ToripalimabPhase 3NCT05669092
A Phase III Trial of Anus-preservation in Low Rectal Adenocarcinoma Based on MMR/MSI Status
A Phase 3 study testing Toripalimab, CRT and SCRT in people with Toripalimab and Radiation, run by Zhejiang Cancer Hospital at 1 site in China.
Trial summary
pMMR/MSS and 32 dMMR/MSI-H patientspatients were planned to be enrolled. Patients with dMMR/MSI-H will be randomly assigned to the immunotherapy arm or short-course radiotherapy sequential immunotherapy arm; pMMR/MSS patients will receive capecitabine-irinotecan based concurrent radiotherapy before being randomly… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Toripalimab, Radiation
- What is being tested?
- Toripalimab, CRT and SCRT
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 174 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2022to 31 Dec 2025
- Phase
- Phase 3
- 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
- pathological confirmed adenocarcinoma；
- clinical stage T2-4 and/or N+，Not suitable for initial local excision to achieve radical treatment；
- the distance from anal verge less than ≤ 5cm，or surgical evaluation concludes that direct surgical anal preservation is not possible without distance metastases；
- age 18-70 years old, female and male；
- Strong desire for anal preservation and ability to be closely monitored for at least 2 years after chemoradiotherapywith good compliance；
- without distant metastases；
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- ECOG Performance status 0-1；
- Detection of UGT1A1*6 and *28 gene status (for pMMR patients)；
- Sufficient bone marrow reserve and physical capacity to receive consolidation chemotherapy after chemoradiotherapy (for pMMR patients)；
- with good compliance；
- signed the inform consen.
Who cannot join
- pregnant or breastfeeding women；
- Persons with a history of uncontrolled epilepsy, central nervous system disorders, or psychiatric disorders whose clinical severity, as judged by the investigator, may prevent the signing of informed consent or affect the patient's compliance with oral medications；
- Difficult to achieve complete remission at the available level of evidence, such as: tumor largest diameter >10 cm; largest diameter of lateral lymph nodes >2 cm; baseline CEA >= 100; biopsy pathology with an indolent cell carcinoma component; tumor of circumferential narrowing type on anal finger examination, with inclusion decided by the judgment of the evaluation team if necessary；
- Clinically significant (i.e., active) heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmias requiring pharmacological intervention, or a history of myocardial infarction within the last 12 months；
- persons requiring immunosuppressive therapy for organ transplantation；
- Persons with severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases；
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- Subjects with baseline routine blood and biochemical indicators do not meet the following criteria: hemoglobin ≥ 90g/L; absolute neutrophil count (ANC) ≥ 1.5×109/L; platelets ≥ 100×109/L; ALT, AST ≤ 2.5 times the upper limit of normal; ALP ≤ 2.5 times the upper limit of normal; serum total bilirubin < 1.5 times the upper limit of normal; serum creatinine < 1 times the upper limit of normal limit; serum albumin ≥30g/L；
- Known to have dihydropyrimidine dehydrogenase (DPD) deficiency；
- allergic to any investigational drug component.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhengjiang Cancer Hospital
Hangzhou, Zhejiang
JI ZHU, 13501978674, zhuji@zjcc.org.cn
About this study
Official title: A Randomized, Controlled, Open-label, Multicenter, Phase III Trial of Anus-preservation in Low Rectal Adenocarcinoma Based on MMR/MSI Status(APRAM)
pMMR/MSS and 32 dMMR/MSI-H patientspatients were planned to be enrolled. Patients with dMMR/MSI-H will be randomly assigned to the immunotherapy arm or short-course radiotherapy sequential immunotherapy arm; pMMR/MSS patients will receive capecitabine-irinotecan based concurrent radiotherapy before being randomly assigned to the XELIRI or FOLFRINOX arm.
The rate of complete response (sustained cCR for ≥ 1 year), long-term prognosis and adverse effects will be analyzed.
