Clinical trial NCT04854213: PRELUDE-1 (Prospective Evaluation of Radiotherapy-induced Biologic Effects in Colorectal Cancer Oligometastatic Patients with LUng-limited Disease: Evolution of Cancer Genetics and Regulatory Immune Cells)
Official title: PRELUDE-1 (Prospective Evaluation of Radiotherapy-induced Biologic Effects in Colorectal Cancer Oligometastatic Patients with LUng-limited Disease: Evolution of Cancer Genetics and Regulatory Immune Cells)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Cancer Metastatic
Keywords: SBRT
liquid biopsy
metastatic disease
cancer genetics
NGS
omCRC
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2021-04-22
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: PRELUDE-1 study is a pilot intervention trial that aims to describe the immunologic and genetic evolutions induced by stereotactic body radiationtherapy (SBRT) treatment in oligometastatic Colorectal Cancer (omCRC) patients with two-three nodules lung-limited disease.

Detailed description: PRELUDE-1 study is a monocentric pilot interventional trial. The study concerns all patients enrolled with a diagnosis of oligometastatic Colorectal Cancer (omCRC) with two-three nodules lung-limited disease and treated with SBRT technique. SBRT will be delivered according to a risk-adapted protocol.

Tumor genetic background will be assessed on primary FFPE (Formalin Fixed Paraffin Embedded) tissues. Liquid biopsy will be done on blood samples collected before radiotherapy (RT) start and after 40 days to monitor tumor DNA evolution. The most direct method to assess cancer genetics relies on sampling of tumor DNA and its characterization through whole genome sequencing techniques (NGS, Next Generation Sequencing).

The study will last 48 months, divides as follow: 24 months of enrollment phase and up to 24 months of follow-up. Follow-up will be performed on the 40th day after the end of radiation treatment and then every 3 months until progression.

Eligibility criteria: Inclusion Criteria:

* Age \<80 years
* Cytological or histological diagnosis of colorectal adenocarcinoma
* Two or three asymptomatic lung nodules smaller than 25 mm
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Available Formalin Fixed Paraffin Embedded (FFPE) of resected primary tumor
* Negative pregnancy test for all potentially childbearing women
* Patient candidates to SBRT

Exclusion Criteria:

* Previous systemic anti-tumor treatments (allowed treatment with capecitabine or fluorouracil and radiotherapy in the neoadjuvant setting of rectal tumors with therapy terminated at least 6 months before)
* Neutrophils \<2000/mm³ or platelets \<100.000/mm³ or hemoglobin \<9 g/dl; serum creatinine level\> 1.5 times the maximum normal value; GOT and/or GPT \>5 times the maximum normal value and/or bilirubin level \>3 times the maximum normal value
* Previous or concomitant malignant neoplasms (excluding basal or spinocellular cutaneous carcinoma or in situ carcinoma of the uterine cervix)
* Active or uncontrolled infections
* Other concomitant uncontrolled diseases or conditions contraindicating the study drugs at clinician evaluation
* Presence of brain metastases
* Refusal or inability to provide informed consent
* Impossibility to guarantee follow-up

Primary outcomes:
measure: To assess the efficacy of SBRT in inducing a regressive genetic trajectory of KRAS gene (evaluated by NGS technique) after SBRT treatment.
timeFrame: 40 days after the end of RT
Secondary outcomes:
measure: To evaluate the response according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, version 1.1 including any eventual abscopal effect.
timeFrame: Up to 24 months after the end of RT
measure: To evaluate the responses' duration (measured from the time of documented objective response until documented tumor progression).
timeFrame: Up to 24 months after the end of RT
measure: To evaluate the progression-free (PFS) survival (from the data of treatment start untill progression).
timeFrame: Up to 24 months after the end of RT
measure: The toxicity, which will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute, version 5.0, November 27, 2017.
timeFrame: Up to 24 months after the end of RT
measure: Tumor immune microenvironment in primary tumour
timeFrame: 40 days after the end of RT
measure: Metabolic response (exploratory studies)
timeFrame: 40 days after the end of RT
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori - Fondazione G. Pascale
Study officials:
affiliation: National Cancer Institute of Naples
name: Paolo Muto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute of Naples
name: Alessandro Ottaiano, MD
role: PRINCIPAL_INVESTIGATOR
References: