Colorectal CancerPhase 2NCT04535024
The Combination of Immunotherapy and Stereotactic Ablative Radiotherapy in MSS Oligometastatic Colorectal Cancer
A Phase 2 study testing Stereotactic Ablative Radiotherapy (SABR) and Sintilimab in people with Colorectal Cancer, run by Fudan University at 1 site in China.
Trial summary
This is a prospective, single-center, single-arm phase II clinical trial. This study aims to evaluate the safety and tolerability of stereotactic ablative radiotherapy (SABR) in combination with Sintilimab, and to examine the impact of the combination therapy on tumor control, long-term survival and quality of life in… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Stereotactic Ablative Radiotherapy (SABR) and Sintilimab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 4 Mar 2021to Dec 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-70 years old, regardless of gender
- Fully informed and willing to provide written informed consent for the trial
- ECOG performance status 0-1
- Has an investigator determined life expectancy of at least 6 months
- Histologically confirmed colorectal adenocarcinoma, with MSS or pMMR status
- Has 2-5 measurable metastatic lesions detected on imaging, with none of them indicated for surgery; or the participant refuses to receive surgery. Biopsy of metastasis is preferred, but not required
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- Has undergone at least one dose of first-line systemic chemotherapy, except for any type of immunotherapy
- Multiple sites of lesions can be safely treated by SABR, and at least one lesion spared from irradiation, so as for assessment. The maximum diameter of each lesion for irradiation is no more than 5cm.
- Demonstrate adequate organ function
- 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
Who cannot join
- Pregnant or lactating women
- Serious medical comorbidities precluding radiotherapy
- Prior radiotherapy to a site requiring treatment
- Malignant pleural effusion
- Inability to treat all sites of active disease
- Has clinical or radiologic evidence of spinal cord compression or tumor within 3mm of spinal cord on MRI.
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- Dominant brain metastasis requiring surgical decompression
- Has prior treatment with cancer immunotherapy including, but not limited to immune checkpoint inhibitors.
- 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.
- Has a known history of active Bacillus Tuberculosis
- Has active autoimmune disease that has required systemic treatment in the past 2 years
- Hypersensitivity to PD-1 inhibitor or any of its excipients.
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Zhen Zhang, MD, PhD, 18801735029, zhen_zhang@fudan.edu.cn
About this study
Official title: Phase II Trial of Multisite Stereotactic Ablative Radiotherapy (SABR) Combined With Sintilimab for Microsatellite Stable (MSS) Oligometastatic Colorectal Cancer
This is a prospective, single-center, single-arm phase II clinical trial. This study aims to evaluate the safety and tolerability of stereotactic ablative radiotherapy (SABR) in combination with Sintilimab, and to examine the impact of the combination therapy on tumor control, long-term survival and quality of life in patients with microsatellite stable (MSS) oligometastatic colorectal cancer.
A total of 60 MSS oligometastatic colorectal cancer patients will be recruited and receive multisite SABR followed by immunotherapy of Sintilimab within one week from completion. Sintilimab will be given at a fixed dose of 200mg (100mg if weight < 50 kg) via intravenous infusion on the first day of each cycle, repeated every three weeks. The dosing will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal. The tumor regression, disease control, adverse events and long-term survival will be analyzed.
Read the detailed description
Immune-checkpoint inhibitor (ICI) has led to a paradigm shift in the treatment of patients with metastatic cancer, as proved by improved survival and durable responses in a group of these patients. However, the response rates to ICI when given alone are limited. In gastrointestinal cancer, patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors shown a response rate of approximately 40% to ICI, while patients with microsatellite stable (MSS) or mismatch repair-proficient (pMMR) tumors respond poorly to ICI. Such observations have spurred efforts to expand the benefit of immunotherapy, especially in these immune "non-sensitive" tumors, by combining ICI with treatments that induce T-cell associated immune response such stereotactic ablative radiotherapy (SABR).
High-dose ablative radiation was showed to facilitate immunotherapy through promote the activation of innate and adaptive immune responses against tumors in preclinical model and early phase clinical trials. However, a large portion of trials which were launched to test the efficacy of radiotherapy and immunotherapy produced suboptimal results. One important reason could be that majority of these trails were designed with single lesion irradiation, which is insufficient to unveil enough tumor antigens and/or to break the barrier of immunosuppressive tumor microenvironment (TME).
The investigators hypothesized that irradiation to multiple or all sites of diseases is more likely to produce an optimized regimen with ICI by broadly stimulate anti-tumor immunity and reduce tumor burden. Therefore, this study plans to administrate SABR to as many metastatic lesions as possible, in combination with ICI (Sintilimab) in patients with MSS oligometastatic colorectal cancers, to assess safety and tolerability of the regimen, and evaluate its early efficacy as well.
- Conditions
- Colorectal Cancer
- Being tested
- Stereotactic Ablative Radiotherapy (SABR), Sintilimab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Ablative Radiotherapy (SABR)Radiation
We plan 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).
Treatment schedule is once per day and five days per week. Sequence of irradiation for multiple metastases is at the discretion of the investigators based on their experience.
SintilimabDrug
Starts within one week upon SABR completion: 200mg, d1, q3w; Continued until disease progression, unacceptable toxicity or patient withdrawal.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | A total of 60 MSS oligometastatic colorectal cancer patients will receive multisite SABR followed by Sintilimab within one week from completion.
The dosing will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal. Receives: Radiation: Stereotactic Ablative Radiotherapy (SABR); Drug: Sintilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
The percentage of patients with objective response in the non-irradiated metastatic lesions. Objective response is defined as complete response (CR) or partial response (PR) per response evaluation criteria (RECIST v1.1) and the immune related response criteria (iRECIST) after treatment.
