Clinical trial NCT03323424: Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers
Official title: Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers (IRAM)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Metastatic Colorectal Cancer
Metastatic Head and Neck Cancer
Keywords: Metastatic cancer
Abscopal effect
Ionizing radiation
Antibody-Dependant Cell Cytotoxicity (ADCC)
Immuno-Radiation effect
Stereotactic Body Radio-Therapy (SBRT)
Targeted therapies
Lead sponsor: Institut de Cancérologie de la Loire
Sponsor class: OTHER
Collaborators: name: Saint-Louis Hospital, Paris, France
name: Gustave Roussy, Cancer Campus, Grand Paris
First posted: 2017-10-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Patients with a metastatic breast adenocarcinoma HER2+, a metastatic squamous carcinoma of VADS, or a colorectal adenocarcinoma with a wild status for RAS (NRAS and KRAS)
* Patient presenting at least two measurable metastases (according to the RECIST v1.1 criteria):
* At least one eligible to SBRT (hepatic, pulmonary, bone or intra-cranial metastasis, with a diameter between 1 and 4cm)
* At least one non irradiated measurable metastasis
* Performance Status corresponding to 0, 1, or 2
* Realisation of a PET (Positron Emission Tomography)-Scanner and a TAP (Thoraco-AbdominoPelvic)-Scanner 30 days maximum before inclusion
* Informed consent patient
* Patients affiliated to a social security scheme.

Exclusion Criteria:

* Patient presenting a known non-indication or contraindication to the first line treatment administered
* Pregnant or nursing women
* Patient with an another cancer during the 5 last years, excepting basocellular carcinoma, and skin epidermoid carcinoma
* Patient presenting a non-controlled pain linked to the cancer
* Patient presenting a non-controlled hypercalcemia or symptomatic hypercalcemia needing an ongoing use of bisphosphonates or denosumab.
* Patient presenting an inflammatory pathology or active autoimmune pathology or history of.
* Patient having received one or more vaccines during the 4 weeks preceding the beginning of the systemic treatment.
* Patient currently using corticosteroids or other immune-suppressors during the two weeks before inclusion, and any other situation where this kind of treatments could be necessary during the study.
* Patient deprive of liberty or under administrative supervision, patients with an impossible take care supervision for psychological or geographical reasons.
* Stereotactic Body Radio-Therapy (SBRT) must not include metastases localized in the 3 centimeters of the structure previously irradiated.
* Patient presenting serious active comorbidities defined by the protocol.
* Known seropositivity to the HIV

Primary outcomes:
measure: Survival rate without progression for patients with metastatic breast cancer
timeFrame: 18 months
measure: Survival rate without progression for metastatic head and neck cancer
timeFrame: 6 months
measure: Survival rate without progression for patients with metastatic colorectal cancer
timeFrame: 9 months
Secondary outcomes:
measure: Response rate on predetermined metastatic abscopal sites
timeFrame: 3 months
measure: Response rate on the irradiated site
timeFrame: 3 months
measure: Progression-free survival (PFS)
timeFrame: 5 years
measure: Overall survival (OS)
timeFrame: 5 years
measure: Toxicity of the treatments combination
timeFrame: 6 cycles
measure: Toxicity of the treatments combination
timeFrame: 5 years
Other outcomes:
Locations:
city: Albi
country: France
facility: Clinique Claude Bernard
city: Dechy
country: France
facility: Centre Léonard de Vinci
city: Saint-Grégoire
country: France
facility: Centre Hospitalier Privé Saint Gregoire
city: Saint-Priest-en-Jarez
country: France
facility: CHU de St-Etienne
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Valence
country: France
facility: Centre Marie Curie
Study officials:
affiliation: Institut de Cancérologie Lucien Neuwirth
name: Nicolas Magné, PhD
role: PRINCIPAL_INVESTIGATOR
References: