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)

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.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Colorectal Cancer; Metastatic Breast Cancer; Metastatic Head and Neck Cancer
• Intervention / Treatment: Radiation: Systemic treatment + Stereotactic Body Radio-Therapy (SBRT); Other: Systemic 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: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Albi, France, 81000
    • Clinique Claude Bernard
  • Dechy, France, 59507
    • Centre Leonard de Vinci
  • Saint-Grégoire, France, 35760
    • Centre Hospitalier Privé Saint Grégoire
  • Saint-Priest-en-Jarez, France, 42270
    • Institut de Cancérologie Lucien Neuwirth
  • Saint-Priest-en-Jarez, France, 42270
    • CHU de St-Etienne
  • Valence, France, 26000
    • Centre Marie Curie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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)

Number of Arms

2

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).	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	5 years
Overall survival (OS)	The OS will be reported at 5 years after the beginning of the systemic treatment.	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.	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.	5 years

Collaborators and Investigators

• Sponsor: Institut de Cancérologie de la Loire
• Collaborators: Saint-Louis Hospital, Paris, France; Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2019
• Primary Completion (Anticipated): February 1, 2021
• Study Completion (Anticipated): February 1, 2026

Study Registration Dates

• First Submitted: October 24, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (Actual): October 27, 2017

Study Record Updates

• Last Update Posted (Actual): January 30, 2020
• Last Update Submitted That Met QC Criteria: January 28, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Metastatic cancer; Targeted therapies; Abscopal effect; Ionizing radiation; Antibody-Dependant Cell Cytotoxicity (ADCC); Immuno-Radiation effect; Stereotactic Body Radio-Therapy (SBRT)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• 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)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No