CRCPhase 2NCT06593548
Lvosidenib (AK112) Combined With CapeOX and Radiotherapy in Patients With Unresectable Metastatic MSS-type Colorectal Cancer
A Phase 2 study testing Ivosidenib (AK112) in people with CRC and MSS, run by Fudan University at 1 site in China.
Trial summary
This is a prospective, single-arm, single-center Phase II clinical study. In this study, participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- CRC, MSS, Metastatic Cancer
- What is being tested?
- Ivosidenib (AK112)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2024to 1 Nov 2026
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-75.
- ECOG performance status of 0-1.
- Initial diagnosis confirmed by colonoscopy and pathology as colorectal adenocarcinoma.
- Imaging confirmation of multiple measurable metastases, deemed unresectable initially after MDT discussion.
- No prior treatment or more than 1 year since completion of initial untreated/post-operative adjuvant chemotherapy, and no previous anti-tumor therapy thereafter.
- With good organ function, without contraindications for surgery or chemotherapy.
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- Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, and international normalized ratio (INR) ≤ 1.5 × ULN (if not receiving anticoagulant therapy).
- Urine protein < 2+; if urine protein ≥ 2+, 24-hour urine protein quantitative test must show ≤ 1g protein.
- Left ventricular ejection fraction (LVEF) ≥ 55%. 12-lead electrocardiogram: Fridericia-corrected QT interval (QTcF) < 470 msec.
- Expected survival > 6 months.
- Clear status of KRAS, NRAS, BRAF, and HER2 genes.
- Microsatellite stable or mismatch repair protein proficient patients.
Who cannot join
- Age <18 years or >75 years.
- History of any other malignancy within 5 years, except adequately treated cervical carcinoma in situ, squamous cell carcinoma of the skin, or basal cell carcinoma that has been effectively controlled.
- Malignant pleural or peritoneal effusion.
- Severe internal medical complications preventing chemotherapy or surgery.
- Clinical or radiological evidence of spinal cord compression, or tumor within 3 mm of the spinal cord on MRI.
- Imaging-confirmed brain, ovarian, or peritoneal metastases.
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- Patients deemed suitable for aggressive systemic treatment to achieve conversion after MDT discussion.
- Pathologically diagnosed signet ring cell carcinoma.
- Patients with microsatellite instability or mismatch repair protein deficiencies.
- Patients with intestinal obstruction, perforation, bleeding requiring emergency surgical resection.
- Immunodeficiency diseases, including primary immunodeficiency diseases (genetically determined) or secondary immunodeficiency diseases.
- Known or suspected interstitial pneumonia.
- Severe cardiovascular diseases, including but not limited to conditions meeting NYHA class (III or higher), myocardial infarction or cerebrovascular accident (ischemic stroke, symptomatic cerebral infarction) within the past 3 months prior to first dosing, unstable angina or unstable arrhythmias within the past 1 month prior to first dosing, congestive heart failure beyond the above criteria, symptomatic superior vena cava syndrome, etc.
- Venous thromboembolic events within the past 3 months, such as deep vein thrombosis and pulmonary embolism.
- History of receiving live attenuated vaccines within 28 days prior to first study drug administration or anticipated need for live attenuated vaccines during the study period.
- Active hepatitis B (defined as positive hepatitis B surface antigen [HBsAg] with HBV-DNA ≥500 IU/ml).
- Hepatitis C (defined as positive hepatitis C virus antibody [HCV-Ab]).
- History of tuberculosis infection or treatment within the past 1 year prior to signing informed consent.
- History of or planned allogeneic bone marrow or solid organ transplantation.
- Abnormal coagulation function (INR > 1.5 or APTT > 1.5 × ULN), with bleeding tendency or undergoing thrombolysis or requiring long-term anticoagulant therapy with warfarin or heparin, or requiring long-term antiplatelet therapy (aspirin ≥ 300 mg/day or clopidogrel ≥ 75 mg/day).
- Peripheral neuropathy of Grade ≥2 according to NCI-CTCAE v5.0.
- Concurrent other infectious diseases unsuitable for participation in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Single-arm, Single-center, Phase II Clinical Study of Ivosidenib (AK112) Combined With CapeOX and Radiotherapy in Patients With Unresectable Metastatic MSS-type Colorectal Cancer: Efficacy and Safety Assessment
This is a prospective, single-arm, single-center Phase II clinical study. In this study, participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. The treatment regimen is as follows: participants will first receive Ivosidenib in combination with CapeOX chemotherapy during the first cycle, followed by radiotherapy starting 2 weeks after medication. Depending on the dose limits of normal tissue radiation, Stereotactic Ablative Radiotherapy (SABR), large fraction radiotherapy, or high-dose combined with low-dose radiotherapy will be administered to primary and metastatic lesions. One week after completing radiotherapy, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment. If extensive primary and metastatic lesions cannot be treated with radiotherapy initially, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment until the lesions shrink, at which point radiotherapy may be considered.
