- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03323424
Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers (IRAM)
Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers (IRAM)
Study Overview
Status
Intervention / Treatment
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.
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Albi, France, 81000
- Clinique Claude Bernard
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Dechy, France, 59507
- Centre Leonard de Vinci
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Saint-Grégoire, France, 35760
- Centre Hospitalier Privé Saint Grégoire
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Saint-Priest-en-Jarez, France, 42270
- institut de cancérologie Lucien Neuwirth
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Saint-Priest-en-Jarez, France, 42270
- CHU de St-Etienne
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Valence, France, 26000
- Centre Marie Curie
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Systemic treatment + Stereotactic Body Radio-Therapy (SBRT)
Patients with metastatic breast, colorectal or head or neck cancers and corresponding with the inclusion criteria will receive a systemic treatment, according to the usual practice, but also a Stereotactic Body Radio-Therapy (SBRT).
|
According to the usual practice, patients will receive their systemic treatment, composed of :
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. |
Active Comparator: Systemic treatment
Patients with metastatic breast, colorectal or head or neck cancers and corresponding with the inclusion criteria will receive a systemic treatment, according to the usual practice.
|
According to the usual practice, patients will receive their systemic treatment, composed of :
If progression occurs before the 6th cycles, patients could receive a different line of treatment, according to the usual practice. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Survival rate without progression for patients with metastatic breast cancer
Time Frame: 18 months
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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.
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18 months
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Survival rate without progression for metastatic head and neck cancer
Time Frame: 6 months
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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.
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6 months
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Survival rate without progression for patients with metastatic colorectal cancer
Time Frame: 9 months
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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.
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9 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response rate on predetermined metastatic abscopal sites
Time Frame: 3 months
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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.
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3 months
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Response rate on the irradiated site
Time Frame: 3 months
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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.
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3 months
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Progression-free survival (PFS)
Time Frame: 5 years
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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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5 years
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Overall survival (OS)
Time Frame: 5 years
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The OS will be reported at 5 years after the beginning of the systemic treatment.
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5 years
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Toxicity of the treatments combination
Time Frame: 6 cycles
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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.
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6 cycles
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Toxicity of the treatments combination
Time Frame: 5 years
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Sub-group analysis will be performed following the 3 binary stratification criteria: total number of metastasis, localization of the irradiated metastasis and irradiated volume.
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5 years
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2017-0301
- 2017-A02043-50 (Other Identifier: ANSM)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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