Neo-adjuvant Immunotherapy Master Trial for Localized Cancers
ConditionLocalized Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age12+
SponsorUNICANCER
About this trial
Most cancer treatments are developed without knowing whether the drug's targets are actually present in a patient's tumor or whether the patient is likely to benefit from the treatment. In addition, the immune environment surrounding the tumor changes significantly during the course of the disease, and the body's immune response to cancer tends to become less effective in later stages.
Currently, standard blood tests provide only basic information about a patient's immune, inflammatory, and metabolic systems. These tests do not offer a comprehensive picture of how each person's immune system is functioning. Similarly, traditional tests on tumor samples-which require frozen or preserved tissue and take a long time to process-are not fast enough to guide treatment decisions during clinical trials.
NEOREM is a "Master Protocol" which includes multiple therapeutic sub-protocols testing new immunotherapy strategies. (Immunotherapy is a type of cancer treatment that helps the immune system fight cancer.) Neoadjuvant immunotherapies are treatments given before surgery. Their goals are to shrink the tumor to make it easier to remove, strengthen the immune system's ability to fight cancer, increase the chances of long-term recovery, and reduce the risk of the cancer returning.
This master protocol focuses on cancers that are still localized (have not spread) and aims to personalize treatments based on each patient's individual immuno-biological profile. As a part of this master protocol, a rapid analysis called PORTRAIT-which stands for "Profile in Onco-Immunology for a Rapid Treatment Research Adapted to Immunity and Tumor"-will be performed using fresh blood and tumor samples from each patient. This profiling uses highly sensitive and specific techniques to accurately detect biological markers that can predict how well someone will respond to immunotherapy before surgery.
NEOREM's overall goal is to test new treatment strategies and new methods of selecting patients (using the PORTRAIT immune profiling) to improve the effectiveness of current standard treatments for certain types of cancer while also reducing their side effects.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age≥ 12 years with at least 40kg body weight or otherwise as per specified in sub-protocol.
Prior to the inclusion in the NEOREM master protocol, patients must have signed a written informed consent to baseline PORTRAIT profiling.
When the patient is physically unable to give his/her written consent, a trusted person of his/her choice, independent from the investigator or the sponsor, can confirm in signing the patient's consent.
For patients aged between > 12 and < 18, specific consent from legal tutors should be obtained on top of the minor consent and prior procedures.
Disqualifiers
Cancer patients with advanced stages and/or distant metastasis (unless curable oligometastatic disease). Some sub-protocols could enroll patients with loco-regional (N+) stages amenable to curative intention strategies.
Any life-threatening allergy to one of the experimental products tested in the sub-protocol where the patient is eligible. In case of allergy to contrast media, patient monitoring should be performed with alternate methods (both CT-scan or MRI).
History of life threatening autoimmune/immune mediated inflammatory disease, including but not limited to severe colitis, pneumonitis, Guillain-Barré syndrome, anti-phospholipid syndromes and myocarditis. Patients with a history of auto-immune endocrinopathy (hypo/hyper thyroiditis, type 1 diabetes mellitus, …) and who are stable on hormone replacement therapy are eligible for the study. Patients with a history of vitiligo, alopecia areata, cutaneous psoriasis and grade 1-2 Sjogren syndrome are eligible.
Treatment with systemic long-term immunosuppressive medications unless otherwise specified in the specific therapeutic sub-protocols. Those immunosuppressive drugs must have been stopped at least 4 weeks prior to enrolment. Hormone replacement therapy with physiological doses of hydrocortisone is acceptable.
Trial design
Design model
Single group
Treatments tested in this trial
Each therapeutic NEOREM sub-protocol will mention the description of intervention
DrugEach therapeutic NEOREM sub-protocol will mention the description of intervention
Treatment groups
200 Participants
are divided into 1 treatment groupGroup A: Single Arm immunotherapy in Localized CancersExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
The main objective is to evaluate efficacy of novel treatment strategies to increase the patient population therapeutic index in histology-based or tumor-agnostic/biomarker-driven oncology indications
In the context of NEOREM, increasing the therapeutic index means enhancing the effectiveness of a treatment strategy-measured through efficacy endpoints - as complete pathological response,pCR, defined as the complete absence of viable tumor cells or major pathological response i.e. less than 10% viable tumor cells in the surgical specimen - within patient groups most likely to benefit, while reducing toxicity risks in those unlikely to respond.
Time frame
Through all the NEOREM subprotocols completion and no new subprotocol is designed, an average of 7 years2
The main objective is to evaluate safety of novel treatment strategies to increase the patient population therapeutic index in histology-based or tumor-agnostic/biomarker-driven oncology indications
Safety measurements will include the percentage of patients whose surgery was delayed beyond the planned timeline, due to treatment-related adverse events.
Time frame
Through all the NEOREM subprotocols completion and no new subprotocol is designed, an average of 7 years3
The main objective is to evaluate patient selection criteria to increase the patient population therapeutic index in histology-based or tumor-agnostic/biomarker-driven oncology indications
The sub-protocols may be designed as exploratory or confirmatory trials to validate immune biomarkers for patient selection using PORTRAIT immunoprofiling. PORTRAIT profiling can be generated on from fresh whole blood and fresh tumor biopsies in order to allow for a rapid, sensitive and specific description of each patient's immuno-biological profile.
Time frame
Through all the NEOREM subprotocols completion and no new subprotocol is designed, an average of 7 years Source ClinicalTrials.gov