Rectal CancerPhase 3NeoCaCRT-IIINCT06832917
Short-course Radiation (SCRT) Followed by 6 Cycles of Cadonilimab Plus MFOLFOX6 As Neoadjuvant Therapy for Patients with Locally Advanced Rectal Cancer (LARC): a Multicenter, Two-arm Parallel, Open-label, Randomised Phase III Trial (NeoCaCRT-III)
A Phase 3 study testing AK104 plus and Chemo only in people with Rectal Cancer, run by Wan He.
Trial summary
The goal of this clinical trial is to learn if neoadjuvant short-course radiation (SCRT) followed by 6 cycles of cadonilimab plus mFOLFOX6 works to treat patients with locally advanced rectal cancer (LARC). It will also learn about the safety of the combined regimen. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- AK104 plus and Chemo only
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 238 participants
- Where
- No sites listed yet
- Study dates
- 31 Mar 2025to 31 Dec 2029
- Phase
- Phase 3
- 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 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Age ≥18 yeas and ≤79 years. The gender is not limited. 2. Histopathology confirmed the diagnosis of rectal adenocarcinoma. 3. Patients with rectal cancer based on endoscopic ultrasound and / or pelvic MRI contrast + contrast, chest CT, head MRI or CT + contrast, or PET / CT, staging criteria per AJCC 8th edition cancer stage, cT 3-T4 / N + M0.
- 4. At least 20 unstained sections of formalin-fixed paraffin-embedded tumor tissue sections, or fresh tumor tissue, can be provided for genomic and proteomic testing.
- 5. The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0- 1. 6. Adequate bone marrow and organ function meets the following criteria:
- Neutrophil count (ANC)≥1.5×l09/L
- Platelet (PLT) ≥80×109/L
- Hemoglobin (Hb) level ≥90 g/L
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- Total bilirubin level≤1.5×ULN
- Alanine aminotransferase (ALT) level≤3×ULN
- Aspartate aminotransferase (AST) level ≤3×ULN
- International normalized value (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5×ULN
- Serum creatinine (Cr) level ≤1.5×ULN
- Creatinine clearance #50 ml/min (Calculated according to the Cockcroft-Gault formula)
Who cannot join
- 1. Previous history of severe hypersensitivity to other monoclonal antibodies or any component of AK 104.
- 2. Preoperative pathology was diagnosed as squamous cell carcinoma or neuroendocrine tumor 3. Within 5 years before enrollment for malignancies other than colorectal cancer with negligible risk of metastasis or death (e. g., expected 5-year OS> 90%) and expected radical results after treatment (e. g., adequately treated cervical carcinoma in situ, basal or squamous cell skin carcinoma, localized prostate carcinoma for curative intent, ductal carcinoma in situ surgically treated with curative intent).
- 4. Previous treatment against the PD-1 receptor or its ligand PD-L1 or the cytotoxic T lymphocyte-associated protein-4 (CTLA-4) receptor.
- 5. History of autoimmune diseases, including but not limited to myasthenia gravis, myoitis, autoimmune hepatitis, series, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis related to antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, vasculitis, or glomerulnephritis; patients with autoimmune-related hypothyroidism were eligible for stable-dose thyroid hormone replacement therapy; patients with type 1 diabetes under control after a stable insulin regimen were eligible to participate in this study; 6. Receiving systemic immune stimulation drugs (including but not limited to interferon or IL-2) within 4 weeks prior to enrollment or within 5 half-lives of the drug (whichever is shorter); 7. Received systemic corticosteroids (> 10 mg/d of prednisone equivalent) or other systemic immunosuppressive agents (including but not limited to prednisone, prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents [anti-TNF]) within 2 weeks prior to enrollment. Local, ocular, intra-articular, nasal, and inhaled corticosteroids are permittedt; 8. Patients requiring baseline and subsequent MRI tumor evaluation with previous allergic reactions to intravenous contrast agents may use preventive steroids.
- 9. Allowing the use of inhaled corticosteroids for chronic obstructive pulmonary disease, corticosteroid hydrochloride (e. g., flurohydrocortisone) in patients with orthostatic hypotension, and low-dose corticosteroid maintenance for adrenal cortical insufficiency.
- 10. Patients with previous allogeneic bone marrow transplantation or previous solid organ transplantation.
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- 11. Idiopathic pulmonary fibrosis, drug-induced pneumonia, mechanical pneumonia (i. e. bronchiolitis obliterans), history of idiopathic pneumonia or chest CT scan at screening showed evidence of active pneumonia.
- 12. Any live vaccine (e. g., vaccine against infectious diseases, such as influenza vaccine, varicella vaccine, etc.) within 4 weeks (28 days) before enrollment.13 Active infections, including tuberculosis (clinical diagnosis including clinical history, physical examination and imaging findings, and TB tests performed per local medical practice), hepatitis B {known HBV surface antigen (HBsAg) positive and HBVDNA 1000 cps / ml}, hepatitis C or human immunodeficiency virus (HIV antibody positive).