Measured: Up to 2 years
Secondary outcomes (5)
Disease Control Rate
The percentage of patients with disease control in the non-irradiated metastatic lesions. Disease control is defined as CR, PR, or stable disease (SD) per RECIST v1.1 and iRECIST after treatment.
Measured: Up to 2 years
Duration of Response
Defined as the time between PR/CR and subsequent progression disease (PD) per RECIST v1.1 and iRECIST or death from any cause.
Measured: Up to 2 years
Progression-Free Survival
Defined as the time from initiation of treatment to PD or death from any cause.
Measured: Up to 3 years
Overall Survival
Defined as the time from initiation of treatment to death from any cause.
Measured: Up to 3 years
Acute Toxicity
The percentage of patients with treatment-related acute toxicities as assessed by NCI CTCAE v5.0, from treatment initiation until 90 days upon completion of immunotherapy.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2020
- Study start4 Mar 2021
- Primary completionJun 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhen Zhang, Fudan University
- Investigators
- Zhen Zhang, MD, PhD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04535024
- Sponsor's protocol ID
- FDRT-2019-251-1881
- Status last verified
- May 2021
- First submitted
- 27 Aug 2020
- Last updated
- 11 May 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Multisite Stereotactic Ablative Radiotherapy (SABR) Combined With Sintilimab for Microsatellite Stable (MSS) Oligometastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT04535024
- Acronym / sponsor ID
- FDRT-2019-251-1881
- Conditions
- Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 4 Mar 2021 (actual)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 1 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, single-center, single-arm phase II clinical trial. This study aims to evaluate the safety and tolerability of stereotactic ablative radiotherapy (SABR) in combination with Sintilimab, and to examine the impact of the combination therapy on tumor control, long-term survival and quality of life in patients with microsatellite stable (MSS) oligometastatic colorectal cancer.
A total of 60 MSS oligometastatic colorectal cancer patients will be recruited and receive multisite SABR followed by immunotherapy of Sintilimab within one week from completion. Sintilimab will be given at a fixed dose of 200mg (100mg if weight < 50 kg) via intravenous infusion on the first day of each cycle, repeated every three weeks. The dosing will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal. The tumor regression, disease control, adverse events and long-term survival will be analyzed.
Detailed description
Immune-checkpoint inhibitor (ICI) has led to a paradigm shift in the treatment of patients with metastatic cancer, as proved by improved survival and durable responses in a group of these patients. However, the response rates to ICI when given alone are limited. In gastrointestinal cancer, patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors shown a response rate of approximately 40% to ICI, while patients with microsatellite stable (MSS) or mismatch repair-proficient (pMMR) tumors respond poorly to ICI. Such observations have spurred efforts to expand the benefit of immunotherapy, especially in these immune "non-sensitive" tumors, by combining ICI with treatments that induce T-cell associated immune response such stereotactic ablative radiotherapy (SABR).
High-dose ablative radiation was showed to facilitate immunotherapy through promote the activation of innate and adaptive immune responses against tumors in preclinical model and early phase clinical trials. However, a large portion of trials which were launched to test the efficacy of radiotherapy and immunotherapy produced suboptimal results. One important reason could be that majority of these trails were designed with single lesion irradiation, which is insufficient to unveil enough tumor antigens and/or to break the barrier of immunosuppressive tumor microenvironment (TME).
The investigators hypothesized that irradiation to multiple or all sites of diseases is more likely to produce an optimized regimen with ICI by broadly stimulate anti-tumor immunity and reduce tumor burden. Therefore, this study plans to administrate SABR to as many metastatic lesions as possible, in combination with ICI (Sintilimab) in patients with MSS oligometastatic colorectal cancers, to assess safety and tolerability of the regimen, and evaluate its early efficacy as well.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Radiation: Stereotactic Ablative Radiotherapy (SABR), Drug: SintilimabA total of 60 MSS oligometastatic colorectal cancer patients will receive multisite SABR followed by Sintilimab within one week from completion. The dosing will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Aged 18-70 years old, regardless of gender
- Fully informed and willing to provide written informed consent for the trial
- ECOG performance status 0-1
- Has an investigator determined life expectancy of at least 6 months
- Histologically confirmed colorectal adenocarcinoma, with MSS or pMMR status
Key exclusion criteria (13 listed)
- Pregnant or lactating women
- Serious medical comorbidities precluding radiotherapy
- Prior radiotherapy to a site requiring treatment
- Malignant pleural effusion
- Inability to treat all sites of active disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic Ablative Radiotherapy (SABR)We plan 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). Treatment schedule is once per day and five days per week. Sequence of irradiation for multiple metastases is at the discretion of the investigators based on their experience. | Radiation | Treatment Arm |
| SintilimabStarts within one week upon SABR completion: 200mg, d1, q3w; Continued until disease progression, unacceptable toxicity or patient withdrawal. | Drug | Treatment Arm |
Primary outcome
Objective Response Rate
Time frame: Up to 2 years
The percentage of patients with objective response in the non-irradiated metastatic lesions. Objective response is defined as complete response (CR) or partial response (PR) per response evaluation criteria (RECIST v1.1) and the immune related response criteria (iRECIST) after treatment.
5 secondary outcomes
Disease Control Rate
Time frame: Up to 2 years
Duration of Response
Time frame: Up to 2 years
Progression-Free Survival
Time frame: Up to 3 years
Overall Survival
Time frame: Up to 3 years
Acute Toxicity
Time frame: Up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhen Zhang, MD, PhD principal investigator
Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stereotactic Ablative Radiotherapy (SABR) and Sintilimab in people with Colorectal Cancer, run by Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zhen Zhang, MD, PhD (18801735029, zhen_zhang@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2021.