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Advanced Rectal CancerPhase 2Miracle-1NCT05359393

A Combination Therapy Including Anti-PD-1 Immunotherapy in MSS Rectal Cancer With Resectable Distal Metastasis

A Phase 2 study testing a combination therapy including tislelizumab in people with Advanced Rectal Cancer and Liver Metastasis, run by Fudan University at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

Although patients with locally advanced rectal cancer and resectable liver/pulmonary metastasis could benefit from surgery resection, these patients still have a poorer prognosis compared to those without distal metastasis. Read more about this study

Who is it for?
Ages 18 to 75 years
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
52 participants
Where
1 siteChina
Study dates
1 Dec 2022to 1 Sep 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18~75;
  • 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 that there are measurable metastases in the liver or lung, which are evaluated as NED acceptable 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 with microsatellite stability or mismatch repair protein defects;
  • 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. Contact the study team or a site near you to ask about taking part.

Xinxiang Li, MD contact

86-21-64175590

lxx1449@163.com

China1 site

  • Fudan University Shanghai Cancer Center

    Shanghai, Shanghai Municipality, 200032

Other trials in China

About this study

Official title: Radiotherapy Followed by Chemotherapy and Anti-PD-1 Immunotherapy in MSS Rectal Cancer With Resectable Liver/ Pulmonary Metastasis(Miracle-1): A Prospective, Single Arm, Multi-Center, Phase II Clinical Trial

Although patients with locally advanced rectal cancer and resectable liver/pulmonary metastasis could benefit from surgery resection, these patients still have a poorer prognosis compared to those without distal metastasis. Based on previous studies, there is no confirmation of whether these patients could benefit from preoperative immunotherapy combined with conventional chemoradiotherapy. This study proposes a combination therapy, preoperative short-course radiotherapy followed by neoadjuvant chemotherapy and anti-PD-1 immunotherapy, for microsatellite-stable patients with locally advanced rectal cancer and resectable liver/pulmonary metastasis, to assess its impact on tumor retreat, decline of postoperative metastasis and recurrence, and the disease-free survival and overall survival of patients. Besides, this study will provide high-level medical evidence for future clinical treatment of patients with advanced rectal cancer.

Being tested
a combination therapy including tislelizumab

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 preoperative radiotherapy combined with immunotherapy and chemotherapy

    Patients will receive tislelizumab in combination with neoadjuvant radiotherapy and chemotherapy, and will be evaluated 2-3 weeks after completion of the treatment. Those patients who achieve complete clinical regression of the lesion can choose observation, but for those without CCR, surgical resection (TME of the primary lesion, surgical resection of metastases or other destructive local treatment) will be applied. Patients will continue to receive tislelizumab for one year after surgery or during observation.

    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 x6, i.v). Chemotherapy adopts CAPEOX plan, including Capecitabine(1000mg/m2 bid, d1-14, p.o) and oxaliplatin(130mg/m2, d1, i.v).

Study groups in NCT05359393
Study groupRoleWhat they receive
resectable groupExperimentalIn this group, we propose a combination therapy, preoperative short-course radiotherapy followed by neoadjuvant chemotherapy and anti-PD-1 immunotherapy, for microsatellite-stable patients with locally advanced rectal cancer and resectable liver/pulmonary metastasis.
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.

  1. NED rate

    rate of no evidence of disease for one year

    Measured: 1 years after treatment

Secondary outcomes (6)

  1. Overall Survival

    For patients who still survive when the final analysis takes place, the date of the last 1 contact will be recorded.

    Measured: 5 years after surgery

  2. Disease Free Survival

    DFS refers to the period of time between the date of surgery and the day of the patient's tumor recurrence or death (earliest occurrence).

    Measured: 5 years after surgery

  3. Local Recurrence

    The date of recurrence is defined as the date on which an objective examination yields a positive result.

    Measured: 5 years after surgery

  4. Objective Response Rate

    Percentage of patients with objective response to primary or metastatic lesions

    Measured: 5 years after surgery

  5. Tumor Regression Rate

    Surgical excision specimens are taken every 1 cm, and the sections are given to at least 2 pathologists for independent scoring

    Measured: 5 years after surgery

  6. Acute toxicity associated with immunotherapy

    According to the NCI CTCAE v5.0 assessment, the proportion of patients with treatment-related acute toxicity developed from the beginning of treatment to 90 days after the end of immunotherapy

    Measured: from the beginning of 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.

  1. First posted3 May 2022
  2. Study start1 Dec 2022 (estimated)
  3. Primary completion1 Sep 2027 (estimated)
  4. Study completion1 Sep 2027 (estimated)

Resources

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
52 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05359393
Sponsor's protocol ID
Miracle-1
Acronym
Miracle-1
Status last verified
Nov 2022
First submitted
28 Apr 2022
Last updated
14 Nov 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

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 Liver Metastasis, 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 29 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: opening soon, as of the sponsor's last update on 14 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Xinxiang Li, MD (86-21-64175590, lxx1449@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

NED rate (time frame: 1 years after treatment). 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 NCT05359393.

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 14 Nov 2022.

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