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

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ClinicalTrials.gov Identifier: NCT03323424
Recruitment Status : Withdrawn (No patient enrolled during the authorized period)
First Posted : October 27, 2017
Last Update Posted : January 30, 2020
Sponsor:
Collaborators:
Saint-Louis Hospital, Paris, France
Gustave Roussy, Cancer Campus, Grand Paris
Information provided by (Responsible Party):
Institut de Cancérologie de la Loire

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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Metastatic Colorectal Cancer Metastatic Head and Neck Cancer Radiation: Systemic treatment + Stereotactic Body Radio-Therapy (SBRT) Other: Systemic treatment Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers (IRAM)
Estimated Study Start Date : January 1, 2019
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : February 1, 2026

Resource links provided by the National Library of Medicine


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).
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.


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.
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.





Primary Outcome Measures :
  1. Survival rate without progression for patients with metastatic breast cancer [ Time Frame: 18 months ]
    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.

  2. Survival rate without progression for metastatic head and neck cancer [ Time Frame: 6 months ]
    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.

  3. Survival rate without progression for patients with metastatic colorectal cancer [ Time Frame: 9 months ]
    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.


Secondary Outcome Measures :
  1. Response rate on predetermined metastatic abscopal sites [ Time Frame: 3 months ]
    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.

  2. Response rate on the irradiated site [ Time Frame: 3 months ]
    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.

  3. Progression-free survival (PFS) [ Time Frame: 5 years ]
    The median PFS according to the RECIST v1.1 criteria will be reported at 5 years after the beginning of the systemic treatment.

  4. Overall survival (OS) [ Time Frame: 5 years ]
    The OS will be reported at 5 years after the beginning of the systemic treatment.

  5. Toxicity of the treatments combination [ Time Frame: 6 cycles ]
    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.

  6. Toxicity of the treatments combination [ Time Frame: 5 years ]
    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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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03323424


Locations
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France
Clinique Claude Bernard
Albi, France, 81000
Centre Léonard de Vinci
Dechy, France, 59507
Centre Hospitalier Privé Saint Gregoire
Saint-Grégoire, France, 35760
CHU de St-Etienne
Saint-Priest-en-Jarez, France, 42270
Institut de Cancérologie Lucien Neuwirth
Saint-Priest-en-Jarez, France, 42270
Centre Marie Curie
Valence, France, 26000
Sponsors and Collaborators
Institut de Cancérologie de la Loire
Saint-Louis Hospital, Paris, France
Gustave Roussy, Cancer Campus, Grand Paris
Investigators
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Principal Investigator: Nicolas Magné, PhD Institut de Cancérologie Lucien Neuwirth
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Responsible Party: Institut de Cancérologie de la Loire
ClinicalTrials.gov Identifier: NCT03323424    
Other Study ID Numbers: 2017-0301
2017-A02043-50 ( Other Identifier: ANSM )
First Posted: October 27, 2017    Key Record Dates
Last Update Posted: January 30, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut de Cancérologie de la Loire:
Metastatic cancer
Abscopal effect
Ionizing radiation
Antibody-Dependant Cell Cytotoxicity (ADCC)
Immuno-Radiation effect
Stereotactic Body Radio-Therapy (SBRT)
Targeted therapies
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes