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Locally Advanced Rectal CarcinomaPhase 2NeoCaCRTNCT05792735

Neoadjuvant Cadonilimab Plus Chemotherapy Following Short-Course Radiotherapy in Locally Advanced Rectal Cancer

A Phase 2 study testing Cadonilimab Injection, Short-course radiotherapy and Consolidation chemotherapy in people with Locally Advanced Rectal Carcinoma, run by Shenzhen People's Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The goal of this clinical trial is to test the efficacy and safety in patients with locally advanced middle and lower rectal cancer. The main questions it aims to answer are:• Whether Cadonilimab combined with chemotherapy following short-course radiation can improve pathological complete response(pCR) rate? •Are the… Read more about this study

Who is it for?
Ages 18 to 79 years
Conditions the study is for
Locally Advanced Rectal Carcinoma
What is being tested?
Cadonilimab Injection, Short-course radiotherapy and Consolidation chemotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteChina
Study dates
11 Apr 2023to 31 Jan 2025
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 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 yeas and ≤79 years. The gender is not limited.
  • Histopathology confirmed the diagnosis of rectal adenocarcinoma.
  • Patients with rectal cancer based on endoscopic ultrasound and / or pelvic MRI contrast + contrast, chest CT, head MRI or CT + contrast, or positron emission tomography / computed tomography （PET / CT）, staging criteria per American Joint Committee on Cancer (AJCC) 8th edition cancer stage, cT 3-T4 / N + M0.
  • 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.
  • The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0- 1.
  • Adequate bone marrow and organ function meets the following criteria:
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  • Neutrophil count (ANC)≥1.5×l09/L
  • Platelet (PLT) ≥80×109/L
  • Hemoglobin (Hb) level ≥90 g/L
  • 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

  • Previous history of severe hypersensitivity to other monoclonal antibodies or any component of Cadonilimab.
  • Preoperative pathology was diagnosed as squamous cell carcinoma or neuroendocrine tumor
  • 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).
  • Previous treatment against the PD-1 receptor or its ligand PD-L1 or the cytotoxic T lymphocyte-associated protein-4 (CTLA-4) receptor.
  • History of autoimmune diseases, including but not limited to myasthenia gravis, myositis, 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 glomerulonephritis; 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;
  • Usage of systemic immune activation drugs (including but not limited to interferon or Interleukin-2) within 4 weeks prior to enrollment or within 5 half-lives of the drug (whichever is shorter);
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  • Usage of 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-tumor necrosis factor agents [anti-TNF]) within 2 weeks prior to enrollment. Local, ocular, intra-articular, nasal, and inhaled corticosteroids are permitted;
  • Patients requiring baseline and subsequent MRI tumor evaluation with previous allergic reactions to intravenous contrast agents may use preventive steroids;
  • Allowing the use of inhaled corticosteroids for chronic obstructive pulmonary disease, corticosteroid hydrochloride (e. g., fluorohydrocortisone) in patients with orthostatic hypotension, and low-dose corticosteroid maintenance for adrenal cortical insufficiency.
  • Patients with previous allogeneic bone marrow transplantation or previous solid organ transplantation.
  • 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.
  • 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 (TB) (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).
  • Patients with prior or cured HBV infection (defined as hepatitis B core antibody positive and HBsAg negative) were to be eligible to participate in the study only if HBVDNA was negative (HBVDNA˂ 1000 cps / ml);
  • Patients with positive hepatitis C (HCV) antibody are not eligible for the study only if polymerase chain reaction shows negative HCVRNA;
  • 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).
  • Presence of severe neurological or psychiatric disorders, including dementia and epileptic seizures.
  • The NCI-CTCAE grade 2 peripheral neuropathy.
  • Female patients during pregnancy or lactation.
  • Chronic bowel disease or short bowel syndrome.
  • Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency.
  • 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.
  • 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

1 site in 1 country.