Assessments will be conducted every 2 treatment cycles after treatment initiation, with multidisciplinary team (MDT) discussions to determine if No Evidence of Disease (NED) is achieved. Patients achieving NED may undergo surgery or local treatment, while those with stable or partial responses will continue combination therapy. Patients with disease progression will discontinue study treatment. Patients ineligible for surgical treatment will continue combination therapy until disease progression or until they exit the study for surgical treatment.
During the study period, participants will undergo safety monitoring. The safety follow-up period is defined as 90 days after the last dose of Ivosidenib. Safety data will be collected from the time of informed consent signing until the end of the safety follow-up period or initiation of new anti-tumor treatment (whichever occurs first).
Read the detailed description
This is a prospective, single-arm, single-center Phase II clinical study. In this study, participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. The treatment regimen is as follows: participants will first receive Ivosidenib in combination with CapeOX chemotherapy during the first cycle, followed by radiotherapy starting 2 weeks after medication. Depending on the dose limits of normal tissue radiation, Stereotactic Ablative Radiotherapy (SABR), large fraction radiotherapy, or high-dose combined with low-dose radiotherapy will be administered to primary and metastatic lesions. One week after completing radiotherapy, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment. If extensive primary and metastatic lesions cannot be treated with radiotherapy initially, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment until the lesions shrink, at which point radiotherapy may be considered.
Assessments will be conducted every 2 treatment cycles after treatment initiation, with multidisciplinary team (MDT) discussions to determine if No Evidence of Disease (NED) is achieved. Patients achieving NED may undergo surgery or local treatment, while those with stable or partial responses will continue combination therapy. Patients with disease progression will discontinue study treatment. Patients ineligible for surgical treatment will continue combination therapy until disease progression or until they exit the study for surgical treatment.
During the study period, participants will undergo safety monitoring. The safety follow-up period is defined as 90 days after the last dose of Ivosidenib. Safety data will be collected from the time of informed consent signing until the end of the safety follow-up period or initiation of new anti-tumor treatment (whichever occurs first).
- Conditions
- CRC, MSS, Metastatic Cancer
- Being tested
- Ivosidenib (AK112)
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivosidenib (AK112)Drug
Participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. Participants will first receive Ivosidenib in combination with CapeOX during the first cycle, followed by radiotherapy starting 2 weeks after medication. Depending on the dose limits of normal tissue radiation, Stereotactic Ablative Radiotherapy (SABR), large fraction radiotherapy, or high-dose combined with low-dose radiotherapy will be administered to primary and metastatic lesions. One week after completing radiotherapy, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment. If primary and metastatic lesions are too extensive for initial radiotherapy, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment until the lesions shrink, at which point radiotherapy may be considered.。
| Study group | Role | What they receive |
|---|---|---|
| AK112 combined with CapeOX and radiotherapy | Experimental | Participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. Participants will first receive Ivosidenib in combination with CapeOX during the first cycle, followed by radiotherapy starting 2 weeks after medication. Receives: Drug: Ivosidenib (AK112) |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
Progression-Free Survival (PFS)
Measured: The time from the start of treatment until disease progression (PD) or death from any cause，whichever came first, assessed up to 100 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start1 Nov 2024 (estimated)
- Primary completion1 Nov 2026 (estimated)
- Study completion1 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CRCStudies 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
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, LI XIN-XIANG, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06593548
- Sponsor's protocol ID
- Miracle-03
- Status last verified
- Sep 2024
- First submitted
- 6 Sep 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Single-arm, Single-center, Phase II Clinical Study of Ivosidenib (AK112) Combined With CapeOX and Radiotherapy in Patients With Unresectable Metastatic MSS-type Colorectal Cancer: Efficacy and Safety Assessment
- ClinicalTrials.gov ID
- NCT06593548
- Acronym / sponsor ID
- Miracle-03
- Conditions
- CRC, MSS, Metastatic Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 1 Nov 2024 (estimated)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 1 Nov 2026 (estimated)
- First posted
- 19 Sep 2024 (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-arm, single-center Phase II clinical study. In this study, participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. The treatment regimen is as follows: participants will first receive Ivosidenib in combination with CapeOX chemotherapy during the first cycle, followed by radiotherapy starting 2 weeks after medication. Depending on the dose limits of normal tissue radiation, Stereotactic Ablative Radiotherapy (SABR), large fraction radiotherapy, or high-dose combined with low-dose radiotherapy will be administered to primary and metastatic lesions. One week after completing radiotherapy, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment. If extensive primary and metastatic lesions cannot be treated with radiotherapy initially, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment until the lesions shrink, at which point radiotherapy may be considered.
