Advanced Rectal CancerPhase 2Miracle-2NCT05359406
A Combination Therapy Including Anti-PD-1 Immunotherapy in Rectal Cancer With Refractory Distal Metastasis
A Phase 2 study testing a combination therapy including tislelizumab in people with Advanced Rectal Cancer and Distal Metastasis, run by LI XIN-XIANG at 1 site in China.
Trial summary
Though surgical resection remains the primary choice for advanced rectal cancer, about 80% are considered unresectable due to the number, size, or location of metastases. The overall prognosis of patients who accepted traditional treatment methods is still poor. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Advanced Rectal Cancer, Distal Metastasis
- What is being tested?
- a combination therapy including tislelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2022to 1 Dec 2024
- 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
- Age 18~70;
- Patient signs informed consent;
- ECOG score 0~1;
- Initial colonoscopy and pathology: adenocarcinoma;
- MRI: rectal cancer located less than 10cm from the anus;
- Imaging confirms multiple measurable metastases exist in the liver or lung , which are evaluated as NED unacceptable by MDT discussion;
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- no previous treatment;
- Patients have adequate organ function;
- No contraindications to surgery or chemoradiation;
- The relevant test results within 7 days before the first dose must meet the following requirements:
- Blood routine examination (no blood transfusion within 7 days before screening, no correction with hematopoietic stimulating factor drugs):
- Hb≥90g/L
- ANC≥1.5×10^9/L; LC≥0.5×10^9/L;
- PLT≥100×10^9/L;
- WBC≥3.0×10^9/L, ≤15×10^9/L;
- Blood chemistry (no blood transfusion or albumin within 7 days prior to screening):
- ALT, AST≤1.5 ULN;
- ALP≤2.5 ULN;
- TBIL≤1.5 ULN;
- Cr≤1.5 ULN, CrCL≥50 mL/min;
- PT, APTT≤1.5 ULN, INR≤1.5 ULN(not receiving anticoagulation);
- TSH is within the normal range; if TSH is out of the normal range, FT3 and FT4 should be investigated. If the test results of FT3/FT4 cannot be obtained, T3 and T4 can be accepted. If the level of T3/T4 is normal, the patients can be selected.
- Urine test: urine protein<2+; if the urine protein≥2+, the 24-hour urine protein quantification must be≤1g;
- Echocardiography: LVEF≥55%;
- 12-lead ECG: Fridericia corrected QTcF<470 msec.
- Expected survival time >6 months;
- The gene status of KRAS, NRAS, BRAF and HER2 is clear;
- Patients are willing and able to follow the protocol during the study, including receiving treatment and scheduled follow-up and examination.
Who cannot join
- Patients will not be accepted into this study if they meet any of the following criteria:
- 1. History of tumor-related disease and treatment:
- Age <18 or >75 years;
- other malignancy within 5 years, except adequately treated carcinoma in situ of the cervix or squamous cell carcinoma of the skin, or largely controlled basal cell carcinoma of the skin;
- malignant pleural effusion or malignant ascites;
- patients with severe medical comorbidities that preclude radiotherapy and surgery;
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- previously treated;
- clinical or radiological evidence of spinal cord compression or a tumor within 3mm of the spinal cord on MRI
- the presence of distant metastases besides the liver and lungs, including brain, bone, ovarian, peritoneal and retroperitoneal multiple lymph node metastases;
- Patients who are considered suitable for using intense systemic treatment to achieve conversion after MDT discussion;
- pathological diagnosis of indolent cell carcinoma;
- patients with microsatellite instability or dMMR;
- patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc. that require emergency surgical resection;
- 2. Co-morbidities and treatment history:
- Presence of immunodeficiency disorders, including primary immunodeficiency disorders (e.g. caused by genetic factors) or secondary immunodeficiency disorders (e.g. caused by HIV infection or treatment related to immunological agents, etc.);
- Presence of any autoimmune disease that still requires treatment or a previous history of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, rheumatic heart valve disease, glomerulonephritis, etc. Excluding hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement therapy and type I diabetes with manageable and stable blood glucose;
