Metastatic Breast CancerPhase 2IRAMNCT03323424
Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers
A Phase 2 study testing Systemic treatment + Stereotactic Body Radio-Therapy (SBRT) and Systemic treatment in people with Metastatic Breast Cancer and Metastatic Colorectal Cancer, run by Institut de Cancérologie de la Loire at 6 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer, Metastatic Colorectal Cancer, Metastatic Head and Neck Cancer
- What is being tested?
- Systemic treatment + Stereotactic Body Radio-Therapy (SBRT) and Systemic treatment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 6 sitesFrance
- Study dates
- 1 Jan 2019to 1 Feb 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
France6 sites
Clinique Claude Bernard
Albi, 81000
Centre Léonard de Vinci
Dechy, 59507
Centre Hospitalier Privé Saint Gregoire
Saint-Grégoire, 35760
CHU de St-Etienne
Saint-Priest-en-Jarez, 42270
Institut de Cancérologie Lucien Neuwirth
Saint-Priest-en-Jarez, 42270
Centre Marie Curie
Valence, 26000
About this study
Official title: Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers (IRAM)
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.
Read the 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.
- Being tested
- Systemic treatment + Stereotactic Body Radio-Therapy (SBRT), Systemic treatment
- Keywords
- Metastatic cancer, Abscopal effect, Ionizing radiation, Antibody-Dependant Cell Cytotoxicity (ADCC), Immuno-Radiation effect, Stereotactic Body Radio-Therapy (SBRT), Targeted therapies
- Medical subject headings
- Breast Neoplasms, Colorectal Neoplasms, Head and Neck Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Systemic treatment + Stereotactic Body Radio-Therapy (SBRT)Radiation
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.
Systemic treatmentOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Systemic treatment + Stereotactic Body Radio-Therapy (SBRT) | Experimental | 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). Receives: Radiation: Systemic treatment + Stereotactic Body Radio-Therapy (SBRT) |
| Systemic treatment | Active comparator | 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. Receives: Other: Systemic treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 months
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.
Measured: 6 months
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.
Measured: 9 months
Secondary outcomes (6)
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.
Measured: 3 months
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.
Measured: 3 months
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.
Measured: 5 years
Overall survival (OS)
The OS will be reported at 5 years after the beginning of the systemic treatment.
Measured: 5 years
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.
Measured: 6 cycles
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.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2017
- Study start1 Jan 2019 (estimated)
- Primary completion1 Feb 2021 (estimated)
- Study completion1 Feb 2026 (estimated)
Why it stopped: No patient enrolled during the authorized period
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut de Cancérologie de la Loire
- Sponsor type
- University, hospital or other
- Collaborators
- Saint-Louis Hospital, Paris, France, Gustave Roussy, Cancer Campus, Grand Paris
- Responsible party
- Sponsor
- Investigators
- Nicolas Magné, PhD, Principal investigator, Institut de Cancérologie Lucien Neuwirth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03323424
- Sponsor's protocol ID
- 2017-0301
- Other IDs
- 2017-A02043-50
- Acronym
- IRAM
- Status last verified
- Jan 2020
- First submitted
- 24 Oct 2017
- Last updated
- 30 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial Assessing the Efficacy of Immuno-Radiation Abscopal Effect in Patients With Metastatic Cancers (IRAM)
- ClinicalTrials.gov ID
- NCT03323424
- Acronym / sponsor ID
- IRAM / 2017-0301
- Keywords
- Metastatic cancer, Abscopal effect, Ionizing radiation, Antibody-Dependant Cell Cytotoxicity (ADCC), Immuno-Radiation effect, Stereotactic Body Radio-Therapy (SBRT), Targeted therapies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No patient enrolled during the authorized period
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Institut de Cancérologie de la LoireUniversity, hospital or other
- Collaborators
- Saint-Louis Hospital, Paris, France, Gustave Roussy, Cancer Campus, Grand Paris
- Study start
- 1 Jan 2019 (estimated)
- Primary completion
- 1 Feb 2021 (estimated)
- Study completion
- 1 Feb 2026 (estimated)
- First posted
- 27 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Systemic treatment + Stereotactic Body Radio-Therapy (SBRT) | Experimental | Radiation: 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). |
| Systemic treatment | Active comparator | Other: Systemic treatmentPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Radiation | Systemic treatment + Stereotactic Body Radio-Therapy (SBRT) |
| Systemic treatmentAccording 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. | Other | Systemic treatment |
Primary outcome
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.
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.
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.
6 secondary outcomes
Response rate on predetermined metastatic abscopal sites
Time frame: 3 months
Response rate on the irradiated site
Time frame: 3 months
Progression-free survival (PFS)
Time frame: 5 years
Overall survival (OS)
Time frame: 5 years
Toxicity of the treatments combination
Time frame: 6 cycles
Toxicity of the treatments combination
Time frame: 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolas Magné, PhD principal investigator
Institut de Cancérologie Lucien Neuwirth
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Systemic treatment + Stereotactic Body Radio-Therapy (SBRT) and Systemic treatment in people with Metastatic Breast Cancer and Metastatic Colorectal Cancer, run by Institut de Cancérologie de la Loire at 6 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 30 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival rate without progression for patients with metastatic breast cancer (time frame: 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2020.