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

NCT03323424

Description:

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.

Related Conditions:
  • Breast Adenocarcinoma
  • Colorectal Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 2017-0301
  • SECONDARY ID: 2017-A02043-50
  • NCT ID: NCT03323424

Conditions

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

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Systemic treatment + Stereotactic Body Radio-Therapy (SBRT)ExperimentalPatients 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).
    Systemic treatmentActive ComparatorPatients 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.

      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
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Survival rate without progression for patients with metastatic breast cancer
      Time Frame:18 months
      Safety Issue:
      Description: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.

      Secondary Outcome Measures

      Measure:Response rate on predetermined metastatic abscopal sites
      Time Frame:3 months
      Safety Issue:
      Description: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.
      Measure:Response rate on the irradiated site
      Time Frame:3 months
      Safety Issue:
      Description: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.
      Measure:Progression-free survival (PFS)
      Time Frame:5 years
      Safety Issue:
      Description:The median PFS according to the RECIST v1.1 criteria will be reported at 5 years after the beginning of the systemic treatment.
      Measure:Overall survival (OS)
      Time Frame:5 years
      Safety Issue:
      Description:The OS will be reported at 5 years after the beginning of the systemic treatment.
      Measure:Toxicity of the treatments combination
      Time Frame:6 cycles
      Safety Issue:
      Description: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.
      Measure:Toxicity of the treatments combination
      Time Frame:5 years
      Safety Issue:
      Description:Sub-group analysis will be performed following the 3 binary stratification criteria: total number of metastasis, localization of the irradiated metastasis and irradiated volume.

      Details

      Phase:Phase 2
      Primary Purpose:Interventional
      Overall Status:Not yet recruiting
      Lead Sponsor:Institut de Cancérologie de la Loire

      Trial Keywords

      • Metastatic cancer
      • Abscopal effect
      • Ionizing radiation
      • Antibody-Dependant Cell Cytotoxicity (ADCC)
      • Immuno-Radiation effect
      • Stereotactic Body Radio-Therapy (SBRT)
      • Targeted therapies

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