- known or suspected interstitial pneumonia; other moderate to severe lung disease that may interfere with the detection or management of drug-related pulmonary toxicity and severely affect respiratory function, including idiopathic pulmonary tissue fibrosis, mechanized pneumonia/occlusive fine bronchitis, etc.;
- severe cardiovascular disease, including but not limited to conditions meeting NYHA criteria (Class III or higher), or myocardial infarction or cerebrovascular accident (cerebral ischaemia, symptomatic cerebral infarction, etc.) occurring within 3 months prior to the first dose, or unstable arrhythmia or unstable angina pectoris with coronary artery disease occurring within 1 month prior to the first dose, or congestive heart failure, or pre-existing symptomatic superior vena cava syndrome, etc.;
- an arteriovenous thrombotic event, such as deep vein thrombosis and pulmonary embolism, within the previous 3 months;
- history of live attenuated vaccination within 28 days prior to the first study dose or anticipated need for live attenuated vaccination during the study;
- active hepatitis B (defined as positive hepatitis B virus surface antigen [HBsAg] test result and HBV-DNA test value ≥ 500 IU/ml);
- Hepatitis C (defined as a positive test result for hepatitis C virus antibody [HCV-Ab]) ;
- history of tuberculosis infection or treatment within 1 year prior to signing informed consent;
- presence of severe infection within 4 weeks prior to first dose, including but not limited to bacteremia requiring hospitalization, severe pneumonia, etc.; or active infection requiring systemic antibiotic therapy according to NCI-CTCAE v5.0 grade ≥ 2 within 2 weeks prior to first dose, or unexplained fever >38.5°C during screening/prior to first dose (at the investigator's discretion, due to oncologic causes fever due to tumor causes may be enrolled);
- previous allogeneic bone marrow transplantation or solid organ transplantation received or intended to be received;
- Hemoptysis with a maximum daily hemoptysis of approximately ≥2.5 ml within 2 months prior to signing informed consent; clinically significant bleeding symptoms or a clear bleeding tendency within 1 month prior to signing informed consent, e.g. gastrointestinal bleeding, bleeding gastric ulcer, fecal occult blood ++ at baseline, vasculitis; known hereditary or acquired bleeding and thrombotic tendencies, e.g. hemophilia, impaired coagulation skills, thrombocytopenia, hypersplenism, etc.;
- abnormal coagulation (INR > 1.5 or APTT > 1.5 × ULN) with bleeding tendency or undergoing thrombolysis or requiring long-term anticoagulation with warfarin or heparin, or requiring long-term antiplatelet therapy (aspirin ≥ 300 mg/day or clopidogrel ≥ 75 mg/day)
- peripheral neuropathy ≥ grade 2 according to NCI-CTCAE v5.0;
- Co-morbidities of other infectious diseases that are not suitable for participation in this study.
Trial locations and contacts
1 site in 1 country.
China1 site
Xinxiang Li
Shanghai, Shanghai Municipality, 200032
Xinxiang Li, MD, +862164175590, lxx1449@163.com
About this study
Official title: Radiotherapy Followed by Chemotherapy With Target Therapy and Anti-PD-1 Immunotherapy in Locally Advanced Rectal Cancer With Refractory Liver Metastasis/Pulmonary Metastasis(Miracle-2): A Prospective, Single Arm, Multi-Center, Phase II Clinical Trial
Though surgical resection remains the primary choice for advanced rectal cancer, about 80% are considered unresectable due to the number, size, or location of metastases. The overall prognosis of patients who accepted traditional treatment methods is still poor. Therefore, the investigators designed a combination therapy, short-course radiotherapy followed by chemotherapy with target therapy and anti-PD-1 immunotherapy. This study implement the combination therapy in patients with rectal cancer who are initially unresectable in the locally advanced stage with multiple liver/pulmonary metastases, to evaluate whether they can improve the objective response rate, the conversion rate of radical surgery and prolong the overall survival of patients, and strive to provide high-level medical evidence for the clinical treatment.
