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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) (PRELUDE-1)

Primary Purpose

Colorectal Cancer Metastatic

Status

Recruiting

Phase

Not Applicable

Locations

Italy

Study Type

Interventional

Intervention

Stereotactic Body Radiation Therapy (SBRT)

About this trial

This is an interventional other trial for Colorectal Cancer Metastatic focused on measuring SBRT, liquid biopsy, metastatic disease, cancer genetics, NGS, omCRC

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Istituto Nazionale Tumori - Fondazione G. PascaleRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Liquid biopsy

Arm Description

Blood samples for liquid biopsy

Outcomes

Primary Outcome Measures

To assess the efficacy of SBRT in inducing a regressive genetic trajectory of KRAS gene (evaluated by NGS technique) after SBRT treatment.

A genetic regressive trajectory is defined as KRAS mutated (any mutation) before SBRT and wild-type after SBRT (mutKRAS before SBRT→wtKRAS after SBRT). The sample size of the study is planned on this genetic trajectory, assuming a frequency of the phenomenon of 1/130 (as desumed from literature review). To be exhaustive, other realistic combinations are: wtKRAS→wtKRAS; mutKRAS→mutKRAS; wtKRAS→mutKRAS. Other assumptions for sample size calculation are: an alpha value of 0.05; a priori successful events rate of 0.077; 1-beta=0.60.

Secondary Outcome Measures

To evaluate the response according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, version 1.1 including any eventual abscopal effect.

To evaluate the responses' duration (measured from the time of documented objective response until documented tumor progression).

To evaluate the progression-free (PFS) survival (from the data of treatment start untill progression).

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.

The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline. Higher scores mean worse outcome.

Tumor immune microenvironment in primary tumour

Evaluate the tumor immune microenvironment (in particular the number of CD3+/CD8+/Granzyme B+ lymphocytes) of primary CRCs by immunohistochemistry (IHC).

Metabolic response (exploratory studies)

Assess the value of metabolic response by FDG-PET (fluorodeoxyglucose positron emission tomography) through SUV (Standardized Uptake Value) percentage modifications [(SUV after SBRT-SUV before SBRT/SUV before SBRT)x100].

Full Information

NCT ID

NCT04854213

First Posted

April 9, 2021

Last Updated

March 22, 2023

Sponsor

National Cancer Institute, Naples

1. Study Identification

Unique Protocol Identification Number

NCT04854213

Brief 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)

Acronym

PRELUDE-1

Official Title

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Recruiting

Study Start Date

October 6, 2021 (Actual)

Primary Completion Date

June 2023 (Anticipated)

Study Completion Date

March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute, Naples

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer Metastatic

Keywords

SBRT, liquid biopsy, metastatic disease, cancer genetics, NGS, omCRC

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Liquid biopsy

Arm Type

Other

Arm Description

Blood samples for liquid biopsy

Intervention Type

Device

Intervention Name(s)

Stereotactic Body Radiation Therapy (SBRT)

Intervention Description

Radiation treatment

Primary Outcome Measure Information:

Title

To assess the efficacy of SBRT in inducing a regressive genetic trajectory of KRAS gene (evaluated by NGS technique) after SBRT treatment.

Description

Time Frame

40 days after the end of RT

Secondary Outcome Measure Information:

Title

To evaluate the response according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, version 1.1 including any eventual abscopal effect.

Time Frame

Up to 24 months after the end of RT

Title

To evaluate the responses' duration (measured from the time of documented objective response until documented tumor progression).

Time Frame

Up to 24 months after the end of RT

Title

To evaluate the progression-free (PFS) survival (from the data of treatment start untill progression).

Time Frame

Up to 24 months after the end of RT

Title

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.

Description

The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline. Higher scores mean worse outcome.

Time Frame

Up to 24 months after the end of RT

Title

Tumor immune microenvironment in primary tumour

Description

Evaluate the tumor immune microenvironment (in particular the number of CD3+/CD8+/Granzyme B+ lymphocytes) of primary CRCs by immunohistochemistry (IHC).

Time Frame

40 days after the end of RT

Title

Metabolic response (exploratory studies)

Description

Time Frame

40 days after the end of RT

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Paolo Muto, MD

Phone

0815903398

Ext

+39

p.muto@istitutotumori.na.it

First Name & Middle Initial & Last Name or Official Title & Degree

Alessandro Ottaiano, MD

Phone

0815903510

Ext

+39

a.ottaiano@istitutotumori.na.it

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Paolo Muto, MD

Organizational Affiliation

National Cancer Institute of Naples

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Alessandro Ottaiano, MD

Organizational Affiliation

National Cancer Institute of Naples

Official's Role

Principal Investigator

Facility Information:

Facility Name

Istituto Nazionale Tumori - Fondazione G. Pascale

City

Napoli

ZIP/Postal Code

80131

Country

Italy

Individual Site Status

Recruiting

12. IPD Sharing Statement

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