- Conditions
- Toripalimab, Radiation
- Being tested
- Toripalimab, CRT, SCRT, XELIRI, FOLFRINOX
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Also called PD-1inhibitor
3mg/Kg iv d1q2w
CRTRadiation
Also called LCRT
IMRT 50Gy/25fx 625mg/m2 bid d1-5 qw Irinotecan:1、Full wild (GG+6/6): 80mg/m2/week for 5 times 2、Single site mutation (GG+6/7 or GA+6/6): 65mg/m2/week for 5 times 3、Double locus mutation (GG+7/7 or AA+6/6 or GA+6/7): 50mg/m2/week for the 1st, 2nd, 4th and 5th week for 4 times
SCRTRadiation
Also called short-course radiotherapy
25Gy/5fx
XELIRIDrug
Also called Capecitabine and Irinotecan
Capecitabine: 1000mg/m2 bid d1-14 Irinotecan: 200mg/m2 ivgtt d1 q3w
FOLFRINOXDrug
Also called Irinotecan,Oxaliplatin and 5-FU
Irinotecan: 150mg/m2 ivgtt d1 (double locus mutation downregulated to 120mg/m2) Oxaliplatin: 85mg/m2 ivgtt d1 5-FU: 2400mg/m2 ivgtt 46h q2w
| Study group | Role | What they receive |
|---|---|---|
| ARM A: dMMR/MSI-H patients | Experimental | patients will receive 12 cycles of PD-1 antibody Receives: Drug: Toripalimab |
| ARM B: dMMR/MSI-H patients | Experimental | patients will receive 5*5Gy short-course radiotherapy, followed by 12 cycles of PD-1 antibody Receives: Drug: Toripalimab; Radiation: SCRT |
| ARM C: pMMR/MSS patients | Experimental | patients will receive CRT followed by 6 cycles of XELIRI Receives: Radiation: CRT; Drug: XELIRI |
| ARM D: pMMR/MSS patients | Experimental | patients will receive CRT followed by 12 cycles of FOLFRINOX Receives: Radiation: CRT; Drug: FOLFRINOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
complete response (CR) rate.
cCR ≥ 1 year.
Measured: The status of cCR will be evaluated after the completion of neoadjuvant therapy.
Secondary outcomes (6)
adverse effects rate.
CTC 4.0 standard.
Measured: From date of randomization until the date of death from any cause, assessed up to 5 years ] Rate of chemotherapy, radiotherapy and immunotherapy related adverse events.
QoL
Quality of life will be evaluated using EORTC QLQ-C30 score
Measured: From date of randomization until the date of death from any cause, assessed up to 10 years
3 year local recurrence free survival rate
Rate of 3 year local recurrence free survival
Measured: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months. ]
3 year disease free survival rate
Rate of 3 year disease free survival
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months. ]
3 year overall survival rate
Rate of 3 year overall survival
Measured: From date of randomization until the date of death from any cause, assessed up to 36 months.
Organ preservation
TME-free survival
Measured: From date of randomization until the date of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2022
- Study start1 Nov 2022
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ToripalimabStudies of the same condition, open and under way.
- More trials run by Zhejiang Cancer HospitalThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 174 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ji Zhu, Zhejiang Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05669092
- Sponsor's protocol ID
- CARTOnG 2201
- Status last verified
- Dec 2022
- First submitted
- 28 Nov 2022
- Last updated
- 30 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Huang CY, Bai MH, Shen JW, Sun QQ, Feng YR, Chen QP, Mao W, Ju HX, Zhu J. Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial. BMC Cancer. 2024 Jan 10;24(1):57. doi: 10.1186/s12885-024-11829-2.
PubMed 38200410
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled, Open-label, Multicenter, Phase III Trial of Anus-preservation in Low Rectal Adenocarcinoma Based on MMR/MSI Status(APRAM)
- ClinicalTrials.gov ID
- NCT05669092
- Acronym / sponsor ID
- CARTOnG 2201
- Conditions
- Toripalimab, Radiation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 174 participants (estimated)
- Lead sponsor
- Zhejiang Cancer HospitalUniversity, hospital or other
- Study start
- 1 Nov 2022 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 30 Dec 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.
pMMR/MSS and 32 dMMR/MSI-H patientspatients were planned to be enrolled. Patients with dMMR/MSI-H will be randomly assigned to the immunotherapy arm or short-course radiotherapy sequential immunotherapy arm; pMMR/MSS patients will receive capecitabine-irinotecan based concurrent radiotherapy before being randomly assigned to the XELIRI or FOLFRINOX arm.
