progression or unacceptable toxicity. If progression occurs before the 6th cycles, patients could receive a different line of treatment, according to the usual practice. In addition to the systemic treatment, patients randomized into this experimental group will receive a SBRT of 45Gy in 3 fractions for hepatic and pulmonary metastasis, 27Gy in 3 fractions for bone metastasis and 33 Gy in 3 fractions for intra-cranial metastasis.
According to the usual practice, patients will receive their systemic treatment, composed of : * Taxane + trastuzumab +pertuzumab for metastatic breast cancers; * FOLFOX or FOLFIRI + cetuximab for metastatic colorectal cancers; * 5FU-Platine + cetuximab for metastatic head and neck cancers; for six cycles and a maintenance of the targeted therapy until progression or unacceptable toxicity. If progression occurs before the 6th cycles, patients could receive a different line of treatment, according to the usual practice.
Clinique Claude Bernard
Albi, France
Centre Léonard de Vinci
Dechy, France
Centre Hospitalier Privé Saint Gregoire
Saint-Grégoire, France
CHU de St-Etienne
Saint-Priest-en-Jarez, France
Survival rate without progression for patients with metastatic breast cancer
The rate of survival without progression according to the RECIST (v1.1) criteria for patients with metastatic breast cancer will be calculated at 18 months after the beginning of the systemic treatment.
Time frame: 18 months
Survival rate without progression for metastatic head and neck cancer
The rate of survival without progression according to the RECIST (v1.1) criteria for patients with head and neck cancer will be calculated at 6 months after the beginning of the systemic treatment.
Time frame: 6 months
Survival rate without progression for patients with metastatic colorectal cancer
The rate of survival without progression according to the RECIST (v1.1) criteria for patients with colorectal cancer will be calculated at 9 months after the beginning of the systemic treatment.
Time frame: 9 months
Response rate on predetermined metastatic abscopal sites
The response rate on predetermined metastatic abscopal sites will be evaluated at 3 months after the beginning of the systemic treatment according to the RECIST v1.1 criteria.
Time frame: 3 months
Response rate on the irradiated site
The response rate on the irradiated site will be evaluated at 3 months after the beginning of the systemic treatment according to the RECIST v1.1 criteria.
Time frame: 3 months
Progression-free survival (PFS)
The median PFS according to the RECIST v1.1 criteria will be reported at 5 years after the beginning of the systemic treatment.
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Institut de Cancérologie Lucien Neuwirth
Saint-Priest-en-Jarez, France
Centre Marie Curie
Valence, France
Time frame: 5 years
Overall survival (OS)
The OS will be reported at 5 years after the beginning of the systemic treatment.
Time frame: 5 years
Toxicity of the treatments combination
During the first line of systemic treatment (six cycles of treatment maximum), the number and the grade (CTCAE v4.4) of toxicities related to the systemic treatment /Radiation therapy combination will be reported.
Time frame: 6 cycles
Toxicity of the treatments combination
Sub-group analysis will be performed following the 3 binary stratification criteria: total number of metastasis, localization of the irradiated metastasis and irradiated volume.
Time frame: 5 years