Back to resultsPhase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers (IRAM)
Primary Purpose
Metastatic Breast Cancer, Metastatic Colorectal Cancer, Metastatic Head and Neck Cancer
Status
Withdrawn
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Systemic treatment + Stereotactic Body Radio-Therapy (SBRT)
Systemic treatment
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Metastatic cancer, Abscopal effect, Ionizing radiation, Antibody-Dependant Cell Cytotoxicity (ADCC), Immuno-Radiation effect, Stereotactic Body Radio-Therapy (SBRT), Targeted therapies
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
Sites / Locations
- Clinique Claude Bernard
- Centre Léonard de Vinci
- Centre Hospitalier Privé Saint Gregoire
- CHU de St-Etienne
- Institut de Cancérologie Lucien Neuwirth
- Centre Marie Curie
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Systemic treatment + Stereotactic Body Radio-Therapy (SBRT)
Systemic treatment
Arm Description
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).
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.
Outcomes
Primary Outcome Measures
Survival rate without progression for patients with metastatic breast cancer
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.
Survival rate without progression for metastatic head and neck cancer
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.
Survival rate without progression for patients with metastatic colorectal cancer
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
Response rate on predetermined metastatic abscopal sites
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.
Response rate on the irradiated site
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.
Progression-free survival (PFS)
The median PFS according to the RECIST v1.1 criteria will be reported at 5 years after the beginning of the systemic treatment.
Overall survival (OS)
The OS will be reported at 5 years after the beginning of the systemic treatment.
Toxicity of the treatments combination
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.
Toxicity of the treatments combination
Sub-group analysis will be performed following the 3 binary stratification criteria: total number of metastasis, localization of the irradiated metastasis and irradiated volume.
Full Information
NCT ID
NCT03323424
First Posted
October 24, 2017
Last Updated
January 28, 2020
Sponsor
Institut de Cancérologie de la Loire
Collaborators
Saint-Louis Hospital, Paris, France, Gustave Roussy, Cancer Campus, Grand Paris
1. Study Identification
Unique Protocol Identification Number
NCT03323424
Brief Title
Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers
Acronym
IRAM
Official Title
Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers (IRAM)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Withdrawn
Why Stopped
No patient enrolled during the authorized period
Study Start Date
January 1, 2019 (Anticipated)
Primary Completion Date
February 1, 2021 (Anticipated)
Study Completion Date
February 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut de Cancérologie de la Loire
Collaborators
Saint-Louis Hospital, Paris, France, Gustave Roussy, Cancer Campus, Grand Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Systemic treatment + Stereotactic Body Radio-Therapy (SBRT)
Arm Type
Experimental
Arm Description
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).
Arm Title
Systemic treatment
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Systemic treatment + Stereotactic Body Radio-Therapy (SBRT)
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Systemic treatment
Intervention Description
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 Measure Information:
Title
Survival rate without progression for patients with metastatic breast cancer
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.
Time Frame
18 months
Title
Survival rate without progression for metastatic head and neck cancer
Description
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.
Time Frame
6 months
Title
Survival rate without progression for patients with metastatic colorectal cancer
Description
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.
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Response rate on predetermined metastatic abscopal sites
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.
Time Frame
3 months
Title
Response rate on the irradiated site
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.
Time Frame
3 months
Title
Progression-free survival (PFS)
Description
The median PFS according to the RECIST v1.1 criteria will be reported at 5 years after the beginning of the systemic treatment.
Time Frame
5 years
Title
Overall survival (OS)
Description
The OS will be reported at 5 years after the beginning of the systemic treatment.
Time Frame
5 years
Title
Toxicity of the treatments combination
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.
Time Frame
6 cycles
Title
Toxicity of the treatments combination
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.
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolas Magné, PhD
Organizational Affiliation
Institut de Cancérologie Lucien Neuwirth
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinique Claude Bernard
City
Albi
ZIP/Postal Code
81000
Country
France
Facility Name
Centre Léonard de Vinci
City
Dechy
ZIP/Postal Code
59507
Country
France
Facility Name
Centre Hospitalier Privé Saint Gregoire
City
Saint-Grégoire
ZIP/Postal Code
35760
Country
France
Facility Name
CHU de St-Etienne
City
Saint-Priest-en-Jarez
ZIP/Postal Code
42270
Country
France
Facility Name
Institut de Cancérologie Lucien Neuwirth
City
Saint-Priest-en-Jarez
ZIP/Postal Code
42270
Country
France
Facility Name
Centre Marie Curie
City
Valence
ZIP/Postal Code
26000
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers
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