The rate of complete response (sustained cCR for ≥ 1 year), long-term prognosis and adverse effects will be analyzed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ARM A: dMMR/MSI-H patients | Experimental | Drug: Toripalimabpatients will receive 12 cycles of PD-1 antibody |
| ARM B: dMMR/MSI-H patients | Experimental | Drug: Toripalimab, Radiation: SCRTpatients will receive 5*5Gy short-course radiotherapy, followed by 12 cycles of PD-1 antibody |
| ARM C: pMMR/MSS patients | Experimental | Radiation: CRT, Drug: XELIRIpatients will receive CRT followed by 6 cycles of XELIRI |
| ARM D: pMMR/MSS patients | Experimental | Radiation: CRT, Drug: FOLFRINOXpatients will receive CRT followed by 12 cycles of FOLFRINOX |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- pathological confirmed adenocarcinoma；
- clinical stage T2-4 and/or N+，Not suitable for initial local excision to achieve radical treatment；
- the distance from anal verge less than ≤ 5cm，or surgical evaluation concludes that direct surgical anal preservation is not possible without distance metastases；
- age 18-70 years old, female and male；
- Strong desire for anal preservation and ability to be closely monitored for at least 2 years after chemoradiotherapywith good compliance；
Key exclusion criteria (9 listed)
- pregnant or breastfeeding women；
- Persons with a history of uncontrolled epilepsy, central nervous system disorders, or psychiatric disorders whose clinical severity, as judged by the investigator, may prevent the signing of informed consent or affect the patient's compliance with oral medications；
- Difficult to achieve complete remission at the available level of evidence, such as: tumor largest diameter >10 cm; largest diameter of lateral lymph nodes >2 cm; baseline CEA >= 100; biopsy pathology with an indolent cell carcinoma component; tumor of circumferential narrowing type on anal finger examination, with inclusion decided by the judgment of the evaluation team if necessary；
- Clinically significant (i.e., active) heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmias requiring pharmacological intervention, or a history of myocardial infarction within the last 12 months；
- persons requiring immunosuppressive therapy for organ transplantation；
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 |
|---|---|---|
| ToripalimabAlso: PD-1inhibitor3mg/Kg iv d1q2w | Drug | ARM A: dMMR/MSI-H patients, ARM B: dMMR/MSI-H patients |
| CRTAlso: LCRTIMRT 50Gy/25fx 625mg/m2 bid d1-5 qw Irinotecan:1、Full wild (GG+6/6): 80mg/m2/week for 5 times 2、Single site mutation (GG+6/7 or GA+6/6): 65mg/m2/week for 5 times 3、Double locus mutation (GG+7/7 or AA+6/6 or GA+6/7): 50mg/m2/week for the 1st, 2nd, 4th and 5th week for 4 times | Radiation | ARM C: pMMR/MSS patients, ARM D: pMMR/MSS patients |
| SCRTAlso: short-course radiotherapy25Gy/5fx | Radiation | ARM B: dMMR/MSI-H patients |
| XELIRIAlso: Capecitabine and IrinotecanCapecitabine: 1000mg/m2 bid d1-14 Irinotecan: 200mg/m2 ivgtt d1 q3w | Drug | ARM C: pMMR/MSS patients |
| FOLFRINOXAlso: Irinotecan,Oxaliplatin and 5-FUIrinotecan: 150mg/m2 ivgtt d1 (double locus mutation downregulated to 120mg/m2) Oxaliplatin: 85mg/m2 ivgtt d1 5-FU: 2400mg/m2 ivgtt 46h q2w | Drug | ARM D: pMMR/MSS patients |
Primary outcome
complete response (CR) rate.
Time frame: The status of cCR will be evaluated after the completion of neoadjuvant therapy.
cCR ≥ 1 year.
6 secondary outcomes
adverse effects rate.
Time frame: From date of randomization until the date of death from any cause, assessed up to 5 years ] Rate of chemotherapy, radiotherapy and immunotherapy related adverse events.
QoL
Time frame: From date of randomization until the date of death from any cause, assessed up to 10 years
3 year local recurrence free survival rate
Time frame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months. ]
3 year disease free survival rate
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months. ]
3 year overall survival rate
Time frame: From date of randomization until the date of death from any cause, assessed up to 36 months.
Organ preservation
Time frame: From date of randomization until the date of surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2022.
- Derived from this study: PubMed 38200410Huang CY, Bai MH, Shen JW, Sun QQ, Feng YR, Chen QP, Mao W, Ju HX, Zhu J. Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial. BMC Cancer. 2024 Jan 10;24(1):57. doi: 10.1186/s12885-024-11829-2.
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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 3 study testing Toripalimab, CRT and SCRT in people with Toripalimab and Radiation, run by Zhejiang Cancer 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 11 inclusion and 9 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 30 Dec 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact JI ZHU (13501978674, zhuji@zjcc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
complete response (CR) rate. (time frame: The status of cCR will be evaluated after the completion of neoadjuvant therapy.). 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 NCT05669092, which also lists 1 linked publication.
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 30 Dec 2022.