- 13. Patients with prior or cured HBV infection (defined as hepatitis B core antibody [anti-HBc] positive and HbsAg negative) were to be eligible to participate in the study only if HBVDNA was negative (HBVDNA˂ 1000 cps / ml).
- 14. Patients with positive hepatitis C (HCV) antibody are not eligible for the study only if polymerase chain reaction shows negative HCVRNA.
- 15. Clinically meaningful basic medicine, disease (e. g., dyspnea, pneumonia, pancreatitis, poorly controlled, poorly controlled diabetes, infection active or poorly controlled, or drug or alcohol abuse).
- 16. Presence of severe neurological or psychiatric disorders, including dementia and epileptic seizures.
- 17. He had an NCI-CTCAE grade 2 peripheral neuropathy. 18. Female patients during pregnancy or lactation. 19. Chronic bowel disease or short bowel syndrome. 20. Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. 21. Major cardiovascular diseases, such as New York Heart Association heart disease (grade II or higher), myocardial infarction within 3 months before randomization, unstable arrhythmia, or unstable angina pectoris.
- 22. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction <50% must have an optimized stable medical regimen as determined by the treating physician, consulting a cardiologist if required.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Prospective Multicenter, Two-arm Parallel, Open-label, Randomised Phase III Study to Explore the Efficacy and Safety of Cadonilimab Plus Chemotherapy After Short-course Radiotherapy in Locally Advanced Rectal Cancer
The goal of this clinical trial is to learn if neoadjuvant short-course radiation (SCRT) followed by 6 cycles of cadonilimab plus mFOLFOX6 works to treat patients with locally advanced rectal cancer (LARC). It will also learn about the safety of the combined regimen. The main questions it aims to answer are:
Does the neoadjuvant SCRT plus dual immunotherapy and chemotherapy can improve pathological complete response(pCR) rate? What medical problems do participants have when receiving chemotherapy plus cadonilimab compared to chemotherapy only?
Participants will:
Receiving cadonilimab plus mFOLFOX6 or mFOLFOX6 every 2 weeks for 3 months Visit the clinic once every 2 weeks for checkups and tests
- Conditions
- Rectal Cancer
- Being tested
- AK104 plus, Chemo only
- Keywords
- Mismatch repair-proficient (pMMR) or microsatellite stability(MSS), Locally advanced rectal cancer (LARC), Short course radiation (SCRT)
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AK104 plusDrug
SCRT followed by 6 cycles of cadonilimab (AK104) plus mFOLFOX6 as neoadjuvant therapy for patients
Chemo onlyDrug
Short-course radiation (SCRT) followed by 6 cycles of mFOLFOX6 as neoadjuvant therapy for patients
| Study group | Role | What they receive |
|---|---|---|
| AK104 plus | Experimental | SCRT followed by AK104 plus chemotherapy Receives: Drug: AK104 plus; Drug: Chemo only |
| Chemo only | Other | SCRT followed by chemotherapy Receives: Drug: Chemo only |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-year disease free survival (3-y DFS)
The survival rate of patients without disease recurrence or death due to the disease progression patients at 36 months.
Measured: 3-year
Secondary outcomes (5)
Pathological complete response rate
The proportion of patients with no tumor cells in the postoperative specimens
Measured: Up to 6 months
Overall Survival
Time from the date of randomization until the date of death from any cause.
Measured: Up to 5 years
Objective Response Rate
The rate of participants that achieve either a complete response (CR) or a partial response (PR).
Measured: Up to 6 months
Clinical complete response rate
The disappearance of all detectable clinical and imaging evidence of a tumor after treatment
Measured: Up to 36 months
Incidence of adverse events
Number of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), AE of special interest (AESI), serious adverse event (SAE) assessed by CTCAE v5.0.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2025
- Study start31 Mar 2025 (estimated)
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 238 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wan He
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Wan He, Shenzhen People's Hospital
- Investigators
- WA He, Doctor, Principal investigator, Shenzhen Peolple's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06832917
- Sponsor's protocol ID
- Shenzhen CRC-005
- Acronym
- NeoCaCRT-III
- Status last verified
- Mar 2025
- First submitted
- 13 Feb 2025
- Last updated
- 11 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Multicenter, Two-arm Parallel, Open-label, Randomised Phase III Study to Explore the Efficacy and Safety of Cadonilimab Plus Chemotherapy After Short-course Radiotherapy in Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT06832917
- Acronym / sponsor ID
- NeoCaCRT-III / Shenzhen CRC-005
- Conditions
- Rectal Cancer
- Keywords
- Mismatch repair-proficient (pMMR) or microsatellite stability(MSS), Locally advanced rectal cancer (LARC), Short course radiation (SCRT)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 238 participants (estimated)
- Lead sponsor
- Wan HeUniversity, hospital or other
- Study start
- 31 Mar 2025 (estimated)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 18 Feb 2025 (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.