China1 site

  • Shenzhen People's Hospital

    Shenzhen, Guangdong, 518020

Other trials in China

About this study

Official title: A Prospective, Open-Label, Single-Arm and Multicentre Phase II Study to Explore the Efficacy and Safety of Neoadjuvant Cadonilimab Plus Chemotherapy Following Short-Course Radiotherapy in Middle and Lower Locally Advanced Rectal Cancer

The goal of this clinical trial is to test the efficacy and safety in patients with locally advanced middle and lower rectal cancer. The main questions it aims to answer are:• Whether Cadonilimab combined with chemotherapy following short-course radiation can improve pathological complete response(pCR) rate? •Are the toxicities of the combination therapy manageable? Participants will be given radiation of 5 Gy for 5 days and then neoadjuvant Cadonilimab combined with modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) for 6 cycles. Without progressed disease, total mesorectal excision (TME) or transanal local excision will be performed. If clinical complete response was received, watch and wait strategy is one of choices. Adjuvant Cadonilimab plus mFOLFOX6 for another 6 cycles could be suggested for non-pCR participants,while surveillance is also suitable for pCR ones.

Read the detailed description

Long-term synchronous chemoradiation (CRT) with sequential TME is the treatment recommended by current guidelines for locally advanced rectal cancer (LARC). The latest STELLAR study showed that preoperative short-course radiotherapy (SCRT) combined with preoperative chemotherapy is safe and effective and can be used as an alternative to conventional CRT in LARC [1]. In recent years, new therapies blocking immune checkpoints (cytotoxic T lymphocyte-associated molecular protein 4 (CTLA-4), programmed cell death 1 (PD1) and programmed cell death ligand 1 (PD-L1)) have achieved landmark achievements in the field of cancer therapy. Several clinical trials are evaluating the efficacy of a combination of RT and immune checkpoint inhibitors (ICIs) in rectal cancer (NCT02948348, NCT04124601, NCT04558684). The results of the study suggest that radioimmunotherapy is safe and effective in rectal cancer. A number of studies have shown that combined PD-1 and CTLA-4 blockade is associated with a higher response rate whereas more toxicities in multiple tumor types. Cadonilimab is a tetrameric PD-1/CTLA-4 bispecific antibody, based on the Akeso Tetrabody platform. It introduces novel T cell targeting mechanisms of action that may provide an improved therapeutic index and a favorable toxicity profile compared to PD-1 and CTLA-4 combination therapy. The study of SCRT combined with Cadonilimab and chemotherapy in middle and lower LARC has not been reported at home or abroad.

Therefore, this study plans to recruit 27 patients with middle and lower LARC to explore the efficacy and safety of radiation of 5 Gy for 5 days followed by Cadonilimab 6mg/kg plus mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 48 h) every 2 weeks for total 6 cycles preoperatively. The primary endpoint is the pathological complete response (pCR) after surgery. The secondary endpoints consist of a clinical complete response (cCR), major pathological response (MPR), objective response rate (ORR), recurrence-free survival (RFS), overall survival (OS) and safety. Clinical response was evaluated by endoscopy, digital rectal examination and pelvic MRI. Safety was analyzed in all patients who receive at least one dose of treatment. The exploratory endpoint covers the quality of life.

After surgery, non-pCR patients receive adjuvant Cadonilimab combined with mFOLFOX6 for 6 cycles while pCR ones have two options: adjuvant treatment which is the same as the neoadjuvant regimen or observation. As for cCR patients, TME or transanal local excision is one of options while the watch and wait (W\&W) strategy can also be considered especially for ultra-low rectal cancer.

Being tested
Cadonilimab Injection, Short-course radiotherapy, Consolidation chemotherapy
Keywords
Anti-CTLA-4/PD-1 bispecific antibody, Neoadjuvant chemotherapy, Rectal cancer, Short-course radiotherapy
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cadonilimab InjectionDrug

    Also called AK104

    Cadonilimab, an anti-CTLA-4/PD-1 bispecific antibody, at a dose of 6mg/kg is given in combination with chemotherapy every 2 weeks preoperatively and postoperatively.

  • Short-course radiotherapyRadiation

    Also called SCRT

    Preoperative short-course radiotherapy (5x5 Gy)

  • Consolidation chemotherapyDrug

    Also called mFOLFOX6

    Oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 48 h) every 2 weeks for total 6 cycles preoperatively and postoperatively.