- Conditions
- Advanced Rectal Cancer, Distal Metastasis
- Being tested
- a combination therapy including tislelizumab
- Keywords
- anti-PD-1 immunotherapy, short-course radiotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
a combination therapy including tislelizumabCombination product
Also called Radiotherapy Followed by Chemotherapy with target therapy and anti-PD-1 immunotherapy
For liver/pulmonary metastasis, the treatment plan is to implement large fraction radiotherapy for 4-8 times. For primary rectum lesion, short-course radiotherapy regimen through intensity-modulated radiotherapy will be applied with dose of 25Gy/5Fx. Immunotherapy contains anti-PD-1 monoclonal antibody, Tislelizumab(200mg, d1, q3w, i.v). For patients with RAS or BRAF mutation, chemotherapy adopts FOLFOX+BEV plan. For patients without RAS or BRAF mutation, chemotherapy adopts FOLFIRI+CET plan.
Patients will be followed for safety during the study. The safety follow-up period is defined as 90 days after the last dose of tislelizumab. Safety related data will be collected from the time of signing the informed consent until the end of the safety follow-up period or the start of new therapy.
| Study group | Role | What they receive |
|---|---|---|
| unresectable group | Experimental | Patients will receive tislelizumab in combination with radiotherapy and targeted therapy. 2 weeks after large fractionated radiotherapy for primary rectum lesion and metastasis, patients will be treated with systemic treatment including chemotherapy combined with targeted therapy and immunotherapy. Patients will be evaluated by MDT every 2 months since the beginning of the treatment. Those who are regarded as NED will be treated surgically/locally. Those in stable or partial remission will continue with combination therapy. Those with progressive disease will be withdrawn from study. Patients who are not surgically treatable will continue with combination therapy until disease progression or receiving surgical treatment. Receives: Combination Product: a combination therapy including tislelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early Tumor Shrinkage
The relative change of the sum of the longest diameters of the baseline RECIST target lesion at 8 weeks of systemic therapy, distinguished by 20% as the cut-off point between early response and no response.
Measured: 5 years after intervention
Secondary outcomes (5)
Disease Control Rate
Percentage of patients with disease control in non-irradiated metastatic lesions
Measured: 5 years after intervention
Duration of Response
The time between PR/CR and subsequent progressive disease or death of any cause.
Measured: 5 years after intervention
Overall Survival
The time from the beginning of treatment to the date of death.
Measured: 5 years after intervention
Progression-Free Survival
The time from the start of treatment to PD or death of any cause.
Measured: 5 years after intervention
Acute toxicity associated with immunotherapy
Proportion of patients with treatment-related acute toxicity.
Measured: from the beginning of the treatment to 90 days after the end of immunotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2022
- Study start1 Dec 2022 (estimated)
- Primary completion1 Jun 2024 (estimated)
- Study completion1 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Rectal CancerStudies of the same condition, open and under way.
- 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
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- LI XIN-XIANG
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, LI XIN-XIANG, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05359406
- Sponsor's protocol ID
- Miracle-2
- Acronym
- Miracle-2
- Status last verified
- Nov 2022
- First submitted
- 28 Apr 2022
- Last updated
- 15 Nov 2022
- 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 15 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiotherapy Followed by Chemotherapy With Target Therapy and Anti-PD-1 Immunotherapy in Locally Advanced Rectal Cancer With Refractory Liver Metastasis/Pulmonary Metastasis(Miracle-2): A Prospective, Single Arm, Multi-Center, Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT05359406
- Acronym / sponsor ID
- Miracle-2 / Miracle-2
- Conditions
- Advanced Rectal Cancer, Distal Metastasis
- Keywords
- anti-PD-1 immunotherapy, short-course radiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- LI XIN-XIANGUniversity, hospital or other
- Study start
- 1 Dec 2022 (estimated)
- Primary completion
- 1 Jun 2024 (estimated)
- Study completion
- 1 Dec 2024 (estimated)
- First posted
- 3 May 2022 (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.