The goal of this clinical trial is to learn if neoadjuvant short-course radiation (SCRT) followed by 6 cycles of cadonilimab plus mFOLFOX6 works to treat patients with locally advanced rectal cancer (LARC). It will also learn about the safety of the combined regimen. The main questions it aims to answer are:
Does the neoadjuvant SCRT plus dual immunotherapy and chemotherapy can improve pathological complete response(pCR) rate? What medical problems do participants have when receiving chemotherapy plus cadonilimab compared to chemotherapy only?
Participants will:
Receiving cadonilimab plus mFOLFOX6 or mFOLFOX6 every 2 weeks for 3 months Visit the clinic once every 2 weeks for checkups and tests
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AK104 plus | Experimental | Drug: AK104 plus, Drug: Chemo onlySCRT followed by AK104 plus chemotherapy |
| Chemo only | Other | Drug: Chemo onlySCRT followed by chemotherapy |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 1. Age ≥18 yeas and ≤79 years. The gender is not limited. 2. Histopathology confirmed the diagnosis of rectal adenocarcinoma. 3. Patients with rectal cancer based on endoscopic ultrasound and / or pelvic MRI contrast + contrast, chest CT, head MRI or CT + contrast, or PET / CT, staging criteria per AJCC 8th edition cancer stage, cT 3-T4 / N + M0.
- 4. At least 20 unstained sections of formalin-fixed paraffin-embedded tumor tissue sections, or fresh tumor tissue, can be provided for genomic and proteomic testing.
- 5. The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0- 1. 6. Adequate bone marrow and organ function meets the following criteria:
Key exclusion criteria (14 listed)
- 1. Previous history of severe hypersensitivity to other monoclonal antibodies or any component of AK 104.
- 2. Preoperative pathology was diagnosed as squamous cell carcinoma or neuroendocrine tumor 3. Within 5 years before enrollment for malignancies other than colorectal cancer with negligible risk of metastasis or death (e. g., expected 5-year OS> 90%) and expected radical results after treatment (e. g., adequately treated cervical carcinoma in situ, basal or squamous cell skin carcinoma, localized prostate carcinoma for curative intent, ductal carcinoma in situ surgically treated with curative intent).
- 4. Previous treatment against the PD-1 receptor or its ligand PD-L1 or the cytotoxic T lymphocyte-associated protein-4 (CTLA-4) receptor.
- 5. History of autoimmune diseases, including but not limited to myasthenia gravis, myoitis, autoimmune hepatitis, series, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis related to antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, vasculitis, or glomerulnephritis; patients with autoimmune-related hypothyroidism were eligible for stable-dose thyroid hormone replacement therapy; patients with type 1 diabetes under control after a stable insulin regimen were eligible to participate in this study; 6. Receiving systemic immune stimulation drugs (including but not limited to interferon or IL-2) within 4 weeks prior to enrollment or within 5 half-lives of the drug (whichever is shorter); 7. Received systemic corticosteroids (> 10 mg/d of prednisone equivalent) or other systemic immunosuppressive agents (including but not limited to prednisone, prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents [anti-TNF]) within 2 weeks prior to enrollment. Local, ocular, intra-articular, nasal, and inhaled corticosteroids are permittedt; 8. Patients requiring baseline and subsequent MRI tumor evaluation with previous allergic reactions to intravenous contrast agents may use preventive steroids.
- 9. Allowing the use of inhaled corticosteroids for chronic obstructive pulmonary disease, corticosteroid hydrochloride (e. g., flurohydrocortisone) in patients with orthostatic hypotension, and low-dose corticosteroid maintenance for adrenal cortical insufficiency.
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 |
|---|---|---|
| AK104 plusSCRT followed by 6 cycles of cadonilimab (AK104) plus mFOLFOX6 as neoadjuvant therapy for patients | Drug | AK104 plus |
| Chemo onlyShort-course radiation (SCRT) followed by 6 cycles of mFOLFOX6 as neoadjuvant therapy for patients | Drug | AK104 plus, Chemo only |
Primary outcome
3-year disease free survival (3-y DFS)
Time frame: 3-year
The survival rate of patients without disease recurrence or death due to the disease progression patients at 36 months.
5 secondary outcomes
Pathological complete response rate
Time frame: Up to 6 months
Overall Survival
Time frame: Up to 5 years
Objective Response Rate
Time frame: Up to 6 months
Clinical complete response rate
Time frame: Up to 36 months
Incidence of adverse events
Time frame: Up to 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2025.
- Individual participant dataSharing planned: No
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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.
WA He, Doctor principal investigator
Shenzhen Peolple's Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AK104 plus and Chemo only in people with Rectal Cancer, run by Wan He.
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 14 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 11 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Wan He, Doctor (18823719462, 393322301@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-year disease free survival (3-y DFS) (time frame: 3-year). 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 Mar 2025.