Study groups in NCT05792735
Study groupRoleWhat they receive
Cadonilimab groupExperimentalCadonilimab is administrated with 6mg/kg and repeated every 2 weeks.
Receives: Drug: Cadonilimab Injection; Radiation: Short-course radiotherapy; Drug: Consolidation chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathological Complete Response Rate

    The proportion of patients with no tumor cells in the postoperative specimens

    Measured: Up to 6 months

Secondary outcomes (6)

  1. Disease Free Survival Time from the date of treatment administration until the date of the first documented event of: disease recurrence Disease Free Survival

    Time from the date of treatment administration until the date of the first documented event of: disease recurrence following surgery (preferably biopsy proven), or death - whichever occurs first

    Measured: Up to 5 years

  2. Overall Survival

    Overall survival is defined as time from the date of treatment administration until the date of death from any cause.

    Measured: Up to 5 years

  3. Objective Response Rate

    The rate of participants that achieve either a complete response (CR) or a partial response (PR).

    Measured: Up to 6 months

  4. Clinical Complete Response

    Digital examination of rectum and multi-point puncture of colonoscopy indicate no tumor, and ultrasound colonoscopy and tumor markers

    and MRI are normal, which is considered as clinical complete response.

    Measured: Up to 6 months

  5. Major Pathological Response Rate (MPR)

    The proportion of cancer cells in the resected tumors and lymph nodes is less than 10%.

    Measured: Up to 6 months

  6. Number of participants with treatment-related adverse events (TRAE) as assessed by CTCAE v5.0

    Number of patients with AE, TRAE, immune-related AE (irAE), serious adverse event (SAE) assessed by CTCAE v5.0, change from baseline in liver function, kidney function, peripheral blood counts, etc. at 3 months

    Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2023
  2. Study start11 Apr 2023
  3. Primary completion31 Oct 2024
  4. Study completion31 Jan 2025

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
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05792735
Sponsor's protocol ID
Shenzhen CRC-004
Acronym
NeoCaCRT
Status last verified
Feb 2025
First submitted
9 Feb 2023
Last updated
5 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, Liu WY, Chen SL, Li S, Lu NN, Cai Y, Li YH, Zhu Y, Cheng GH, Zhang HY, Wang X, Zhu SY, Wang J, Li GF, Yang JL, Zhang K, Chi Y, Yang L, Zhou HT, Zhou AP, Zou SM, Fang H, Wang SL, Zhang HZ, Wang XS, Wei LC, Wang WL, Liu SX, Gao YH, Li YX. Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR). J Clin Oncol. 2022 May 20;40(15):1681-1692. doi: 10.1200/JCO.21.01667. Epub 2022 Mar 9.

    PubMed 35263150

  • Hodi FS, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Cowey CL, Lao CD, Schadendorf D, Wagstaff J, Dummer R, Ferrucci PF, Smylie M, Hill A, Hogg D, Marquez-Rodas I, Jiang J, Rizzo J, Larkin J, Wolchok JD. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Nov;19(11):1480-1492. doi: 10.1016/S1470-2045(18)30700-9. Epub 2018 Oct 22.

    PubMed 30361170

  • Sharma P, Siefker-Radtke A, de Braud F, Basso U, Calvo E, Bono P, Morse MA, Ascierto PA, Lopez-Martin J, Brossart P, Rohrberg K, Mellado B, Fischer BS, Meadows-Shropshire S, Abdel Saci, Callahan MK, Rosenberg J. Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma: CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results. J Clin Oncol. 2019 Jul 1;37(19):1608-1616. doi: 10.1200/JCO.19.00538. Epub 2019 May 17.

    PubMed 31100038

  • Shamseddine A, Zeidan YH, El Husseini Z, Kreidieh M, Al Darazi M, Turfa R, Kattan J, Khalifeh I, Mukherji D, Temraz S, Alqasem K, Amarin R, Al Awabdeh T, Deeba S, Jamali F, Mohamad I, Elkhaldi M, Daoud F, Al Masri M, Dabous A, Hushki A, Jaber O, Charafeddine M, Geara F. Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma. Radiat Oncol. 2020 Oct 7;15(1):233. doi: 10.1186/s13014-020-01673-6.

    PubMed 33028346

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cadonilimab Injection, Short-course radiotherapy and Consolidation chemotherapy in people with Locally Advanced Rectal Carcinoma, run by Shenzhen People's Hospital 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 15 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: finished, as of the sponsor's last update on 5 Feb 2025. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Pathological Complete Response Rate (time frame: Up to 6 months). 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 NCT05792735, which also lists 4 linked publications.

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 5 Feb 2025; AzTrials last refreshed its copy on 7 Nov 2026.

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