Metastatic Colorectal CancerPhase 2NCT04948034
The Combination of Fruquintinib, Tislelizumab and Stereotactic Ablative Radiotherapy in Metastatic Colorectal Cancer(RIFLE)
A Phase 2 study testing Stereotactic Ablative Radiotherapy (SABR), Fruquintinib and Tislelizumab in people with Metastatic 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 Fruquintinib and Tislelizumab, and to examine the impact of the combination therapy on tumor control, long-term survival and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Stereotactic Ablative Radiotherapy (SABR), Fruquintinib and Tislelizumab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteChina
- Study dates
- 23 Aug 2021to 31 Dec 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged over 18 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 or cytologically confirmed stage IV colorectal cancer (UICC 8th version)
- Has at least 2 measurable oligometastatic lesions on imaging (RECIST version 1.1). One will be treated with SABR and the other will be biopsied and evaluated against RECIST 1.1.
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- Has progressive disease after receiving first-line standard antitumor therapy (chemotherapeutic agents including fluorouracil, oxaliplatin and irinotecan); previous neoadjuvant or adjuvant pelvic area radiotherapy is allowed; subjects included in the safety introduction phase may include third-line treatment or above, but these subjects will not be included in the final statistical analysis.
- Subjects receiving adjuvant oxaliplatin should progress during adjuvant therapy or within 6 months after completion.
- Demonstrate adequate organ function (bone marrow, liver, kidney and clotting function) within 7 days before the first administration without using blood products or hematopoietic stimulating factors.
- Subjects who withdraw from standard treatment before disease progressing due to unacceptable toxicity and exclude the use of the same drug are also allowed to be included.
- Non pregnant or lactating patients. Effective contraceptive methods should be used during the study and within 6 months of the last administration.
Who cannot join
- Pregnant or lactating women
- The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years excluding adequately treated non-melanoma skin cancer, carcinoma in situ of cervix and superficial bladder tumor (non-invasive tumor, or carcinoma in situ, or T1)
- Baseline laboratory indicators do not meet the following criteria: neutrophils ≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L , ALT ≤2.5 ULN, AST ≤2.5 ULN, Cr≤ 1.5 ULN or creatinine clearance rate <50ml/min, TBIL ≤1.5 ULN, APTT ≤1.5 ULN, PT ≤1.5 ULN (the criteria of patients with liver metastasis: PLT ≥80×10^9/L, ALT ≤5 ULN, AST ≤5 ULN, TBIL ≤2.5 ULN)
- Serious electrolyte abnormalities
- Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h
- Uncontrolled hypertension: SBP >140mmHg or DBP > 90mmHg
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- Receiving radiotherapy within 4 weeks
- Receiving anti-VEGF or anti-EGFR therapy within 4 weeks
- Stroke event or transient ischemic attack occurred within 12 months
- A history of arterial thrombosis or deep vein thrombosis within 6 months; a history of bleeding or evidence of bleeding tendency within 2 months
- A histroy of heart disease within 6 months (including congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting, cardiac insufficiency ≥ NYHA grade 2 and LVEF<50%)
- Uncontrolled malignant pleural effusion, ascites, or pericardial effusion
- Previous treatment with immunotherapy or fruquintinib
- The presence of gastrointestinal diseases such as gastric or duodenal active ulcers, ulcerative colitis or unresected tumors with active bleeding; or other conditions likely to cause gastrointestinal bleeding or perforation; or unhealed gastrointestinal perforation or gastrointestinal fistula after surgical treatment
- A history of liver disease including, but not limited to HBV infection or HBV DNA positive(≥1×10^4/ml), HCV infection or HCV DNA positive(≥1×10^3/ml) and liver cirrhosis
- Serious mental abnormalities
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: A Phase Ⅱ Trial of Multisite Stereotactic Ablative Radiotherapy (SABR) Combined With Fruquintinib and Tislelizumab in Metastatic 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 Fruquintinib and Tislelizumab, and to examine the impact of the combination therapy on tumor control, long-term survival and quality of life in patients with Metastatic colorectal cancer.
A total of 68 metastatic colorectal cancer patients who have failed the first-line standard treatment, will be recruited and receive multisite SABR(8-12 Gy, 4-5 times) followed by fruquintinib(5mg, qd) and tislelizumab(200mg, q3w) within two weeks from completion.The overall response rate (ORR), disease control rate(DCR), progression-free survival(PFS) and overall survival(OS) will be analyzed.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Stereotactic Ablative Radiotherapy (SABR), Fruquintinib, Tislelizumab
- 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.