Assessments will be conducted every 2 treatment cycles after treatment initiation, with multidisciplinary team (MDT) discussions to determine if No Evidence of Disease (NED) is achieved. Patients achieving NED may undergo surgery or local treatment, while those with stable or partial responses will continue combination therapy. Patients with disease progression will discontinue study treatment. Patients ineligible for surgical treatment will continue combination therapy until disease progression or until they exit the study for surgical treatment.
During the study period, participants will undergo safety monitoring. The safety follow-up period is defined as 90 days after the last dose of Ivosidenib. Safety data will be collected from the time of informed consent signing until the end of the safety follow-up period or initiation of new anti-tumor treatment (whichever occurs first).
Detailed description
This is a prospective, single-arm, single-center Phase II clinical study. In this study, participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. The treatment regimen is as follows: participants will first receive Ivosidenib in combination with CapeOX chemotherapy during the first cycle, followed by radiotherapy starting 2 weeks after medication. Depending on the dose limits of normal tissue radiation, Stereotactic Ablative Radiotherapy (SABR), large fraction radiotherapy, or high-dose combined with low-dose radiotherapy will be administered to primary and metastatic lesions. One week after completing radiotherapy, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment. If extensive primary and metastatic lesions cannot be treated with radiotherapy initially, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment until the lesions shrink, at which point radiotherapy may be considered.
Assessments will be conducted every 2 treatment cycles after treatment initiation, with multidisciplinary team (MDT) discussions to determine if No Evidence of Disease (NED) is achieved. Patients achieving NED may undergo surgery or local treatment, while those with stable or partial responses will continue combination therapy. Patients with disease progression will discontinue study treatment. Patients ineligible for surgical treatment will continue combination therapy until disease progression or until they exit the study for surgical treatment.
During the study period, participants will undergo safety monitoring. The safety follow-up period is defined as 90 days after the last dose of Ivosidenib. Safety data will be collected from the time of informed consent signing until the end of the safety follow-up period or initiation of new anti-tumor treatment (whichever occurs first).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AK112 combined with CapeOX and radiotherapy | Experimental | Drug: Ivosidenib (AK112)Participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. Participants will first receive Ivosidenib in combination with CapeOX during the first cycle, followed by radiotherapy starting 2 weeks after medication. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Aged 18-75.
- ECOG performance status of 0-1.
- Initial diagnosis confirmed by colonoscopy and pathology as colorectal adenocarcinoma.
- Imaging confirmation of multiple measurable metastases, deemed unresectable initially after MDT discussion.
- No prior treatment or more than 1 year since completion of initial untreated/post-operative adjuvant chemotherapy, and no previous anti-tumor therapy thereafter.
Key exclusion criteria (22 listed)
- Age <18 years or >75 years.
- History of any other malignancy within 5 years, except adequately treated cervical carcinoma in situ, squamous cell carcinoma of the skin, or basal cell carcinoma that has been effectively controlled.
- Malignant pleural or peritoneal effusion.
- Severe internal medical complications preventing chemotherapy or surgery.
- Clinical or radiological evidence of spinal cord compression, or tumor within 3 mm of the spinal cord on MRI.
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 |
|---|---|---|
| Ivosidenib (AK112)Participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. Participants will first receive Ivosidenib in combination with CapeOX during the first cycle, followed by radiotherapy starting 2 weeks after medication. Depending on the dose limits of normal tissue radiation, Stereotactic Ablative Radiotherapy (SABR), large fraction radiotherapy, or high-dose combined with low-dose radiotherapy will be administered to primary and metastatic lesions. One week after completing radiotherapy, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment. If primary and metastatic lesions are too extensive for initial radiotherapy, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment until the lesions shrink, at which point radiotherapy may be considered.。 | Drug | AK112 combined with CapeOX and radiotherapy |
Primary outcome
PFS
Time frame: The time from the start of treatment until disease progression (PD) or death from any cause，whichever came first, assessed up to 100 months
Progression-Free Survival (PFS)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Ivosidenib (AK112) in people with CRC and MSS, 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 12 inclusion and 22 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 19 Sep 2024. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: The time from the start of treatment until disease progression (PD) or death from any cause，whichever came first, assessed up to 100 months). 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 19 Sep 2024.