Though surgical resection remains the primary choice for advanced rectal cancer, about 80% are considered unresectable due to the number, size, or location of metastases. The overall prognosis of patients who accepted traditional treatment methods is still poor. Therefore, the investigators designed a combination therapy, short-course radiotherapy followed by chemotherapy with target therapy and anti-PD-1 immunotherapy. This study implement the combination therapy in patients with rectal cancer who are initially unresectable in the locally advanced stage with multiple liver/pulmonary metastases, to evaluate whether they can improve the objective response rate, the conversion rate of radical surgery and prolong the overall survival of patients, and strive to provide high-level medical evidence for the clinical treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| unresectable group | Experimental | Combination Product: a combination therapy including tislelizumabPatients will receive tislelizumab in combination with radiotherapy and targeted therapy. 2 weeks after large fractionated radiotherapy for primary rectum lesion and metastasis, patients will be treated with systemic treatment including chemotherapy combined with targeted therapy and immunotherapy. Patients will be evaluated by MDT every 2 months since the beginning of the treatment. Those who are regarded as NED will be treated surgically/locally. Those in stable or partial remission will continue with combination therapy. Those with progressive disease will be withdrawn from study. Patients who are not surgically treatable will continue with combination therapy until disease progression or receiving surgical treatment. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Age 18~70;
- Patient signs informed consent;
- ECOG score 0~1;
- Initial colonoscopy and pathology: adenocarcinoma;
- MRI: rectal cancer located less than 10cm from the anus;
Key exclusion criteria (29 listed)
- Age <18 or >75 years;
- other malignancy within 5 years, except adequately treated carcinoma in situ of the cervix or squamous cell carcinoma of the skin, or largely controlled basal cell carcinoma of the skin;
- malignant pleural effusion or malignant ascites;
- patients with severe medical comorbidities that preclude radiotherapy and surgery;
- previously treated;
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 |
|---|---|---|
| a combination therapy including tislelizumabAlso: Radiotherapy Followed by Chemotherapy with target therapy and anti-PD-1 immunotherapyFor liver/pulmonary metastasis, the treatment plan is to implement large fraction radiotherapy for 4-8 times. For primary rectum lesion, short-course radiotherapy regimen through intensity-modulated radiotherapy will be applied with dose of 25Gy/5Fx. Immunotherapy contains anti-PD-1 monoclonal antibody, Tislelizumab(200mg, d1, q3w, i.v). For patients with RAS or BRAF mutation, chemotherapy adopts FOLFOX+BEV plan. For patients without RAS or BRAF mutation, chemotherapy adopts FOLFIRI+CET plan. Patients will be followed for safety during the study. The safety follow-up period is defined as 90 days after the last dose of tislelizumab. Safety related data will be collected from the time of signing the informed consent until the end of the safety follow-up period or the start of new therapy. | Combination product | unresectable group |
Primary outcome
Early Tumor Shrinkage
Time frame: 5 years after intervention
The relative change of the sum of the longest diameters of the baseline RECIST target lesion at 8 weeks of systemic therapy, distinguished by 20% as the cut-off point between early response and no response.
5 secondary outcomes
Disease Control Rate
Time frame: 5 years after intervention
Duration of Response
Time frame: 5 years after intervention
Overall Survival
Time frame: 5 years after intervention
Progression-Free Survival
Time frame: 5 years after intervention
Acute toxicity associated with immunotherapy
Time frame: from the beginning of the treatment to 90 days after the end of immunotherapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2022.
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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.
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 a combination therapy including tislelizumab in people with Advanced Rectal Cancer and Distal Metastasis, run by LI XIN-XIANG 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 28 inclusion and 29 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 15 Nov 2022. 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 Xinxiang Li, MD (+862164175590, lxx1449@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early Tumor Shrinkage (time frame: 5 years after intervention). 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 15 Nov 2022.