FruquintinibDrug
Starts within two weeks upon SABR completion: 5mg, d1-14, qd; Continued until disease progression, unacceptable toxicity or patient withdrawal.
TislelizumabDrug
Starts within one week upon SABR completion: 200mg, d1, q3w; the dosing will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | A total of 68 metastatic colorectal cancer patients who have failed the first-line standard treatment will receive multisite SABR followed by Fruquintinib and Tislelizumab within two weeks from completion.
The dosing of Tislelizumab will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal. Receives: Radiation: Stereotactic Ablative Radiotherapy (SABR); Drug: Fruquintinib; Drug: Tislelizumab |
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 Jul 2021
- Study start23 Aug 2021
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic 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
- 68 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
- NCT04948034
- Sponsor's protocol ID
- FDRT-2020-274-2194
- Status last verified
- Jun 2021
- First submitted
- 23 Jun 2021
- Last updated
- 27 Aug 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Wang K, Chen Y, Zhang Z, Wu R, Zhou M, Yang W, Wan J, Shen L, Zhang H, Wang Y, Han X, Wang J, Zhang Z, Xia F. RIFLE: a Phase II trial of stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer. Gastroenterol Rep (Oxf). 2023 Oct 11;11:goad063. doi: 10.1093/gastro/goad063. eCollection 2023.
PubMed 37842200
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ⅱ Trial of Multisite Stereotactic Ablative Radiotherapy (SABR) Combined With Fruquintinib and Tislelizumab in Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT04948034
- Acronym / sponsor ID
- FDRT-2020-274-2194
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 23 Aug 2021 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 1 Jul 2021 (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 Fruquintinib and Tislelizumab, and to examine the impact of the combination therapy on tumor control, long-term survival and quality of life in patients with Metastatic colorectal cancer.
A total of 68 metastatic colorectal cancer patients who have failed the first-line standard treatment, will be recruited and receive multisite SABR(8-12 Gy, 4-5 times) followed by fruquintinib(5mg, qd) and tislelizumab(200mg, q3w) within two weeks from completion.The overall response rate (ORR), disease control rate(DCR), progression-free survival(PFS) and overall survival(OS) will be analyzed.
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: Fruquintinib, Drug: TislelizumabA total of 68 metastatic colorectal cancer patients who have failed the first-line standard treatment will receive multisite SABR followed by Fruquintinib and Tislelizumab within two weeks from completion. The dosing of Tislelizumab will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Aged over 18 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 or cytologically confirmed stage IV colorectal cancer (UICC 8th version)
Key exclusion criteria (16 listed)
- Pregnant or lactating women
- The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years excluding adequately treated non-melanoma skin cancer, carcinoma in situ of cervix and superficial bladder tumor (non-invasive tumor, or carcinoma in situ, or T1)
- Baseline laboratory indicators do not meet the following criteria: neutrophils ≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L , ALT ≤2.5 ULN, AST ≤2.5 ULN, Cr≤ 1.5 ULN or creatinine clearance rate <50ml/min, TBIL ≤1.5 ULN, APTT ≤1.5 ULN, PT ≤1.5 ULN (the criteria of patients with liver metastasis: PLT ≥80×10^9/L, ALT ≤5 ULN, AST ≤5 ULN, TBIL ≤2.5 ULN)
- Serious electrolyte abnormalities
- Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h
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 |
| FruquintinibStarts within two weeks upon SABR completion: 5mg, d1-14, qd; Continued until disease progression, unacceptable toxicity or patient withdrawal. | Drug | Treatment Arm |
| TislelizumabStarts within one week upon SABR completion: 200mg, d1, q3w; the dosing will continue for up to two years 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 27 Aug 2021.
- Derived from this study: PubMed 37842200Wang K, Chen Y, Zhang Z, Wu R, Zhou M, Yang W, Wan J, Shen L, Zhang H, Wang Y, Han X, Wang J, Zhang Z, Xia F. RIFLE: a Phase II trial of stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer. Gastroenterol Rep (Oxf). 2023 Oct 11;11:goad063. doi: 10.1093/gastro/goad063. eCollection 2023.
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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), Fruquintinib and Tislelizumab in people with Metastatic 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 11 inclusion and 16 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 27 Aug 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?
On the ClinicalTrials.gov record for NCT04948034, which also lists 1 linked publication.
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 27 Aug 2021.