NCT03323424

Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers

Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers (IRAM)

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Institut de Cancérologie de la Loire · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Metastatic Breast Cancer
• Metastatic Colorectal Cancer
• Metastatic Head and Neck Cancer

Interventions

Type	Name	Description
RADIATION	Systemic treatment + Stereotactic Body Radio-Therapy (SBRT)	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.
OTHER	Systemic treatment	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.

Timeline

• Start date: 2019-01-01
• Primary completion: 2021-02-01
• Completion: 2026-02-01
• First posted: 2017-10-27
• Last updated: 2020-01-30

Locations

6 sites across 1 country: France