The Combination of Immunotherapy and Stereotactic Ablative Radiotherapy in Oligometastatic Gastrointestinal Cancer

November 6, 2020 updated by: Zhen Zhang, Fudan University

Phase I Clinical Trial of Multisite Stereotactic Ablative Radiotherapy (SABR) Combined With Camrelizumab in Patients With Oligometastatic Gastrointestinal Cancer

This is a single-center, open-label, single-arm phase I clinical study to exploratory observe and evaluate the efficacy and safety of anti-PD-1 antibody (Camrelizumab for Injection) combined with multisite stereotactic ablative radiotherapy (SABR) in patients with oligometastatic gastrointestinal cancer.

According to the origin site of metastases, this study will consist of three subgroups, including gastric carcinoma group, colorectal carcinoma group and hepatocellular carcinoma group. For each of the subgroup, seven eligible patients with oligometastatic cancer originating from stomach, colon and liver, respectively will be recruited. All patients will receive multisite SABR followed by immunotherapy of Camrelizumab within one week from completion. Camrelizumab will be administered at a fixed dose of 200 mg intravenously (iv) on D1 in a 14-day cycle. The treatment will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal.

Tumor tissue samples, sections, paraffin blocks or biopsy blocks, and biomarkers, including but not limited to PD-L1 expression level and the proportion of positive cells, TMB level and MMR status, will be collected from subjects.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Fudan University Shanghai Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Aged 18-70 years old, regardless of gender;
  2. Fully informed and willing to provide written informed consent for the trial;
  3. ECOG performance status 0-1;
  4. Expected survival time ≥ 6 months;
  5. Has gastric carcinoma /colorectal carcinoma / hepatocellular carcinoma, confirmed by histopathology (or pathology consultation in our hospital) and measurable oligometastatic lesions on imaging (RECIST version 1.1); pathological diagnosis confirmation of oligometastatic lesions using biopsy tissue samples (e.g. obtained by hollow core needle, biopsy, excision, etc.) is recommended but not required;
  6. Has undergone curative treatment on the primary lesion at least three months ago, without local progression;
  7. Has received standard treatment prior to enrolment, except for any type of immunotherapy;
  8. Has no more than three metastatic lesions detected on imaging in single organ (e.g. lung, liver, brain, bone, etc.), and the total number of metastases is no more than five;
  9. Multiple sites of lesions can be safely treated by SABR; and the maximum diameter of each lesion for irradiation is no more than 5cm.
  10. Contraindicated for surgery or the participant refuses to receive surgery.
  11. Has adequate organ function to tolerate the regimen:
  12. Bone marrow function: neutrophils ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 90 g/L;
  13. Liver and kidney function: serum creatinine ≤ 1.5 times the upper limit of normal; AST and ALT ≤ 2.5 times the upper limit of normal or the presence of liver metastasis ≤ 5 times the upper limit of normal; total bilirubin ≤ 1.5 times the upper limit of normal, or patients with Gilbert's syndrome ≤ 2.5 times the upper limit of normal;
  14. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
  15. Non-lactating patients.

Exclusion Criteria:

  1. Pregnant or lactating women
  2. Serious medical comorbidities precluding radiotherapy
  3. Prior radiotherapy to a site requiring treatment
  4. Malignant pleural effusion
  5. Inability to treat all sites of active disease
  6. Has clinical or radiologic evidence of spinal cord compression or tumor within 3mm of spinal cord on MRI.
  7. Dominant brain metastasis requiring surgical decompression
  8. Has prior treatment with cancer immunotherapy including, but not limited to immune checkpoint inhibitors.
  9. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose of >10 mg Prednisone daily or equivalent at time of trial treatment.
  10. Has a known history of active Bacillus Tuberculosis
  11. Has active autoimmune disease that has required systemic treatment in the past 2 years
  12. Hypersensitivity to PD-1 inhibitor or any of its excipients.
  13. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered from adverse events due to a previously administered agent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment Arm
Patients with oligometastatic gastrointestinal cancer will receive multisite SABR, followed by Camrelizumab within one week from completion of radiation. Camrelizumab for injection at 200 mg, d1, q2w, 14-day cycle will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal.
Radiation: Stereotactic Ablative Radiotherapy (SABR)
To irradiate as many metastatic lesions as possible, in the precondition that normal tissues can tolerate. Target dose will be adjusted depending on site of the lesion and organs at risk (BED > 100Gy). Sequence of irradiation for multiple metastases will be at the discretion of the investigators based on their experience.
Drug: Camrelizumab for injection (200 mg, iv), D1, Q2W, 14-day cycle
Administration of Carrelizumab will be started within one week upon SABR completion, and will be continued for up to two years until disease progression, unacceptable toxicity or patient withdrawal.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose-limiting toxicities (DLT)
Time Frame: Up to 2 years
Defined as treatment-related Grade 3 or higher toxicities (excluding asymptomatic biochemical abnormalities) within 3 months, starting from the first day of radiotherapy. Toxicities will be assessed and graded according to NCI-CTCAE v5.0.
Up to 2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adverse events (AEs)
Time Frame: Up to 2 years
Assessed according to NCI-CTCAE v5.0., and summarized by type and severity in tabular format to examine their frequency, organ systems affected, severity, and relationship to study treatment.
Up to 2 years
Local control (LC)
Time Frame: Up to 2 years
Defined as stable disease, partial response, or complete response based on serial imaging with CT scan. Recurrence will be defined as a suspicious mass at the site of SABR treated lesion, progressing in size on 2 consecutive computed tomography scans at a minimum interval of 1 month, combined with a positive FDG-PET defined by a SUV max ≥ 5, or a biopsy-proven confirmation.
Up to 2 years
Progression-free survival (PFS)
Time Frame: Up to 2 years
Regional or distant disease progression according to RECIST v1.1 or death due to any cause
Up to 2 years
Overall survival (OS)
Time Frame: Up to 2 years
A subject will be classified as either alive or dead due to any cause. The time to event will be calculated as the time from Day 1 until date of death. Day 1 is the date of 1st treatment with SABR.
Up to 2 years
Quality of life assessment
Time Frame: Up to 2 years
Assessed with the Functional Assessment of Cancer Therapy: General (FACT-G)
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 6, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 12, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 12, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MA-CRC-I-002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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